How To Increase Your Metabolism

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Xpress Fat Loss Workouts Summary


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All the modules inside this e-book are very detailed and explanatory, there is nothing as comprehensive as this guide.

Increased metabolic rate

Under normal conditions, any increase in metabolic CO2 production is usually associated with a proportional increase in VA such that PaCO2 is maintained within the normal limits. However, in patients with severe abnormalities of the control system of breathing and of gas exchange (e.g. severe airway obstruction), hypercapnia may result from relatively small increases in metabolic rate, such as in fever, sepsis, agitation, excessive weight, hyperthyroidism, increased work of breathing, and carbohydrate excess or increased amino acid content due to total parenteral nutrition.

Energy metabolismcaloric needs

However, when indirect calorimetry is not available, an equation must be used to estimate energy expenditure. It is important to avoid both underfeeding and overfeeding in the critically injured patient. Hart recommended an energy intake of 1.2 times measured resting metabolic rate (22). The resting metabolic rate in critically ill patients is higher than that of a healthy individual, even one with a wound. Therefore, energy needs of the critically ill should be separated from those of the healthy individual. Examples of equations that can be used to predict the energy expenditures of critically ill patients are found in Table 2.1 (26-28).

Metabolic response to stress

Compared with the starving patient, the critically ill patient has a very different 'internal milieu' and exhibits greater and more prolonged negative nitrogen balance due to protein breakdown (gluconeogenesis). There is no adaptation to energy production from fat stores, and the basal metabolic rate is increased by 20 to 80 per cent. Metabolic and endocrine responses include stimulation of the sympathetic nervous system, release of epinephrine (adrenaline), glucocorticoids, and glucagon, suppression of prolactin, growth hormone, and thyroid hormone release, metabolic resistance to the effects of insulin, production of cytokine mediators, and release of eicosanoid precursors from membrane-bound phospholipids (Fig 1).

Fat metabolism in the healing wound

The need for proper nutrition to facilitate wound healing is a well-established paradigm in medicine.72-79 However, an understanding of the molecular, biochemical, and cellular processes that occur during wound healing is complicated by the fact that there are multiple types of both acute and chronic wounds. Acute wounds (e.g., surgical, trauma, or burns) require a different treatment regimen than chronic wounds (e.g., venous, pressure, or diabetic ulcers). Moreover, individuals with chronic wounds often have underlying disease or complicating factors that present additional challenges to healing (e.g., diabetes, obesity, frail geriatric patients). Although we have a good level of understanding about the effects of wounds on whole body energy metabolism, this data cannot be directly extrapolated to metabolism in the wound. The reason for this is that the wound functions within its own metabolic microenvironment. Tissue blood flow (perfusion) and oxygen tension may be lower than...

Energy Metabolism in Anaerobically Functioning Mitochondria

Flavoprotein Oxidation

The other class of anaerobic mitochondria, those which use fermentation reactions, is present in organisms that are highly adapted for either prolonged survival or continuous functioning in the absence of oxygen, such as parasitic helminths, or in organisms that are adapted to alternating periods in the presence and absence of oxygen, such as mussels, oysters and lugworms, which are intermittently dependent on this process when the tides of the sea force them to function anaerobically (De Zwaan 1991 Grieshaber et al. 1994). The energy metabolism in these anaerobic mitochondria differs principally and significantly from that in aerobic mitochondria, as no external final electron acceptors are used. Therefore, this mitochondrial metabolism has to be truly fermentative, in other words the number of NADH-producing reactions has to equal the number of NADH-consuming reactions without the use of oxygen or other external electron acceptors. Many mitochondrial catabolic pathways produce NADH,...

Carbohydrates energy metabolism and wound healing

In general, calories are needed to supply the energy that is necessary for wound healing. Nutritional support generally includes some form of carbohydrates (parenteral dextrose, and enteral lactose, oligosaccharides, etc.). Glucose is a critical nutrient, especially in patients who have experienced significant trauma, such as a burn, as it is required for cellular growth, fibroblastic mobility, and leukocyte activity. As the metabolic rate increases, there is a concomitant increase in the conversion of amino acids to glucose and an increased rate of hepatic gluconeogenesis if adequate carbohydrate substrates are not provided.

NAA in Neuronal Energy Metabolism

The first report that NAA might be involved in brain metabolism was by Buniatian and coworkers in 1965.18 The idea that NAA is involved in energy metabolism in the nervous system is based on a number of facts, including that 1) NAA is synthesized by aspartate N-acetyltransferase in neuronal mitochondria19,20, 2) traumatic brain injury causes rapid and partially reversible decreases in NAA concentrations,21-23 3) inhibition of mitochondrial respiration results in the simultaneous decrease of NAA production, ATP production and oxygen consumption in isolated brain mitochondria,24 and 4) NAA levels in the striatum of rats and primates were significantly decreased after the animals were treated with a mitochondrial toxin (3-ntiroproprionate).25 Recently, Madhavarao and coworkers proposed a model whereby NAA is associated with neuronal energy production (see Namboodiri et al. and Madhavarao and Namboodiri, this volume). In this model, aspartate aminotransferase, the enzyme that synthesizes...

Carbohydrate and fat metabolism

The glucose-fatty acid cycle refers to important metabolic interactions between glucose and fat metabolism (Box 6.4). These interactions occur in adipose tissue and in muscle the endocrine pancreas is involved via insulin secretion. They were first observed in rat heart muscle, but there is now considerable evidence that they occur in skeletal muscle in humans. The glucose-fatty acid cycle is not a metabolic cycle in the normal sense - it does not involve the interconversion of glucose and fatty acids - but a series of metabolic regulatory events that coordinate glucose and fat metabolism under normal and some abnormal conditions.

Nutrition and the metabolic response to injury

Ebb Phase Medical Definition

Cuthbertson described the metabolic response to injury as consisting of an ebb phase and a flow phase.2526 The ebb phase is the period of traumatic shock or hypometabolism during the first few hours or days after injury. This phase is soon replaced by the flow phase that is a period of hypermetabolism that may last for weeks or months depending on the nature of the injury and obstacles to recovery. In the case of minor injury, such as elective surgery, both of these phases may be relatively brief and of minor magnitude. In the case of multiple trauma or large percent body surface area burns, both ebb and flow may be of maximum magnitude and duration. In this latter group of patients, nutritional support becomes critical, because the potential to deplete the body's nutrient reserves is high. On the contrary, in a patient of good preoperative nutritional status undergoing routine elective surgery, it is unlikely that perioperative nutritional support will have a measurable effect on...

Polyunsaturated fatty acids on energy metabolism and other factors connected to weight control

The mechanism behind the benefits of omega-3 PUFAs on energy metabolism is at present not completely understood. There are, however, many possibilities since these fatty acids have many different roles in a cell. For example, apart from being an energy source, fatty acids build up the cellular membranes, regulate gene expression and function as signalling molecules and as precursors for complex biologically active molecules such as, for example, eicosanoids (Simopoulos, 1999, Ruxton et al., 2004). Since omega-3 PUFAs exert positive effects in many different diseases there have been implications for a common pathway for the effects. One mechanism that has been presented is the ability of omega-3 PUFAs to affect the biochemical composition of biological membranes (Ma et al., 2004). Indeed, the cellular fatty acids composition is a mirror of the ingested types of fatty acids. Incorporation of PUFAs into lipid membranes results in altered interaction between the lipids and the membrane...

Current concepts of cerebral oxygen transport and energy metabolism after severe traumatic brain injury

Abstract Before energy metabolism can take place, brain cells must be supplied with oxygen and glucose. Only then, in combination with normal mitochondrial function, sufficient energy (adenosine tri-phosphate (ATP)) can be produced. Glucose is virtually the sole fuel for the human brain. The brain lacks fuel stores and requires a continuous supply of glucose and oxygen. Therefore, continuous cerebral blood flow (CBF), cerebral oxygen tension and delivery, and normal mitochondrial function are of vital importance for the maintenance of brain function and tissue viability. This review focuses on three main issues (1) Cerebral oxygen transport (CBF, and oxygen partial pressure (PO2) and delivery to the brain) (2) Energy metabolism (glycolysis, mitochondrial function citric acid cycle and oxidative phosphorylation) and (3) The role of the above in the pathophysiology of severe head injury. Basic understanding of these issues in the normal as well as in the traumatized brain is essential...

Allometric Scaling of Metabolic Rate and Complexity

The answer is yes the scaling of metabolic rate with size (Kleiber 1961). Allometric scaling laws in biology have undergone a renaissance in interest since West et al. (1997) proposed a fractal model to explain the 'three quarters law' of metabolism, the apparent scaling of metabolic rate with mass to the power of 3 4 across an extraordinary 27 orders of magnitude, from respiratory complexes within mitochondria to the blue whale. In essence, the fractal model argues that metabolic rate is determined by the fractal properties of the supply network, i.e. fractal geometry constrains energy metabolism (West et al. 1997, 1999, 2002 Weibel 2002). This theory has been criticised from various points of view (Lane 2005), notably (1) three-quarter scaling is an illusion in fact metabolic rate more commonly scales with m2 3, where m is mass (Heusner 1991 Dodds et al. 2001 White and Seymour 2003) (2) the theory predicts that the fractal supply network constrains the resting metabolic rate,...

