The first strategy for head group attachment is illustrated by the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol in E. coli. The diacylglycerol is activated by condensation of phosphatidate with CTP to form CDP-diacylglycerol, with the elimination of pyrophosphate (Fig. 20-23). Displacement of CMP through nucleophilic attack by the hydroxyl group of serine or by the C-1 hydroxyl of glycerol-3-phosphate yields phosphatidylserine or phosphatidylglycerol-3-phosphate, respectively. The latter is processed further by cleavage of the phosphate monoester (with release of P i ) to yield phosphatidylglycerol.
The diagnosis and treatment of nonclassic CAH (NCCAH) due to 21-hydroxylase deficiency are reviewed here. The genetics and clinical manifestations of the nonclassic form of 21-hydroxylase deficiency and the classic form of 21-hydroxylase deficiency are reviewed separately. (See "Genetics and clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults" .)
The secretion of hypothalamic, pituitary, and target tissue hormones is under tight regulatory control by a series of feedback and feed- forward loops. This complexity can be demonstrated using the growth hormone (GH) regulatory system as an example. The stimulatory substance growth hormone releasing hormone (GHRH) and the inhibitory substance somatostatin (SS) both products of the hypothalamus, control pituitary GH secretion. Somatostatin is also called growth hormone-inhibiting hormone (GHIH). Under the influence of GHRH, growth hormone is released into the systemic circulation, causing the target tissue to secrete insulin-like growth factor-1, IGF-1. Growth hormone also has other more direct metabolic effects; it is both hyperglycemic and lipolytic. The principal source of systemic IGF-1 is the liver, although most other tissues secrete and contribute to systemic IGF-1. Liver IGF-1 is considered to be the principal regulator of tissue growth. In particular, the IGF-1 secreted by the liver is believed to synchronize growth throughout the body, resulting in a homeostatic balance of tissue size and mass. IGF-1 secreted by peripheral tissues is generally considered to be autocrine or paracrine in its biological action.