Cq Cq

Cyclic 3',5'-adenosine Adenosine monophosphate monophosphate (AMP)

Fig. 2.3.1 Synthesis and breakdown of cAMP.

Cyclic GMP (cGMP): cGMP is analogous to cAMP. It is formed by guanylyl cyclase from GTP: its roles include regulation of ion transport in the kidney and relaxation of smooth muscle.

Calcium ions (Ca2+): These regulate many enzymatic processes including aspects of glycogen metabolism, skeletal muscle contraction and secretion of hormones including insulin. There are large cellular stores of Ca2+ within the endoplasmic reticulum (or the sarcoplasmic reticulum in muscle). Ca2+ can be liberated into the cytosol from these stores very rapidly in response to opening of specific ion channels. After the stimulus is removed, Ca2+ are pumped back into the stores. Many responses to elevation of cytosolic Ca2+ are mediated by their binding to a 17 kDa protein called calmodulin. Calmodulin has four high-affinity Ca2+-binding sites. It is related to the protein troponin that triggers skeletal muscle contraction (see Box 8.3).

Phosphatidylinositol and related compounds: Phosphatidylinositol is a phospholipid that is associated with the inner leaflet of the cell membrane. The hydroxyl groups of the inositol ring may be phosphorylated. One particular form, phosphatidylinositol (4',5')-bisphosphate (PIP2), is the starting point for a number of important events. It may be cleaved by phospholipase C (see below) to release inositol (1 ',4',5')-trisphosphate (IP3) and diacylgylcerol (Fig. 2.3.2). IP3 is water-soluble and diffuses to the endoplasmic reticulum where it interacts with specific receptors to release Ca2+ into the cytoplasm. Diacylglycerol, which remains associated with the membrane, acts in concert with Ca2+ to activate protein kinase C (see below). Alternatively, the enzyme phosphatidylinositol-3-kinase (see below) may phosphorylate the 3'-position on the inositol ring of PIP2, forming phosphatidylinositol (3',4',5')-trisphos-phate (PIP3). Note that PIP3 is still a phospholipid, unlike IP3 with which it should not be confused! PIP3 plays a key role in insulin signalling (see Box 2.4).

Ptdlns(4',5')-bisphosphate Ptdins(3',4',5')-trisphosphate (PIPJ

Ptdlns(4',5')-bisphosphate Ptdins(3',4',5')-trisphosphate (PIPJ

Fig. 2.3.2 PI3K, phosphatidylinositol-3-kinase; PLC, phospholipase C. ® represents a phosphate group (-PO42-).

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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