Diseases of Mitochondrial Energy Metabolism and Substrate Selection

Thirty years ago, it was thought that the pathways of mitochondrial energy metabolism were so fundamental that no severe impairment of these pathways was compatible with life. In the last 20 years, diseases specific to mutations within mitochondrial diseases have been recognized (34). In general, these specific diseases of mitochondrial metabolism are rare. Within the last decade it has been proposed that some very common complex diseases result from disordered mitochon-drial energy metabolism, including those caused by disordered substrate utilization. It has recently been reported that the hearts of individuals with type II diabetes, which appear normal in most measurable parameters, have a lowered PCr ATP ratio indicative of a low AG' of ATP hydrolysis that can be correlated with the levels of circulating free fatty acids (35). Others have presented evidence that common neurodegenerative diseases such as Parkinson's and Alzheimer's diseases result from specific defects in...

Fat metabolism during endurance exercise

Thus, fat metabolism during high-intensity endurance exercise does not follow the rules we might expect on the basis of everything we know about human metabolism. The contribution of fatty acids is limited and the availability of glycogen limits the time for which high-intensity exercise can be maintained. We may speculate that perhaps the ability to run at high intensity for long periods was not important in terms of the evolution of Homo sapiens. Maybe the ability to sprint, to escape from a predator, was more important.

Mechanisms calcium and the regulation of energy metabolism

According to Zemel's hypothesis, consumption of relatively large amounts of dietary calcium increases circulating Ca2+ and decreases counter-regulatory serum concentrations of the calcitropic hormones PTH and, as a consequence, vitamin D (calcitriol, 1,25-dihydroxy-vitamin D3). Calcitriol increases intracellular Ca2+ in cultured human adipocytes when added to the cell-culture medium. This means for the above-mentioned metabolic steps, that the decreased serum calcitriol in turn down-regulates Ca2+ influx into adipocytes and thereby reduces intracellular Ca2+ (Fujita and Palmieri, 2000, Palmieri et al., 1998, Shi et al., 2001, Zemel et al., 2000). Intracellular calcium is involved in the regulation of several key enzymes of fat and energy metabolism, including fatty acid synthase. Decreased adipocyte intracellular Ca2+ thereby stimulates lipolysis, fatty acid oxidation (Melanson et al., 2003) and in some studies the expression of uncoupling protein 2 and thereby thermogenesis....

Pathophysiology and metabolic response to injury and stress

As described originally by Cuthbertson 5 , the metabolic response to injury includes an immediate shock or ebb phase and is associated with decreased intravascular volume, reduced tissue perfusion, low cardiac output, and relative hypometabolism, where total oxygen consumption is below normal levels 6 . Profound hypovolemia during this stage of injury may predispose or prime such patients for exacerbated hemodynamic and metabolic responses to subsequent injury after a second insult, such as endotoxemia, surgery, or further hypovolemia 7 .

Spectroscopic imaging through MR Possibilities to be fully tapped for clinical oncology

1 FDG 18F-deoxy glucose is a glucose analogue which is phosphorylated by hexokinase (the first enzyme of the glycolytic pathway) to FDG-6-PO4 and remains trapped intra-cellularly, thus reflecting glycolysis throughout the body. Since many tumor cells have a high metabolic rate mainly via the glycolytic pathway, FDG uptake has been used as a marker of malignancy.

Comments On Metal Ions In Neurology

The brain has the highest metabolic rate of any tissue and has an obligate requirement for aerobic metabolism. This, combined with endogenously high concentrations of Cu and Fe, increase the vulnerability of brain gray matter to radical attack when metal chaperoning is less than perfect. Redox-active metals become available for ROS and radical generation when they either escape their chaperones (usually because the concentration of metal is too high to be completely chaperoned), or because of an accumulation of a damaged metalloprotein that inappropriately permits reaction of the metal with oxygen (Figure 1). Some metal ions like Hg(II), Cd(II), Pb(II), and Al(III) do not subserve physiological purposes, and accumulate in neurons where the high metabolic rate and oxygen requirement of the tissue make toxic exposure to these metals likely to exhibit a neurological phenotype.

Abnormal mechanical load Elastic load

This load, which acts as an inspiratory threshold load, is probably the most important factor leading to acute ventilatory failure in patients with chronic obstructive lung disease because it is associated with decreased inspiratory muscle strength due to pulmonary hyperinflation, increased airway resistance and physiological VD due to ventilation-perfusion mismatch, and increased metabolic rate due to increased work of breathing. In addition, the increased PaCO2 and decreased pH may themselves reduce the inspiratory muscle strength. Furthermore, in chronic obstructive lung disease there is a decreased ventilatory response to CO 2.

Internal and External Proteotoxic Stresses in Mammalian Cells

(DSC) (Lepockal. 1990,1993) and electron spin resonance (Burgman and Kon-ings 1992). Subsequent to this protein denaturation, proteins will aggregate, and a tight relation between heat-induced protein aggregation and the cell biological consequences of heat has been found (Kampinga, 1993). However, many other forms of stress such as arsenite treatment, treatment with amino acid analogs, or oxidative stress can induce (different types of) toxic protein damage. It is important to note that all forms of stress that cause some kind of protein damage also induce the heat shock response, i.e., the activation of the heat shock factor-1 that transactivates the heat-inducible chaperones (Morimoto 1998). Moreover, the induction of chaperones by one proteotoxic stress generally not only results in a transient resistance against the subsequent similar stress, but also results in cross-resistance to many, if not all, other proteotoxic stresses (Hahn and Li, 1982). In general the induced synthesis...

NAA as Acetate Carrier for Myelin Lipid Synthesis

It is important to state that the acetate-lipid synthesis hypothesis does not address the presence of the extraordinarily high levels of NAA in adult neurons. A theory that pertains directly to the high concentrations of NAA in the neurons of adult animals posits that NAA is intimately involved in neuronal energy metabolism.

Basic Physiology of Obesity

Before the body stores excess calories as triglycerides, it tries to use the ingested calories as energy. It does this in three ways basal metabolic rate (BMR), thermogenesis, and physical activity 26 . Like the idling of an engine, the basal metabolic rate is the body's constant conversion on the cellular level of ATP to ADP for energy. This continuous utilization of energy accounts for 70 of the body's daily caloric expenditure. BMR is influenced by thyroid conditions. BMR slows with hypothyroid and increases with hyperthyroid conditions. Consequently, people with hypothyroidism are often obese because of a slow metabolism, and people with hyperthyroidism are commonly thin.

The Concept of Conditional Essentiality

Plasma and tissue carnitine concentrations are lower in newborn infants than in adults, but this condition has not been associated with any physiologic defect. In infants maintained on TPN without carnitine, however, plasma and tissue carnitine levels are low, and in one study, this was associated with impaired fat metabolism and reduced nitrogen retention, both corrected by carnitine supplementation. Hoppel ( 21) concluded from a comprehensive review of the evidence that carnitine may be conditionally essential for premature infants maintained on TPN but is not conditionally essential for adults.

Volume Transmission and Wiring Transmission

Cellular chain (wire), while transmission by VT consists of a three-dimensional diffusion of signals in the extracellular fluid for distances larger than the synap-tic cleft. Transmission by WT thus exhibits (like classic synaptic transmission) a one-to-one ratio with respect to the number of signal source structures and the number of signal targets, whereas transmission by VT shows a one-to-many ratio. With respect to the neuroactive substances and their function in brain tissues, as described above, neurotransmitters as well as neuromodulators convey both modes of function. In fact, it is now generally believed that there exists in the brain some kind of non-synaptic, hormone-like, modulatory transmission besides synaptic transmission. This concept is supported by recent findings of the neurotrophic effects of some neuropeptides and neurotrophins. Furthermore, data on gaseous transmitters like NO have given strong support to this view. For instance NO, once released, can affect the...

Perioperative Brain Protection

The means by which it may be possible to protect the brain from ischemia are pharmacological or physical. Direct pharmacological interventions have focused on drugs that reduce the cerebral metabolic rate (and therefore reduce the demand for oxygen and energy substrate) and on agents that block the cellular mediators of ischemic injury (including calcium influx and the production of destructive protein There is evidence that mild hypothermia has a cerebral protective effect that exceeds that of the barbiturates and which is out of proportion to the degree to which the cerebral metabolic rate is lowered 18 . Profound hypothermia during total circulatory arrest has been shown to be remarkably protective on gross measurement of outcome 19 . Animal studies suggest that prolonged periods of arrest (> 70 min) may be associated with damage to Purkinje's cells of the cerebellum 20 however, the technique may allow procedures to be performed that would be otherwise impossible.

Indirect Measures of Neuronal Output

Functional neuroimaging studies in a patient with temporal lobe epilepsy. A. Imaging performed between seizures and at quiet rest. A PET fluorodeoxyglucose study shows large area of glucose hypometabolism (low metabolism) in an axial image through the left temporal lobe (enclosed by broken circle) B. SPECT 99Tc-HMPAO studies show the blood flow profile during a seizure. Now the same region in the temporal lobe shows a large increase in blood flow, or hyperperfusion, during the seizure, which at the point in time of the injection of tracer is largely confined to the left temporal lobe (enclosed by broken circle). Figure 10. Functional neuroimaging studies in a patient with temporal lobe epilepsy. A. Imaging performed between seizures and at quiet rest. A PET fluorodeoxyglucose study shows large area of glucose hypometabolism (low metabolism) in an axial image through the left temporal lobe (enclosed by broken circle) B. SPECT 99Tc-HMPAO studies show the blood flow profile...

