Download Advances in Human Genetics 6 by Leon E. Rosenberg (auth.), Harry Harris, Kurt Hirschhorn PDF

By Leon E. Rosenberg (auth.), Harry Harris, Kurt Hirschhorn (eds.)

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10). They showed that massive doses of ergocalciferol, cholecalciferol, or 25-hydroxycholecalciferol were required to heal the rachitic lesions whereas physiological doses of 1, 25dihydroxycholecalciferol promptly initiated healing. These results, although as yet unsupported by in vitro observations, suggest a defect in the renal hydroxylating enzyme which catalyzes the final conversion of 25-hydroxycholecalciferol to its dihydroxy form. This postulate would place vitamin D dependent rickets in precisely the same category of illness as noted earlier for certain cobalamin- and folateresponsive conditions-namely one in which a specific block in vitamin activation leads to failed synthesis of coenzyme or, in the case of vitamin D, of active hormone.

The centered scheme depicts the sequence of enzymatic reactions required for conversion of the vitamin hydroxocobalamin (OH-CBL) to its active coenzymes, 5'deoxyadenosylcobalamin (ADO-CBL) and methylcobalamin (ME-CBL). The broken line leading to ME-CBL reflects uncertainty concerning the point of divergence of its biosynthetic pathway from that leading to ADO-CBL formation. At the top and bottom, the two enzymatic reactions dependent on cobalamin coenzymes are also shown: methylmalonylCoA mutase and N5- methyltetrahydrofolate-homocysteine methyltransferase.

3). It has two characteristic components. The first, and most characteristic, is a planar corrin ring system containing four pyrrole rings each coordinated through its nitrogen atom to a central cobalt nucleus. The second is a dimethylbenzimidazole ribotide portion extending down from the plane of the corrin ring. 57 The molecule is completed by coordinate linkage of one of several different radicals to the cobalt atom. This radical extends up from the corrin plane. Thus cyanocobalamin (CNCbI), the commercial form of vitamin B 12 , is formed by attachment of a cyanide radical to the cobalt atom.

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