By Leon E. Rosenberg (auth.), Harry Harris, Kurt Hirschhorn (eds.)
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Extra info for Advances in Human Genetics 6
26 It is now believed that this compound, formed by two sequential hydroxylations in two different organs, then circulates to gut and skeleton, where it enhances calcium absorption and mobilization, respectively. Chapter 1: Vitamin-Responsive Metabolic Disorders 37 Acquired and Inherited Rickets The skeletal disorder known as rickets was described in the seventeenth century, long before any appreciation of the existence of vitamin D or its effect on bone mineral metabolism. 116 In the eighteenth century, cod liver oil was being prescribed for rachitic patients, but 200 years were to elapse before it was learned that sunlight and fish liver oil were both acting to restore the normal tissue content of a sterol which we now recognize as vitamin D.
4, hydroxocobalamin (OH- Chapter 1: Vitamin-Responsive Metabolic Disorders 19 Cbl) is the precursor vitamin and exists with its cobalt atom oxidized to a trivalent state (C 0 3+). OH-Cbl is reduced successively to Cbl II (Co2+) and Cbl I (Co+) by reductase enzymes, which are flavoproteins requiring N AD as a cofactor. Cbl I is then converted enzymatically to Ado-Cbl by a third enzyme called ATP:Cbl I 5'-deoxyadenosyltransferase. The precise chemical reactions involved in Me-Cbl synthesis have not been defined but are presumed to follow those shown for Ado-Cbl during the reductase steps.
PLP has , been shown to have a much greater affinity for some apoenzymes than others. Thus its affinity for transaminases far exceeds that for decarboxylases or kynureninase. These differences in affinity are reflected in the enzymatic dysfunctions seen in pyridoxine deficiency states. Pyridoxine Deficiency Pyridoxine deficiency is rare but has been observed in several settings in which the total tissue pool of PLP and its precursors is reduced. 135 Dietary insufficiency has been reported in infants after prolonged breast feeding by malnourished mothers, and in children and adults with inadequate general nutrition.