Membrane Complexes Found Only in Desulfovibrio spp

Desulfovibrio spp. are characterized by a high content of periplasmic or membrane-associated cytochromes c (Matias et al. 2005 Pereira and Xavier 2005). Of these, the tetraheme TpIc3 is very abundant, suggesting an important role in energy metabolism. It is thus somewhat surprising that neither Dt. psychrophila nor A. fulgidus have a TpIc3 (and indeed have very few cytochromes c), showing that it is not essential for sulfate reduction. In Desulfovibrio spp. the pool of periplasmic cytochromes c act as electron acceptors for periplasmic hydrogenases and formate dehydrogenases (Heidelberg et al. 2004 Elantak et al. 2005 Matias et al. 2005). In these organisms the two classes of proteins lack the cytochrome b membrane subunit typically present in such enzymes (Pereira et al. 2007). Dt. psychrophila and A. fulgidus have hydrogenases and formate dehydrogenases with a cytochrome b membrane subunit, which transfers electrons to the menaquinone pool. In Desulfovibrio organisms the electrons...

Monitoring of Cerebral Blood Flow

Kety-Schmidt Technique The gold standard for global CBF measurement is the Kety-Schmidt technique of nitrous oxide washin. Although first described in 1945, the technique remains valid today. It measures global hemispheric blood flow, necessitates cannulation of the jugular bulb, thus allowing derivation of cerebral metabolic rate for oxygen, and can be performed at bedside.

Oxidative stress OS and formation of free radicals

The AD brain, including the generation of free radicals, and leading to oxidative damage in neurons from AD, its cell, and tg mouse models (86). Among the various free radicals generated in the living organism, hydroxyl radical and peroxynitrite are the most potent and can damage cells via non-selective oxidation of proteins, lipids, fatty acids, and nucleic acid (87-89). They are formed via the Haber-Weiss and Fenton reaction between H2O2 and reduced transition metals (usually iron II or copper) (see (90) for review). Proteins are initial targets of ROS, and protein radicals generated by ROS can oxidize GSH, suggesting that radicals are important for oxidative stress (91). In AD, aberrant metal homeostasis may contribute to the formation of ROS and toxic AP oligomers, thus, facilitating the formation of amyloid plaques (92). Alternatively, not superoxide itself but the protoneated form, the hydroxyl radical, can initiate lipid peroxidation reactions. Another mechanism of lipid...

Biochemical and Evolutionary Aspects of Eukaryotes That Inhabit Sulfidic Environments

Abstract Various eukaryotes inhabit environments that harbor high concentrations of sulfide, which is a potent inhibitor of complex IV in the mitochondrial respiratory chain. They must therefore posses means by which they can detoxify sulfide, or use alternative electron routes that circumvent oxygen as the terminal acceptor, or both. The biochemical mechanisms through which eukaryotes deal with sulfide are beginning to come into focus, with sulfide quinone oxidoreductase and the energy metabolism germane to anaerobic mitochondria standing in the foreground. This chapter briefly covers current progress in understanding the biochemistry of sulfide detoxification and utilization by eukaryotes. In light of newer views of ocean geochemistry (Canfield oceans), both the anaerobic biochemistry of mitochondria and their capacity to deal with sulfide are most easily interpreted as evolutionary holdovers from the anoxic and sulfidic phase of ocean history between about 2.3 billion and about 0.6...

Physiology Of Exercise

In people without diabetes, a precise endocrine response ensures that the energy needs of the exercising muscle are met and glucose homeostasis is maintained. This metabolic response is ameliorated in Type 2 diabetes and lost in Type 1 diabetes and the challenge is to reproduce the physiological state of the non-diabetic individual. A brief review of the metabolic, hormonal and physiological responses to exercise is given below. Metabolic changes provide the energy required for exercise. Glucose uptake by exercising muscle increases and at the onset of exercise, muscle glycogen is converted to lactate to provide the energy substrate. When muscle glycogen is exhausted, energy is provided by glucose from the liver following glycogen-olysis and eventually from metabolism of free fatty acids in adipose tissue. The metabolic response depends on a number of factors People with Type 2 diabetes usually have sufficient circulating insulin to precipitate the normal metabolic response to...

Hypoxia Inducible Factor

There are several proteins that belong to the hypoxia inducible factor (HIF) family. In addition, HIF is thought to function in both cytoprotection and the pathophysiology of several diseases 97,98 . This section will focus specifically on HIF-1 and its role in cytoprotection. HIF-1 is a heterodimeric transcription factor containing the subunits HIF-1 a and HIF-1(3 97,98 , In the context of this chapter, HIF-1 can be thought of as a major regulator of genes necessary for adaptation to hypoxia. The list of genes thought to be dependent on HIF-1 include genes for vascularization 99 , energy metabolism 100 , vascular tone 101 , and erythropoiesis 102 (Table II). In addition, haem oxygenase-1 expression is, in part, dependent on HIF-1 activity 103 ,

Treatment of hypotension in the flow phase

Immediately post-shock, most patients have an elevated O2 requirement because of the need to repay the O2 debt that developed previously. Subsequently, traumatic and septic shock patients usually demonstrate ongoing elevations in tissue O 2 requirement since the metabolic rate is elevated by the healing processes in trauma and the generalized inflammation typical of sepsis. These patients may then need a systemic O 2 delivery above the normal range (> 600 ml min m2). Increasing O2 delivery is accomplished by keeping PaO2 above 70 mmHg (9.3 kPa), transfusing packed red cells to correct anemia, and increasing cardiac output with fluid therapy, inotropes, and or dilators. A right heart catheter may now be necessary to guide management. Left ventricular filling is optimized by additional fluids. If the pulmonary artery wedge pressure is above 15 to 18 mmHg, O2 delivery is increased using vasodilators and inotropes. An increase in SvO2 and a decrease in arterial lactate can be used to...

Models of aSynucleinopathy

Many overexpression models of wild type and mutant a-synuclein have been created in cells, worms, flies, mice, and rats (71-76). In general these studies show that transgenic overproduction of a-synuclein causes neurotoxicity, whereas its ablation is not associated with neuropathology (54,77). Human genetic studies in dominant families highlight a toxic gain-of-function (28,29,35). Mice demonstrate a variety of neuropathologic changes, including neuronal atrophy, dystrophic neurites, and astrocytosis, accompanied by a-synuclein positive Lewy body-like inclusions, with no abnormal accumulation of a-synuclein in spinal cord or glial cells (71,74,78). In contrast to other species, murine dopaminergic neurons in vivo appear resistant to a-synuclein-induced neurotoxicity (71,79). Paradoxically, tyrosine hydroxylase-positive neurons in primary cultures do show selective vulnerability to a-synuclein overexpression. Viral delivery methods within the substantia nigra of adult rats also results...

Evolution and Ecology of Microbes Dissimilating Sulfur Compounds Insights from Siroheme Sulfite Reductases

Abstract Sulfur microorganisms have been thriving on Earth since the dawn of life and are still of central importance for the functioning of modern ecosystems. Here, we summarize the current perception of the evolution of dissimilatory siro-heme sulfite reductases (DSRs), antique key enzymes in the energy metabolism of sulfur microbes. We further give recent examples of the diversity and ecology of uncultured sulfur-dissimilating microorganisms unprecedented insights that were only made possible by exploiting DSR-encoding genes as molecular markers in environmental surveys.

Diet And Heart Failure

Finally, it has been shown that up to 50 of patients suffering from CHF are malnourished to some degree45 and CHF is often associated with weight loss. The weight loss may be associated with multiple etiologies,46 in particular, the lack of activity resulting in loss of muscle bulk and increased resting metabolic rate. Another factor is a shift toward catabolism with insulin resistance and increased catabolic activity relative to anabolic steroids.47 Tumor necrosis factor (TNF), sometimes called cachectin, is higher in many patients with CHF and may explain their weight losses. Interestingly, there is a positive correlation between TNF and markers of oxidative stress in a failing heart,48 suggesting a link between TNF and antioxidant defenses in CHF (the potential importance of TNF in CHF is discussed in Section 4.3.2). Finally, cardiac cachexia is a well-recognized complication of CHF. Its prevalence increases as symptoms worsen49 and it is an independent predictor of mortality in...

Metabolic function and detoxification

The liver receives the effluent of the splanchnic circulation and is located directly upstream from the pulmonary circulation and cardiac pump, an arrangement adapted to its involvement in metabolic and detoxification functions. The liver is the main site of protein synthesis, for example albumin, which is a key element in maintaining oncotic pressure, and a site of binding for numerous hormones and drugs. It also synthesizes coagulation factors, which may (e.g. factors II, VII, IX, X) or may not (factors V, XI, XII, XIII, and fibrinogen) be dependent on vitamin K. The liver is essential for carbohydrate metabolism by increasing glycogen synthesis when the serum glucose concentration is high, and by degrading glycogen or converting amino acids to glucose by gluconeogenesis when serum glucose concentration is low. With regard to fat metabolism, the liver is responsible for both chylomicron degradation via acetyl-coenzyme A and lipoprotein synthesis during which fatty acids are...

