Hormones and the Control of Metabolism

Sophisticated fine-tuning of metabolic processes in multicellular organisms is possible through the actions of hormones and second messengers. 

In humans, a complex hormonal system has evolved that requires releasing factors (under the control of the hypothalamus), trophic hormones (under the control of the pituitary), and specihc hormones for target organs (under the control of endocrine glands). 

Feedback control occurs at every level of the system. 

One important system involves hormones that stimulate a membrane-bound G protein, which then stimulates adenylate cyclase to produce cAMP. In these cases, cAMP is the second messenger. 

In another important system, a hormone stimulates a different G protein that then stimulates phospholipase G. Phospholipase G converts phospha-tidylinositol 4,5-( f5phosphate (PIPg) to diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3), both of which stimulate the opening of calcium channels and the release of Ga +. In this scenario, the Ga + is the second messenger. 

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Small CJ, Bloom SR. Gut hormones and the control of appetite. Trends Endocrinol Metabol 2004 15 259-63. 

However, the control of metabolism appears to be more complicated than this as it also involves the hypothalamus and pituitary gland. It seems that the male hypothalamus produces a factor, which inhibits the release of a hormone and which therefore leaves the liver in a particular male state. In the female, the hypothalamus is inactive, and therefore produces no factor, and hence the pituitary releases a feminizing factor (possibly growth hormone), which changes the liver to the female state. 

Longer lasting control of mineral metabolism is achieved by steroid hormones elaborated by the adrenal cortex and by synthetic analogues. Besides their actions on gluconeogenesis, glycogen deposition, protein metabolism and sexual characteristics, the corticosteriods influence calcium metabolism and the control of water and electrolyte equilibria, so that profound changes accompany their administration. 

Vitamin D plays an essential role as a hormone in the control of calcium and phosphorus metabolism. It is discussed in detail in Chapter 49. 

Poly(c -l,4-isoprene) belongs to the family of polyisoprenoids, which are the most structurally diverse and abundant natural products known, with more than 23,000 primary and secondary metabolites. This huge family comprises, for example, sterols which display not only structural functions (control of biological membrane fluidity) but also hormonal functions (steroid hormones). Key phyto-hormones, such as abscisic acid, gibberellins and cytokinins, are isoprenoids too. Moreover, isoprenoids are used in protein prenylation, which is a key step in the activation and the localization of metabolic enzymes in many organisms. The first common step of all isoprenoid biosynthesis pathways is the formation of isopentenyl diphosphate (IPP). ... 

Steroids are hormones that are known to modulate DNA expression and protein expression. Adrenal hormones (e.g., aldosterone and cortisol) participate in the control of metabolism and of salt and water homeostasis. The other class of steroid hormones, gonadal hormones (e.g., estradiol, progesterone, and testosterone), influence mammalian sexual development and function. Several steroids also modulate neurotransmitter action, and some athletes have misused anabolic steroids to enhance their physical strength and performance. GC/MS has been used in conjunction with El or Cl as an ionization method for steroids to determine molecular mass, elemental composition, and length of the side chain of a steroid hydrocarbon. Although these techniques are highly sensitive, they require multistep derivatization of these thermally labile compounds. FAB-MS has proven to be a useful technique to analyze underivatized urinary... 

Greenbaum, A. L., Gumaa, K. A., and McLean, P., 1971, The distribution of hepatic metabolites and the control of the pathways of carbohydrate metabolism in animals of different dietary and hormonal status. Arch. Biochem. Biophys. 143 617. 

Apart from the mechanisms of coarse and fine control discussed above there occur in plants and animals rhythms of metabolic activity and extrinsic control mechanisms involving, in both plant and animals, hormones and, in animals only, nervous system control. The role of plant hormones in the control of growth and differentiation in plants is discussed in the next chapter. The present chapter concludes with a brief description of circadian rhythms of metabolic activity in plants and of a particular example of a timing reaction. 

Both the overall rate of protein synthesis and the translation of certain specific mRNAs are controlled by agents such as hormones, growth factors, and other extracellular stimuli. As precursors for protein assembly, amino acids also regulate the translational machinery. Because protein synthesis consumes a high proportion of cellular metabolic energy, the energy status of the cell also modulates translation factors. 

Hormones have a profound effect on carbohydrate metabolism. Great interest has been aroused by reports of hormonal control of hexokinase activity by specific proteins in animal tissues.99- 100 Hexokinase action is the rate-limiting step in the uptake of D-glucose by muscle. Hexokinase is inhibited in diabetic muscle, but the inhibition can be partially reversed by insulin. A protein fraction from the anterior pituitary gland will inhibit the hexokinase of extracts of brain and muscle, and the effect of this... 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

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