POMC Mutations

Although not due to defects in the prohormone-processing machinery, two human cases of POMC deficiency caused by genetic defects are of interest94 because mutations in the POMC gene also lead to early onset morbid obesity. The phenotypic attributes of one female patient were obesity (> 30kg at 3 years of age), ACTH deficiency, and red hair pigmentation. Symptoms of increased appetite had been observed since 4 months of age. Direct sequencing of PCR products containing the entire coding region...

Figure

A schematic description of the major processing steps in the maturation of pituitary pre-proopi-omelanocortin (POMC). POMC is synthesized by ribosomes, a preprohormone containing a hy-drophobic signal peptide at the N-terminus. After targeting to the endoplasmic reticulum (ER) via binding to the signal recognition particle (SRP), this preprohormone associates with the ER membrane, the signal peptide traverses the membrane, and is cleaved off cotranslationally. POMC is then transported to the...

Contents

5.1 ACS1 Structure and 5.2 ACS1 Gene Expression Tissue Distribution and Developmental 5.3 The ACS Gene 5.4 Nutritional and Hormonal Regulation of ACS1 Gene Expression 82 5.5 Disease State-Specific Regulation of ACS1 Gene Expression 87 The Acyl-CoA synthetase 1 (ACS1) (EC6.2.1.3)1 gene encodes a key gatekeeper enzyme in long-chain fatty acid metabolism. ACS1 catalyzes the activation of free long-chain (C12-18) fatty acids to long-chain acyl-CoA esters, the requisite initial step in the cellular...

PCI Mutations

The first human disorder thought to be due to impaired prohormone processing, multiple endocrinopathy, was reported in 1995 at about the same time as the fat mutation in mouse.93 The two diseases, caused by PC1 and CPE mutations, respectively, are remarkably similar in appearance. The 43-year-old-female proband was obese (89.2 kg body weight and 34.4 kg m2 body mass index (BMI) from childhood (36 kg at 3 years of age)). The proband had come to clinical attention because of infertility and...

Tissue Distribution of UCP2 Implicates a Role in Immune Function

At least at the mRNA level, the UCP2 gene is expressed in an enormous assortment of tissues and cell types. Some of these tissues, such as skeletal muscle, adipose tissue, and even certain brain regions such as hypothalamus, would be consistent with hypotheses that UCP2 has a role in energy expenditure and fuel metabolism. By contrast, the relative abundance of transcripts for UCP2 in tissues such as lung, spleen and intestine2099 immediately raised the question as to why there would be...