Overview of nutrition and thermogenesis

Total body energy expenditure represents the conversion of oxygen and food (or stored forms of energy) to carbon dioxide, water, biological work and heat, the production of which is inherent to net biochemical reactions in energy metabolism. Energy expenditure at rest can be measured directly as heat produced, hence the term thermogenesis, or indirectly as the amount of oxygen consumed. Total energy expenditure can be broken down into three components (a) obligatory energy expenditure required for normal functioning of cells and organs (represented by the basal metabolic rate, which is defined as the amount of energy expended when an adult organism is awake but resting, not actively digesting food and at thermoneutrality) (b) physical activity (c) adaptive thermogenesis, which is physiologically regulated and is usually defined operationally as heat production in response to environmental factors including temperature and diet. Adaptive thermogenesis has received a lot of attention in...

Experimental models exploring metabolic processes in skin and whole body In Vivo

These studies provided strong evidence that whole body nutritional status has significant impact on skin collagen metabolism and, hence, the healing process of the wound. They support the clinical observations that improving whole body protein nutritional status accelerates the wound healing process in severely burned patients and other surgical patients. It should be noted that, because 18OH-hydroxyproline does not reincorporate into collagen after this amino acid is released from collagen degradation, scientifically, the 18O inhalation method has provided the most accurate estimate of collagen metabolism. Other approaches to label collagen using either 2H -or 13C proline as probes always underestimated the rate of collagen metabolism due to the fact that proline can be released and reincorporated into collagen proteins. In Molnar's study, the simultaneous use of 18O2 and 2H2 proline tracers revealed that the underestimate could be 44 . So far, the 18O2 method is the most accurate...

SqJpyMMM I Op Mrtt Wtfftl UWIift Table 1 Basic medical management of severe acute pancreatitis

Aggressive nutritional support has become standard therapy, since constant features of severe acute pancreatitis include the inability of the gastrointestinal tract to function effectively for long periods and a concurrent increase in the basal metabolic rate caused by the inflammatory process. In addition, there is a high prevalence of premorbid nutritional depletion. The impact on the primary disease process by suppressing pancreatic secretion with total parenteral nutrition remains controversial and probably of little concern. Nutritional support should be initiated early in the course of the attack this may be given parenterally as intravenous substrate infusions including fat emulsions do not stimulate exocrine pancreatic secretion. Lipids are usually well tolerated and contribute towards the caloric substrate needed to meet the increased energy needs of these glucose-intolerant patients. However, intravenous lipid solutions should not be given to either the rare patient with...

Intracranial Pressure Management

Barbiturates are a second-line agent for the management of elevated ICP. Their efficacy in this role remains controversial. The mechanism of action is believed to be their ability to modulate cerebral metabolism and therefore CBF. Barbiturates appear to act as cerebral vasoconstrictors, thus reducing intracerebral blood volume and lowering ICP. Barbiturates also appear to preferentially vasoconstrict normal cerebral blood vessels and increase CBF to relatively ischemic areas. Finally, barbiturates decrease CMRO2, i.e. the cerebral metabolic rate and oxygen consumption. Decreases in CMRO2 appear to result in decreased ICP. A burst-suppression EEG pattern (so-called barbiturate coma) is often required to achieve a maximal decrease in CMRO2. This effect, however, does not come without a significant price. Large doses of barbiturates may cause systemic hypotension and act as negative inotropes, both of which act to decrease cardiac output and, ultimately, CPP in the setting of elevated...

Regulation of Membrane Associated Fatty Acid Transporter Expression

Extensive studies examining the effect of diet on the levels of putative membrane transporters have not yet been published. Studies employing whole animal models, however, have provided some information regarding overall regulation of these proteins. For example, FABPpm expression is markedly elevated in the white adipose tissue of Zucker diabetic and obese (fa fa) rats.62 These rats have lost insulin sensitivity and therefore an increased level of FABPpm mRNA in these animals indicates insulin is a negative regulator of FABPpm expression. The insulin effect in these animals appears to be tissue sensitive, as there was no difference in FABPpm levels in the liver of these rats.62 No information regarding the presence or absence of an insulin-responsive element (IRE) upstream of the FABPpm coding region is available to date. FABPpm levels are also affected by the FA utilization requirements of the tissue. FABPpm levels have been shown to increase in oxidative skeletal muscle during...

Absorption and Metabolism

Studies with homogenized lung tissues show that the alveolated parts generally have higher metabolic rates than the tracheobronchial tissue 142,143 . These studies are not directly relevant, though, to the effect of a drug deposited for local activity on the respiratory lumen. On the other hand, this information is more directly pertinent to drugs intended for systemic effects. Interestingly, the bronchial circulation was shown to have a lower metabolic capacity than the pulmonary circulation 144 . There does not appear to be any clinical evidence, though, that drugs absorbed from the central airways would be metabolized to a lesser extent than following absorption from the lung periphery.

Leptin And Central Nervous System

Although much of the current focus on leptin is as an anti-obesity hormone, accumulating evidence indicates that additional (and more important) biologic roles for leptin are preventing the excess deposition of triglyceride in nonadipose tissue24 and signalling reduced nutrient availability.25 Many of the hypothalamic neurons expressing LRb are regulated by starvation and are responsive to leptin administration.26 One key set of neurons in the medial ARC synthesizes both neuropeptide Y (NPY) and agouti-related protein (AgRP) and projects within the hypothalamus to the PVN, DMH, and LHA.23 26 27 AgRP and NPY are both up-regulated by negative energy balance, and stimulate increased food intake and reduced metabolic rate upon exogenous administration. Leptin infusion inhibits starvation-induced activation of NPY and AgRP gene expression.28

Observed in Certain Categories of Patients

Low GI diets were also found to have beneficial effects on plasma lipids. In two well-controlled studies in type-2 diabetic subjects 12, 13 , there was a reduction of LDL cholesterol and an improvement of the capacity for fibrinolysis (PAI-1) with a low GI diet compared with a high GI diet. Plasma free fatty acids were also found to be lowered by low GI diet 13 . These metabolic effects would be predicted to promote insulin sensitivity and to reduce the risk of CVD.

Energy Requirements In Pregnancy

Pregnancy is an anabolic state requiring energy for the products of conception, the foetal-placental unit and the increase in maternal tissues. Newly synthesised maternal tissues account for a 15-26 increase in metabolic rate in pregnancy (26). The total calculated energy cost for pregnancy is around 355 640 kJ (85 000 kcal) and this translates into an extra 1191.3 kJ (285kcal) a day (27,28). These theoretical energy costs, originally derived in the 1960s by Hytten and Leitch, have been confirmed by more recent physiological measurements (29).

Using ergogenic aids for weight control

A comprehensive definition of the use of nutritional ergogenic aids is 'dietary manipulation to improve physical and sports performance'. Nutritional ergogenic aids are a growing market and are increasing in popularity and variety. There are a large number of products marketed as nutrititional ergogenic aids that also claim to assist in weight management, by virtue of a purported capability to affect some aspects of energy metabolism or, more often, body composition, increasing lean body (muscle) mass and or reducing fat mass. These include protein and amino acid supplements, and combinations of ephedrine and caffeine, already presented in the preceding section. Caffeine has been proven to have ergogenic effects in a number of human studies, although the mechanism(s) behind these effects are largely unknown the popular view is that caffeine, by virtue of its capability to inhibit cAMP phosphodiesterases, increases fat supply to the muscle, which in turn can increase fat oxidation,...

Proteomics of A ferrooxidans Grown in Sulfur Compounds

19859 proteins differentially expressed when grown in metal sulfides, thiosulfate, elemental sulfur, and ferrous iron media were characterized by using 2D PAGE (Ramirez et al. 2004). N-terminal amino acid sequencing and tandem mass spec-trometry analysis of these proteins allowed the identification and localization of their corresponding genes in the available genomic sequence of A. ferrooxidans ATCC 23270. The genomic context around several of these genes suggests their involvement in the energy metabolism of A. ferrooxidans. Two groups of proteins could be distinguished. Proteins highly upregulated by growth on sulfur compounds but downregulated by growth on ferrous iron are particularly interesting, such as a

Chromium and chromium picolinate

Chromium is an essential trace mineral and cofactor to insulin. Chromium picolinate is an organic compound of trivalent chromium and picolinic acid (a naturally occurring derivative of tryptophan), which is better absorbed than dietary chromium. Reported effects of chromium in connection with body weight management found in some clinical trials include an increase in lean body mass, a decrease in percentage body fat and an increase in basal metabolic rate (reviewed in reference 182). However, there is no conclusive evidence of positive effects of chromium supplementation on body composition of healthy humans, even when taken in combination with an exercise training program.213 A 2003 meta-analysis of ten randomized, double-blind, placebo-controlled studies assessing chromium picolinate supplementation without energy restriction for a period of 6-14 weeks in obese subjects found a small but significant effect of the supplement in reducing body weight however, this effect was largely...

