Metabolic pathways hormones

Proteins constitute a universally essential class of macromolecules which perform a wide range of specialized functions in living systems. Examples of these functions include the enzymatic catalysis of metabolic pathways, hormonal signaling in the endocrine system, and antibody mediated defense in the immune system. Proteins also perform critical structural roles, for example as the muscle proteins actin and myosin. The study of protein structure and function is therefore essential to our understanding of life and the advancement of medicine [1]. 

Biochemistry is carbonyl chemistiy. Almost all metabolic pathways used by living organisms involve one or more of the four fundamental carbonvl-group reactions we ve seen in Chapters 19 through 23. The digestion and metabolic breakdown of all the major classes of food molecules—fats, carbohydrates, and proteins—take place by nucleophilic addition reactions, nucleophilic acyl substitutions, a substitutions, and carbonyl condensations. Similarly, hormones and other crucial biological molecules are built up from smaller precursors by these same carbonyl-group reactions. 

Metabolic pathways are regulated by rapid mechanisms affecting the activity of existing enzymes, eg, allosteric and covalent modification (often in response to hormone action) and slow mechanisms affecting the synthesis of enzymes. 

Such observations as these should inject caution into those who speak glibly about what metabolism is like in the mammalian organism. Furthermore, if differences such as these exist among different species of higher mammals, it lends credence to the idea that, within the human species, quantitative differences of a similar nature may exist. Because of differences in enzyme systems and the extent to which different metabolic pathways are utilized in different individuals, it is not at all unreasonable to conclude that different individuals probably have fundamental needs for quite different levels of the thyroid hormone. 

The physiological pathway for oxidation of fatty acids in organs or tissues starts with the enzyme triacylglycerol lipase within adipose tissue, that is, the hormone-sensitive lipase. This enzyme, plus the other two lipases, results in complete hydrolysis of the triacylglycerol to fatty acids, which are transported to various tissues that take them up and oxidise them by P-oxidation to acetyl-CoA. This provides a further example of a metabolic pathway that spans more than one tissue (Figure 7.13) (Box 7.1). 

Hydrophilic hormones and other water-soluble signaling substances have a variety of biosynthetic pathways. Amino acid derivatives arise in special metabolic pathways (see p. 352) or through post-translational modification (see p. 374). Proteohormones, like all proteins, result from translation in the ribosome (see p. 250). Small peptide hormones and neuropeptides, most of which only consist of 3-30 amino acids, are released from precursor proteins by proteolytic degradation. 

E. Hormonal control provides a major means for regulation of metabolic pathways,... 

Two female sex hormones, estradiol-17 and progesterone, and one male sex hormone, testosterone, are used as growth promoters on beef cattle (Fig. 7.1). By nature, they are all endogenous products playing an important role in controlling reproductive functions in humans and animals. When applied exogenously they will enter the same metabolic pathways as the endogenously produced molecules. 

As well as the sex hormones already mentioned (see above), many other hormones seem to affect the metabolism of foreign compounds and therefore may have effects on toxicity. A number of pituitary hormones may directly, as well as indirectly, affect metabolism, for example, growth hormone, follicle-stimulating hormone, adrenocorticotrophic hormone, luteinizing hormone, and prolactin. Thus, hypophysectomy in male rats results in a general decrease in metabolism, but the effects of some of the individual hormones may depend on the sex of the animal and the particular enzyme or metabolic pathway. For example, adrenocorticotrophic hormone (ACTH) administration decreases oxidative metabolism in males but increases N-demethylation in female rats. Removal of the adrenal gland reduces metabolism, such as ethylmorphine demethylation and aniline 4-hydroxylation, and this can... 

The function of the target molecule may be critical or mncritical. Thus, if the target molecule is an enzyme, this could be involved in a crucial metabolic pathway, such as mitochondrial oxidative phosphorylation. In this case, an adverse interaction with the ultimate toxicant is likely to lead to cell dysfunction and possibly death (e.g., as with cyanide or salicylate). Chemicals such as methimazole and resorcinol, which are activated to free radical intermediates by thyroperoxidase, cause destruction of the enzyme. This then disturbs thyroid hormone synthesis and thyroid function with pathological consequences such as thyroid tumors. 

Chapters 20 through 22 describe the major anabolic pathways by which cells use the energy in ATP to produce carbohydrates, lipids, amino acids, and nucleotides from simpler precursors. In Chapter 23 we step back from our detailed look at the metabolic pathways—as they occur in all organisms, from Escherichia coli to humans—and consider how they are regulated and integrated in mammals by hormonal mechanisms. 

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each halfreaction is an a cleavage which leads to a thiamin- bound enamine (center, Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step b followed by a in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an a4 tetramer and one with an ( P)2 quaternary structure. The isolation of ohydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate52 provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase126 in the biosynthesis of the plant hormone indoIe-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25).1243/127... 

Lipid peroxidation has often been regarded simply as an undesirable side reaction, but it is also a normal part of metabolism. Initiated by enzymatically generated radicals, peroxidation occurs as specific metabolic pathways, such as the arachidonate cascade, which leads to a variety of local hormones and other substances (Eq. 21-16).254 2563... 

Adrenal Conical Hormones. The adrenal gland is made up of two parts, the medulla and the cortex, each of which secretes characteristic hormones. The hormones of the adrenal medulla art- the catecholamines, epinephrine adrenalin and norepinephrine (noradrenalint. which are closely related chemically, dil lning only in that epinephrine has an added methyl group. See Table I. In fact, animal experiments have established a metabolic pathway lor Ihe biosynthesis of both compounds Irom Ihe ammo acid pheny lal.inine. which involves enzy malic oxidation and decarboxylation reactions It is also to he noted ihui the isomeric form of norepinephrine is most important the natural D-lonn (which incidentally, is levorntatory) has many times die uciiviiy of die synthetic isomer. Epinephrine has a pronounced action upon the circulatory system, increasing both blood... 

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