Cleavage mechanisms hormones

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... 

The coupling reaction by which the aromatic group from one residue of mono- or diiodotyrosine is joined in ether linkage with a second residue is also catalyzed readily by peroxidases. One dehydroalanine residue is formed for each molecule of hormone released.108 A possible mechanism involves formation of an electron-deficient radical, which can undergo (3 elimination to produce a dehydroalanine residue and an aromatic radical. The latter could couple with a second radical to form triiodothyronine or thyroxine. However, as depicted in Eq. 25-6, the radical coupling may occur prior to chain cleavage. While P elimination (pathway... 

Photodegradation. UV/Vis exposure can induce protein oxidation, aggregation, and backbone cleavage. For example, oxidation has been observed in the histidine residue of human growth hormone (hGH) exposed to photostability conditions (6.7 x 106 lux hours). The proposed oxidation mechanism and product is shown in Figure 136. 

Although cholesterol is accepted as the major precursor of steroid hormones as a result of side-chain cleavage to pregnenolone (see below), research over the past decade or so has focused on the mechanisms by which steroidogenic tissues obtain cholesterol. It should be borne in mind that such tissues require cholesterol, not only for steroid synthesis but also for membrane synthesis, and hence require more of the precursor sterol than other tissues. Morris and Chaikoff [1] showed that the bulk of rat adrenal cholesterol was derived from circulating cholesterol, and later work revealed a similar state of affairs in humans. 

Hydroperoxide lyases catalyse the cleavage of the C-C single bond that is adjacent to the peroxy group. In the case of 13-HpOTrE, the C-12-C-13 bond is cleaved, yielding an unsaturated aldehyde and (9 )-12-oxo-9-dodecenoic acid, which is a precursor of the wound hormone traumatin (Scheme 10). The volatile aldehydes formed via the peroxide lyase pathway exhibit bactericidal properties and are emitted by plants in response to wounding. Thus they may be regarded as part of the plant s disease resistance mechanisms [53]. 

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