Technique of indirect calorimetry

Inspiratory and mixed expiratory gases must be sampled. O2 concentration may be measured by a fuel cell sensor or a fast response, paramagnetic sensor. CO2 is usually measured by infrared absorption. Sensors may be calibrated with reference to known concentrations of standard gas or by burning a pure fuel with a predictable O2 consumption. Measurements are usually made at ambient temperature, pressure and humidity prior to conversion to standard temperature, pressure and humidity. In order to calculate metabolic rate (energy expenditure) inspired and expired minute volumes are required. It is common for one minute volume to be measured and the other derived from a Haldane transformation

Cytochrome P450 Identification

Unequivocal identification of one or more specific cytochrome P450 enzymes responsible for the metabolism of new therapeutic agents is the cornerstone of in vitro metabolism studies. This information is also critical for the follow-up cytochrome P450 inhibition and induction studies in the overall evaluation of in vitro drug-drug interactions. For all these studies, the experimental conditions should be that the measured initial reaction rates (in terms of product formation) are linear with respect to enzyme concentration and incubation time. It is preferable to use low enzyme concentration (e.g., below 0.5mg human liver microsomal protein per mL) and short incubation time (less than 20 min) to minimize protein binding and depletion of substrate and inhibitor (no more than 20 consumption, preferably less than 10 ). If the analytical sensitivity is not an issue, lower enzyme concentration and shorter incubation time are highly desirable. In case of a slow substrate turnover, higher...

Pathology and pathogenesis

Associated with delirium are functional rather than anatomical. There have been studies of patients with delirium resulting from localised anatomical lesions of the brain. These have highlighted certain areas as having an important role in producing the symptoms of delirium. These include the right cerebral hemisphere (particularly the parietal cortex)39 and subcortical structures (particularly the thalamus).40 The frontal lobes are also suspected to be involved as they are known to subserve functions of major importance in delirium, such as attention.41 Much of the functional research of delirium has been obtained from EEG studies. An important conclusion from the early research by Engel and Romano was that delirium was probably due to a global reduction in brain metabolic rate. This was proposed from the finding that delirium produced slowing of EEG activity.42

Cytochrome P450 Induction

To determine if an NME is a cytochrome P450 inducer, the compound, at several concentrations, is incubated with primary human hepatocytes for two to five days, and the metabolic rates for probe substrates of individual cytochrome P450 (generally CYP1A2, 2C9, 2C19, and 3A) are measured 32, 33 . The NME concentrations should be relevant to its therapeutic range or, if the theoretical range is not known, a pilot study covering two to three orders of magnitude may be appropriate. The enzyme activity is

Endocrine glands and hormones

Fig. 5.1 The location of endocrine glands involved in energy metabolism. Fig. 5.1 The location of endocrine glands involved in energy metabolism. major hormone-producing glands, and some exocrine tissues, relevant to energy metabolism will be considered. The location of the glands to be discussed is shown in Fig. 5.1.

Triggers of Axonal Injury in Patients with MS

Although, as described previously, there is some correlation between the numbers of CD8+ T-cells and acute axonal injury in MS lesions, this correlation is very weak in comparison to that with activated macrophages and microglia cells. The close association between degenerating axons and macrophages was noted nearly 100 years ago in a study by Fraenkel and Jakob (1913) and has recently been confirmed in more detailed quantitative studies (Ferguson et al., 1997 Trapp et al., 1998 Kornek et al., 2000). Several different toxic products of macrophages have been identified, which may mediate axonal injury in vitro or in vivo in experimental models. Proteases, directly applied into the CNS parenchyma, may not only trigger demyelination, but also axonal injury (Anthony et al., 1998). Other molecules that are likely to be involved in axonal injury are reactive oxygen or nitrogen species (see Chapter 18). Nitric oxide, applied on demyelinated nerve fibers in vitro, can induce acute conduction...

Question And Answer Session

If creatine is truly a major osmolyte and fluctuates with this huge 15-20 percent decrease with hypoosmolality, how do we explain the maintenance of energy metabolism because creatine and phosphocreatine are one and the same thing in your hands And in Dr. Baslow's theory, he needs to demonstrate changes in energy metabolism. DR. VERBALIS And I think that I gave you my explanation to both of those points, which is I believe that one of the factors that has not been taken into account in understanding brain energy metabolism, or even neurotransmission, are the separate pools of these various osmolytes that are involved with distinct cellular processes.

Watersoluble b vitamins what impact do they have on wound healing

Although the role of nutrition in the various phases of wound healing is well recognized, the action of each of the B vitamins in this regard is still being defined. It is clear that the B vitamins have specific metabolic functions, and that they interact with one another in order to ensure that wound-related energy metabolism and tissue synthesis occur appropriately. Studies have shown that B vitamins play initial coen-zymatic roles during the inflammatory phase and during the removal of dead tissue and bacteria. B vitamins also have critical roles in the proliferative and remodeling phases of wound healing in that they participate in the synthesis and interlinking of collagen and, therefore, the synthesis of new tissues and blood vessels. During the third or final phase of wound healing, myofibroblasts are dependent on B vitamins when they pull the edges of wounds inward and continue to strengthen the scar for up to 2 yrs.2 During all phases of wound healing, substantial amounts of...

The Hypothalamus PituitaryAdrenal Axis

Glucocorticoids have many peripheral effects that principally involve modulation of energy metabolism and of the immune system. These hormones also readily reach the brain, where they exercise a negative feedback on their own secretion and where they regulate many behavioral and neurobiological activities (for review, see ref. 5). These effects are mediated by binding of glucocorticoids to two receptors the mineralocorti-

Effects of bglucans on energy and carbohydrate metabolism

The antidiabetic effects of P-glucans have been suspected in response to their actions on energy and glucose metabolism. Longer studies have been designed to observe the beneficial metabolic effects of P-glucans on type 2 diabetes. The risk of developing type 2 diabetes has been shown to be more than twice as high when consuming a diet high in glycaemic load in combination with a low fibre intake.70'72 Another study has shown that the addition of P-glucan greatly reduced hyperglycaemia but that there was a threshold level for the amount of fibre.64 In diabetics, P-glucans-enriched diets have also been shown to improve metabolic control with a decrease in haemoglobin A1c (HbA1c).7374 However, only a few studies have focused on the

Comprehensive Functional Model For

In neurons, and the steady-state levels maintained there, would reflect the metabolic state of neuronal mitochondria because of the direct coupling of NAA production to a-ketoglutarate formation from glutamate. By preferentially using the aspartate aminotransferase reaction instead of the glutamate dehydrogenase reaction to generate a-ketoglutarate, neuronal mitochondria would prevent ammonia production associated with the glutamate dehydrogenase reaction, and this might avoid additional metabolic stress on neurons. In this model, NAA synthesis is intimately associated with the proper functioning of neuronal energy metabolism via the aspartate aminotransferase reaction in neuronal mitochondria. Further, NAA synthesized in neuronal mitochondria is transferred to oligodendrocytes by an as yet unknown mechanism, where ASPA liberates the acetate moiety to be used for myelin lipid synthesis. This hypothesis emphasizes the metabolic

Cerebral Microvascular Blood Flow Changes during Functional Activation

During increased neuronal activity, vasodilation occurs in the active brain areas. The concept of neurovascular coupling has already been postulated in the 19th century by Roy and Sherrington (for reference see 3 ). From their observations Roy and Sherrington postulated that unknown signals during increased activity of neurons in the brain induce regional vasodilation and increase of blood flow. Despite extensive research these signals are still not fully understood. In addition, relevant aspects of the different temporal and spatial kinetics of cellular energy metabolism and oxygen consumption leading to the observed complex changes in regional cerebral blood oxygenation have remained enigmatic. Nevertheless, the vascular changes based on the phenomenon of neurometabolic and neurovas-cular coupling are widely utilized under experimental and clinical conditions by modern techniques providing non-invasive functional brain imaging, where they serve as surrogate markers for neural...

Effects Of Nondigestible Carbohydrates

Hepatic lipogenesis was decreased by inulin80 and the decrease probably participated in the reduction of plasma TG concentrations. Unlike liver lipogenesis, neither cholesterol synthesis nor concentrations of mRNA for lipogenic enzymes in adipose tissue were modified by inulin. More conflicting results were reported in type II diabetic patients and in subjects with moderate hyperlipidemias. NDCs decreased plasma cholesterol but had no effect on plasma TG85-87 or plasma lipids.88 89 These discrepancies suggest that the metabolic effects of NDCs on lipid

Pathophysiological consequences of hyperthyroidism

Thyroid hormone exerts its effects directly via specific nuclear receptors and through central activation of the sympathoadrenal system. The increased basal metabolic rate, often exacerbated by pyrexia due to impaired thermoregulation, is associated with an increase in oxygen consumption and carbon dioxide production and a hyperdynamic circulation. Consequently, patients are at risk of developing arrhythmias and myocardial ischemia, while respiratory muscle weakness may lead to ventilatory failure.

Cerebral Microvascular Blood Oxygenation Changes during Increased Inhibition or Cortical Deactivation

As previously described, noninvasive functional imaging of the activated brain relies on the elevation of glucose and oxygen metabolism, blood flow, and oxygenation due to increased neuronal activity, leading to, for example, an increase of the blood oxygenation level-dependent (BOLD) MRI signal. Traditionally, functional activation is equated with increased excitatory synaptic activity, accompanied by an increase in energy metabolism and CBF and blood hyper-oxygenation. On the other hand, reduced activity can be caused either by a decrease in excitatory input to the region of interest (deactivation) or by active synaptic inhibition within the region of interest. Active inhibition is based on the excitation of g-aminobutyric acid (GABA)-releasing interneurons followed by the interaction of GABA, the main inhibitory neurotransmitter in the brain, with its target receptors. Whereas deactivation is accompanied by a decrease in energy metabolism and glucose consumption within the...

Health Impact of Obesity

Obesity can negatively impact a young person's health in many ways besides the neurological, cardiovascular, and metabolic effects. The patient is at risk for developing hepatic steatosis, polycystic ovary disease, and orthopedic problems like slipped capital femoral epiphysis, pseudotumor cerebri, and sleep apnea 45 . Finally, the psychosocial trauma of low self-esteem and social isolation can significantly impact the quality of the child's life. Having a chronic disease like obesity, with or without comorbidities, can be traumatic for a pre-adolescent or an adolescent. In one cross-sectional study by Schwimmer et al., 106 severely obese children and adolescents aged 5 to 18 years ranked their health-related quality of life the same as did children and adolescents with cancer 46 .

Effect of nondigestible oligosaccharides on glucose and lipid metabolism a phenomenon linked to a decrease in food

In most studies showing the interesting effects of NDOs on lipid or glucose metabolism, and fat mass development, the animals supplemented with NDOs exhibited a lower energy intake, suggesting that NDOs have a satietogenic effect. How does this take place Is it really one of the important metabolic effects of NDOs The second part of the chapter will be devoted to these questions.

Physiological changes during sleep

Although respiratory rate tends to increase during NREM sleep (and becomes irregular during REM sleep), minute ventilation falls by 0.5 to 1.5 l min mainly as a result of a decrease in tidal volume. This decrease is most pronounced during REM sleep. The resultant alveolar hypoventilation produces a mean fall of 3 to 10 mmHg (0.4-1.3 kPa) in PaO2 and an increase of 2 to 8 mmHg (0.2-1.1 kPa) in PaCO2. Owing to the shape of the oxyhemoglobin dissociation curve, oxygen saturation is well maintained if the individual has a normal awake PaO2. The most important factor contributing to the decrease in minute ventilation appears to be the decrease in resting tone of the upper airway musculature, which leads to increased airway resistance and, particularly in the supine position, predisposes to intermittent upper airway obstruction. In addition, intercostal muscle tone is progressively lost as sleep deepens and virtually disappears in REM sleep. During these stages, minute ventilation is...

Neurological Disorders and Neurodegenerative Diseases

The norepinephrinergic system seems to be indirectly involved in depression. The compound reserpine can provoke depression and a variety of antidepressive agents prolong the half-life of catecholamines, either by inhibition of their re-uptake or by decreasing the metabolic rate (for example, by inhibiting monoamine oxidase MAO). Modifications to the density of epinephrinergic receptors and phasic variability in the level of norepinephrinergic metabolites have been found in patients suffering from depression. In particular, postsynaptic a2 receptor down-regulation seems to be prevalent in depression, combined with increased presynaptic receptor sensitivity and increased a2 receptor density in the LC. Decreased norepinephrinergic receptor sensitivity and increased norepinephrinergic turnover have been noted in patients with anxiety, generalized anxiety disorder and posttraumatic stress disorder.

The role of glucagonlike peptide1 in the improvement of food intake fat development and diabetic state by nondigestible

The issue of peripheral versus intraportal GLP-1 delivery is likely to be important since previous studies have demonstrated that GLP-1R- - mice or wild-type mice with Ex-9 infused into the portal vein have impaired hepato-portal glucose sensor function and reduced insulin secretory capacity (Burcelin et al. 2001). We propose that the production of GLP-1 in the proximal colon of OFS-fed mice is a key event explaining the metabolic effect of this NDO, since the decrease in food intake, in fat mass and in glycemia classically observed after OFS treatment is abolished in GLP-1R- - mice or in EX-9-infused mice (Cani et al. 2006a). In addition to the therapeutic effect of GLP-1 through its direct pancreatic effect on insulin or glucagon secretion, the anti-hyperglycaemic effect of OFS could also be attributed to the extra-pancreatic indirect actions of GLP-1 on hepatoportal neural mechanisms. Other authors have recently debated the GLP-1 levels that need to be reached to achieve metabolic...

Iron Sulfur Proteins in Organisms Harboring Hydrogenosomes and Mitosomes

The common feature of organisms with hydrogenosomes or mitosomes is that they inhabit oxygen-poor environments. Their energy metabolism is fermentative, producing pyruvate via a classic Embden-Mayerhof pathway however, the further metabolism of pyruvate, a key intermediate product, which is linked to ATP production by substrate-level phosphorylation only, is significantly different. Consequently, a different set of FeS proteins is involved in this process. These proteins are compartmentalized either into hydrogenosemes (Trichomonas, Neocalimastix) or into the cytosol (Entamoeba, Giardia, Cryptosporidium, microsporidia) (Hackstein et al. 1999 Katinka et al. 2001 M ller 1988, 2003 Xu et al. 2004 Table 6.1). 2Fe2S ferredoxin is a principal electron carrier in trichomonad hydrogeno-somes that is required for both pyruvate-as well as malate-dependent catab-olism. The hydrogenosomal ferredoxin is of mitochondrial (adrenodoxin) type, displaying low redox potential (Yarlett et al. 1986b). In...

Relevance of resistant starch to weight management

RS appears to play two roles with respect to weight management. Firstly there is a reduction in the digestible energy available from the RS compared with a readily digestible starch. The presence of RS in foods reduces their caloric density. Recently, research has demonstrated a second role for RS in energy metabolism and metabolic control. The lower glucose and insulin impact of RS causes changes in lipid metabolism that favor lower levels of lipid production and storage. In addition, RS is fermented within the large bowel by the indigenous colonic bacteria producing an important range of compounds called short-chain fatty acids (SCFAs). The amount and type of SCFA produced are proposed to affect carbohydrate and lipid metabolism in the body, particularly in the liver, muscle and adipose tissue. The known effects of RS in relation to weight management are listed in Table 8.1. Each of these aspects will be discussed later in this chapter.

Pathophysiology of sickling

Sickle cell disease presents a wide spectrum of pathology. Hemolytic aspects include the problems of rapid red cell destruction, anemia, jaundice, pigment gallstones and those associated with the compensatory bone marrow response such as aplastic crisis, increased requirements of folic acid, and an increased metabolic rate. The consequences of vaso-occlusion are generally more serious and depend upon the vessels affected, but may include stroke, retinal problems, splenic abnormalities, including acute and chronic sequestration and the loss of normal splenic function rendering patients prone to overwhelming septicemia, pulmonary problems including infection, infarction, and pulmonary sequestration, and damage to the bone marrow resulting in the painful crisis, localized avascular necrosis of bones, and involvement of the femoral head.

Summary metabolic control in a physiological setting

The terms 'somewhat' and 'slightly' were used fairly liberally in the last section. This is deliberate. The hormonal regulation of metabolism is not 'on or off' it is mostly achieved by subtle, gradual changes. An analogy was used earlier to describe control of the plasma glucose concentration by insulin, likening the glucose concentration to the temperature in a water bath which triggers a thermostat to switch a heater (the insulin concentration) on or off. By now it should be clear that a much better analogy is that of a proportional control system. The thermostat is not of the 'either on or off' kind. It regulates the flow of current through the heater depending on the departure of the water temperature from the desired temperature - the 'set-point'. The more the temperature falls below the set-point, the greater the current through the heater. As the temperature rises to the set point, the current diminishes to just that required to balance heat loss. If the temperature rises...

Starch digestion and absorption

Most of the starch present in the diet is cooked and gelatinized. As such, most dietary starch is easily digested, accounting for approximately 95 of that consumed (Cassidy et al., 1994). Various diet, food processing and physiological factors are known to affect starch digestion, and these are listed in Table 8.3. Starch is digested hydrolyzed enzymically and sequentially within the upper gastrointestinal tract (Gray, 1992, 2003 Levin, 1994). In the mouth some starch is digested to maltose via salivary amylase. In the small intestine, starch is initially digested in the lumen via pancreatic amylase to smaller compounds that include maltose, maltotriose and branched limit dextrins. Two more enzymes produced by the brush border (sucrase-isomaltase and glucoamylase) further hydrolyze the starch products to glucose which is actively absorbed through the enterocyte membrane. Most dietary starch is absorbed as glucose to participate in energy metabolism in the body.

Systemic Disease Affecting Waldeyers Ring

Tangier's disease (familial hypo-alpha-lipoproteinemia) is an autosomal-recessive metabolic disease with a deficiency of high-density lipoproteins and extremely low levels of plasma cholesterol 85 . The deranged fat metabolism results in storage of cholesterol esters in the reticuloendothelial system and macrophages of the pha-ryngeal and gastrointestinal tract mucosa, but also in smooth muscle cells, pericytes and Schwann cells of pe

Iron as a Recent Evolutionary Pressure on Reproductive Fecundity

Iron may play another important role in achieving a normal term pregnancy. Hypoxia inducible factor 1a (HIF-1a) is a component of the master transcription regulator (HIF) for genes that respond to hypoxia or iron deficiency. In the presence of oxygen and iron, proline residues in two degradation domains are altered by HIF-1-prolyl hydroxylases leading to ubiquitination and degradation of HIF-1a. HIF-1a is thus stable in conditions lacking oxygen or iron (49). Pre-eclampsia (pregnancy induced hypertension) is the leading cause of fetal and maternal mortality worldwide. Vascular endothelial growth factor (VEGF) may be compromised in pre-eclamptic mothers. The pre-eclamptic placenta produces elevated levels of a soluble tyrosine kinase 1 receptor that catches free VEGF. This capture of VEGF compromises the vasculature of the kidney, brain lungs and other organs which are deprived of essential survival and maintenance signals, and hence dysfunction. This has been shown to lead on to...

HSF1 as a Developmental Regulator

Albeit HSF 1 plays its most prominent role in protecting cells and organisms from proteotoxic stresses, several lines of genetic evidence support a versatile role for HSF1 in regulation of development. In yeast, HSF is essential for viability also under normal growth conditions, and more recendy, a genome-wide analysis of S. cerevisiae HSF targets showed that HSF participates in diverse biological pathways, such as energy metabolism, synthesis of cytoskeletal components and vesicular transport.3 ,68 In higher invertebrates and vertebrates, HSF HSF1 is not required for survival, but its absence causes severe reproductive disturbances, a reduction in body size and deficient embryonic development. For example, the deletion of the v gene leads to defect oogenesis and larvae development in Drosophila. hsfl knockout mice undergo normal oogenesis but have malformed chorioallantoic placenta, resulting in high prenatal lethality. Moreover, hsfl'1' females are infertile, which is due to HSF1...

Why an [FeOnly Hydrogenase

The use of fumarate as an endogenous electron acceptor requires a well-controlled balance between the various catabolic and anabolic reactions in the cell. Depending on the metabolic state of the cell, the NADH pool might be subject to large fluctuations. The presence of alternative oxidases in anaerobic mitochondria demonstrates how the cell can cope with such fluctuations in the NADH pool (Tielens and van Hellemond, Chap. 6 in this volume). Such an alternative oxidase appears to be absent in N. ovalis, and the hydrogenase could fulfil the task of regulating the NADH pool. More detailed knowledge of the hydrogenosomal metabolism of N. ovalis, however, is required to judge the various metabolic roles of the hydrogenosome. The current data (Boxma et al. 2005) support a role in amino acid and lipid metabolism - besides its role in energy metabolism. Therefore, changes in the NADH pool in the response to varying metabolic activities are likely that would require a homeostatic adjustment.

Mribased Control Of Energy Delivery

The role of MRI during thermal ablations is to monitor temperature levels, to restrict the thermal coagulation to the targeted tissue volume, and to avoid heating of normal tissue. MRI can also detect irreversible tissue necrosis and demonstrate permanent changes within the treated tissue. Physiologic effects such as perfusion or metabolic response to elevated temperature can also be used for monitoring the ablation. Both flow and tissue perfusion can affect the rate and extent of energy delivery and the size of the treated tissue volumes (3). Monitoring can optimize treatment protocols.

Metabolic Imaging And Intelligence

Chase et al. (1984) used PET to investigate the resting metabolic rate of a sample of Alzheimer's Disease patients and a small selection of normal control subjects. They reported moderately strong positive correlations between the full score, verbal and performance IQ on the WAIS-R and cortical glucose metabolic

Perturbations in thermodynamics in the critical care setting

Although the primary cause of fever is resetting of the thermoregulatory set-point, both heat production and heat loss are likely to be perturbed in the critical care setting. Heat production is equal to the metabolic rate or total energy expenditure. The inflammatory response tends to increase energy expenditure, and this effect appears to be particularly marked with burn injuries. Fever itself results in increased energy expenditure by increasing the rate of metabolic reactions. Despite these factors, most intensive care unit (ICU) patients are not hypermetabolic in terms of total energy expenditure when compared with normally active individuals. Abolishing activity reduces energy expenditure by up to 50 per cent, and sedation and paralysis with mechanical ventilation reduce energy expenditure by at least a further 20 per cent (M a.n.t.h.o u.s . L L 1995).

Traumatic Brain Injury

Reduced NAA concentrations can reflect neuronal death, but this mechanism cannot account for the reversible decreases in NAA observed in multiple sclerosis 22 and stroke 23 , or the possible increases over time, post-injury, observed in our TBI sample 18 . Given Gasparovic's results, and the fact that our NAA analyses were undertaken in normal appearing tissue, it may well be the case that individual variation in metabolism, rather than loss of neurons, underlies the well-established relationship between NAA and concurrent and long term cognitive function. Consistent with this possibility, Positron Emission Tomography analysis has shown that NAA concentrations correlate with overall metabolic rate 24 , which is often reduced after TBI.

Recent PET findings in neurodegenerative disorders

Relatively localized abnormalities of regional cerebral glucose metabolism have been recognized for some time in Alzheimer's disease, and the distribution of such changes appears to be different from that associated with Lewy Body Dementia. A method to detect extracellular b-amyloid deposits (which constitute senile plaques) in vivo recently became available. By modifying thioflavin-T, an amyloid-binding dye, a collaborative research group obtained a suitable PET ligand, N-methyl- 11C 2-(40 or ''Pittsburgh Com-pound-B'' (PIB). In a preliminary study, 25 AD patients (mild to moderate disease) underwent dual PIB and FDG PET and were compared to controls. PET identified a significant accumulation of PIB in the frontal and tem-poroparietal cortices, compatible with postmortem studies of amyloid deposition. There was no significant correlation between PIB uptake and cognitive impairment, but this may reflect the preponderance of individuals with early and intermediate disease....

Mitochondrial Dysfunction

Several lines of evidence suggest that mitochondrial function is indeed impaired in MS and EAE, in line with expectations based on the previous observations, although whether NO is responsible for the impairment is not yet clear. However, oxidative damage to mitochondrial DNA has been reported in active MS plaques (Vladimirova et al., 1998 Lu et al., 2000) associated with an impaired NADH dehydrogenase activity (Lu et al., 2000). A pronounced reduction in the axonal density of ATPase-positive mitochondria has been described in a subset of acutely demyelinating plaques (reported in Smith and Lassmann, 2002). Microarray analysis of MS normal-appearing white matter has also revealed the upregulation of genes that reflect a higher energy metabolism (Graumann et al., 2003). The cause for this upregulation is not yet clear, but it is arguably in compensation for a diminished energy production from the existing mitochondria. The same study reported evidence suggesting a global defense...

Changes in respiratory function

Oxygen consumption is increased by about 20 per cent and the maternal metabolic rate by 15 per cent. This increase in demand is met by a 40 to 50 per cent increase in resting minute ventilation, resulting mainly from an increase in tidal volume rather than from an increased respiratory rate. This change in ventilation may be due to the respiratory stimulant effect of progesterone. Later in pregnancy, the elevation of the diaphragm caused by the enlarging uterus leads to a decrease in functional residual capacity, but diaphragm excursion is unaffected and so vital capacity is unchanged. A reduced functional residual capacity means that tidal ventilation occurs at lower lung volumes and may encroach on the closing volume. This may lead to pulmonary shunting in conditions where the closing volume is increased (e.g. obesity and the supine position).

Mechanism of Action

The mechanism of action of thiazolidinediones has not been fully elucidated however, the unique effects of this class of oral medications on glycemia as well as multiple vascular risk factors appear to be based on their amelioration of some of the patho-genetic links between visceral adiposity, insulin resistance, and type 2 diabetes (Fig. 1). The binding of PPARY by a thiazolidinedione is known to affect the transcription of a number of genes 2 . Animal studies have offered some insight into the effects of thiazolidinediones on glucose and fat metabolism. Free fatty acids (FFA) are believed to be a major contributor to insulin resistance by inhibiting insulin action in skeletal muscle and the liver 3 . One of the main actions of the thiazolidinediones is to lower circulating levels of FFA by increasing their retention in certain adipose tissue depots 4 . Thiazolidinediones are potent inducers of the differentiation and proliferation of precursor cells into small, metabolically active...

Recovery Following Injury to the Spinal Cord

Response, with migration of inflammatory cells and cytokines. In addition, there are biochemical changes, with impaired energy metabolism, excitotoxic mechanisms, arachidonic acid release, free radical production, lipid peroxidation, electrolyte shifts, increased intracellular Ca, increased intracellular K and increased intracellular Na 31 .

Fdgpet In Metastatic Breast Cancer

Assessment of therapeutic response can also be studied by means of FDG-PET. A relative decrease of the standardised (FDG) uptake value of 20 compared to baseline, is considered to indicate a response (5). In one study in a neo-adjuvant setting, uptake of FDG was significantly decreased after one course of chemotherapy compared to baseline, in responding breast cancer patients (n 51 patients) (24). Metabolic response determined with FDG-PET was more predictive of histopathological response than clinical examination or ultrasound imaging. Similar results were previously shown by Smith et al., in 30 patients with primary and metastatic breast cancer (25). However, in a recent report, histopathological tumour response could not be predicted in patients with low initial FDG uptake (in a large part of the patients 57 out of 96) (26). Thus far, no studies have been performed in which treatment differentiation in breast cancer was based on tumour response assessment by means of FDG-PET....

Ca Homeostasis in Excitable Cells

Calcium is a key ion that contributes to excitation and links cellular activity to metabolism. This ion affects a wide variety of neuronal functions including synaptic transmission and plasticity, axoplasmic transport, gene expression, growth, apoptosis, and energy metabolism (Bootman et al., 2001 a, 2001b Spira et al., 2001 West et al., 2001). Therefore its concentration and spatiotemporal distribution in excitable cells are tightly controlled (Bootman et al., 2001a Petersen, 2002). Cells possess a number of powerful homeostatic systems charged with maintaining control over Ca concentrations in the cytosol (Carafoli, 2002). The components include plasmalemmal Ca extrusion systems (Ca-ATPase, Na-Ca and Na-K-Ca exchangers) (Blaustein and Lederer, 1999 Lytton et al., 2002 Shull et al., 2003), cytosolic Ca-binding proteins (parvalbumin, calbindin-D28K, calmodulin and others) (Heizmann and Hunziker, 1991 Schwaller et al., 2002), mitochondrial Ca uptake and release, and the SR ER Ca-ATPase...

Neuroanatomical Studies

Deficits in impulse control and executive functions have been robustly linked to frontal lobe abnormalities. As above, the gambling task, a measure of impulsive decision making, is significantly impaired in patients with orbito-frontal lesions (Bechara et al, 1994). Impulsive patients, such as borderline personality disorder patients, have decreased frontal glucose metabolic rates, and those with greater aggression have lower frontal activity (Goyer et al, 1991). Further, electrophys-iological studies demonstrate a link between impulsivity and impaired frontal function (Kiehl, Hare et al, 1999 Barratt, Stanford et al. 1997).

Joseph G Rajendran MDab Kenneth A Krohn PhDab

Ischemia and hypoxia are not synonymous the former is a lack of perfusion and can lead to hypoxia, although it may not be evident until the late stages of ischemia. Tissue hypoxia can also be present in the absence of significant ischemia. Many solid tumors develop areas of hypoxia during their evolution. This is primarily caused by unregulated cellular growth, resulting in a greater demand on oxygen for energy metabolism. High interstitial pressure may exacerbate the already inefficient vascularization within the tumor 10 . In addition, other factors, such as low O2 solubility (anemia), might increase levels of tissue hypoxia. Clinicians owe an understanding of the mechanistic aspects of hypoxia as a variable in response to cancer therapy to Thomlinson and Gray 11 , who in the last century showed the impact of a distance greater than 200 mm from a capillary on cell viability and survival (Fig. 1).

Signaling Pathways That Control Gene Activity

Even mature cells that are part of a differentiated tissue constantly change their patterns of gene expression. In large measure this occurs because of many different cell-surface receptors that continually receive information from extracellular signals and transduce this information into activation of specific transcription factors that stimulate or repress expression of specific target genes. Many such signaling pathways lead to alterations in the cell's metabolic activities. Liver, for example, responds to fluctuations in the levels of many hormones (e.g., insulin, glucagon, and epinephrine) by altering expression of many genes encoding enzymes of glucose and fat metabolism. Other signaling pathways influence the levels of proteins that affect the ability of cells to progress through the cell cycle and divide.

Table 2 Differential diagnosis of thyrotoxicosis

Graves' disease may appear at any age but occurs most often in females aged 2050 years. The presenting signs and symptoms are secondary to an increased metabolic rate, increased adrenergic activity and manifestations of infiltrative dermopathy and ophthalmopathy. Patients may present with complaints of heat intolerance, weight loss in spite of an increased appetite, loose stools, tachycardia, tremor, emotional lability, fatigue and insomnia. Children may present with hyperactivity. In contrast, elderly patients may appear depressed and apathetic, having withdrawn from customary activities.

Data Acquisition Image Reconstruction And Evaluation

Compartment modeling can be helpful in the differential diagnosis of malignant tumors, as shown by Dimitrakopoulou-Strauss et al. (12,13). The authors used dynamic PET studies in patients with soft-tissue sarcomas and evaluated the impact on diagnosis as well as the correlation to grading (13). Some overlap existed when SUVs were used to differentiate benign and malignant lesions. Furthermore, SUV was helpful to identify grade III tumors, but the use of full kinetic information permitted the differentiation of further classes. The authors concluded that the evaluation of full FDG kinetics is necessary in these tumors and is superior to a single static data acquisition (13). Similar results were reported by Nieweg et al. (14), who showed a correlation of the metabolic rate and the tumor grade in soft-tissue sarcomas. Sugawara et al. (15) used FDG kinetic modeling in 21 patients with untreated and treated germ cell tumors. The major aim of the study was the evaluation of kinetic...

Variations In Glycaemic Index

Perhaps the best example of the ability of differences in glycaemic index of CHO-enriched diets to modify glycaemic control and lipoprotein metabolism in patients with Type 2 diabetes is the report by Jarvi and colleagues (38). These investigators compared the metabolic effects of two diets, each containing 55 of total calories as CHO, in 20 patients, consuming each of the test diets for 24 days. The glycaemic indices were calculated to vary from 57 to 83 as compared to white wheat bread. The two test diets were compared to each other, as well as to baseline values obtained on an uncontrolled diet. Of considerable interest was the observation that fasting plasma glucose, TG, and LDL cholesterol concentrations fell on both diets, supporting the general belief that essentially any prescribed diet is better than no diet plan. On the other hand, the degree of improvement in all of these variables was the same, irrespective of the difference in glycaemic index of the diet. Furthermore, the...

Variations In Fibre Content

When put into the context of results of earlier studies evaluating variations in fibre content, it appears that the clinical benefit is closely related to the increment in daily fibre intake. More specifically, increases in fibre intake of * 15 g day did not lead to any significant metabolic changes (44,45), whereas dietary increases up to 23 g day (46) and 30 g day (47) resulted in a modest improvement in glycaemic control, without any decrease in plasma TG concentration. Thus, there appears to be no study in which the untoward metabolic effects of CHO-enriched diets have been shown to be attenuated to the degree seen when MUFA PUFA fat is used to replace SF (20), and the only instance in which the effects were even comparable involved the daily intake of 50 g fibre (43).

Summary And Suggestions

Given the above considerations, the only unresolved question that remains in dietary recommendations for patients with Type 2 diabetes is what to substitute for SF. It is difficult to find any scientific justification for continuing to recommend the continued use of low SF-high CHO diets in patients with Type 2 diabetes. As discussed in this chapter, several alternative approaches are possible. Based on published data, it is suggested that replacing SF with MUFA PUFA is the simplest and most effective way to maximally improve glycaemic control, and attenuate the lipoprotein abnormalities characteristic of patients with Type 2 diabetes. In this context a diet containing (as per cent of total calories) approximately 15 protein, 45 CHO and 40 fat, with SF intake < 10 of total calories, does not require a substantial change in eating habits, while effectively minimising abnormalities of CHO and lipid metabolism. However, there are alternative approaches that have as their goal the...

Anatomical and Functional Imaging 1221 Fdgpet and CT

As discussed in Chapter 3, the advantages of proton MRS include being more easily available on standard MRI equipment, plus the better spatial resolution and sensitivity. In particular, MRS could be helpful for Phase I studies of new therapies against aggressive lymphomas, that target biological end points, but are not expected to dramatically alter tumor size. The observation of different trends in responders and non-re sponders suggests that further development of this method may provide a sensitive early indicator of metabolic response to treatment (p. 965) 24 . 24 A.J. Schwarz, N.R. Maisey, D.J. Collins, D. Cunningham, R. Huddart, M.O. Leach, Early in vivo detection of metabolic response a pilots study of 1H MR spectroscopy in extracranial lymphoma and germ cell tumors, Br. J. Radiol. 75, 959-966 (2002).

Strategies For Future Studies

We are investigating the potential of small molecule inhibitors that can cause downstream metabolic effects that will change tumor uptake of and the susceptibility of tumor cells to, RIT. Agents, such as tirapazamine, which affect the hypoxic fraction of tumors may also enhance RIT efficacy. Agents that cause changes in the permeability and vascularity of tumors will permit radioimmuno-conjugate access to tumor regions that may otherwise not be reached. The use of antiangiogenic agents, in particular, is of great interest as it appears clear that these agents may decrease the tumor uptake of radioimmunoconjugate (if RIT is instituted after antiangiogenic therapy), and conversely decrease egress of radioimmunoconjugate if the antiangiogenic agent is administered at an as yet undetermined time after RIT. These exciting studies are currently being designed in preclinical models and will soon be applied in the clinic.

Introduction role of dietary and supplementary calcium in weight control

In the following sections the question will be addressed as to whether a role for calcium in weight control is substantiated by facts gained from epidemiological studies and the results of in vitro, animal and human intervention studies, showing either a positive role for calcium in lipid metabolism and weight control, or no effect at all. In order to understand these effects, the role of calcium in the regulation of energy metabolism is to be examined. This comprises effects on cellular energy metabolism (the Zemel hypothesis) and the reduction of energy intake by the formation of poorly absorbable calcium soaps and a potential calcium effect on appetite.

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