Phosphate-metabolising enzymes

The pseudohalide azide inhibits VCIPO. The first stmcturally characterised VHPO had in fact been crystallised in its azide-inhibited form. Inhibition has also been noted with hydroxylamine and hydrazine. Further, structural analogues of vanadate, such as [ALF4] and phosphate, are potent inhibitors. In turn, vanadate inhibits many phosphatases (and other phosphate-metabolising enzymes). On the other hand, apo-VHPOs can exhibit some phosphatase activity, and vanadate-inhibited phosphatases show some haloperoxidase activity. These phenomena will be discussed in Section 5.2.1. 

The original discovery leading to our present interest in pyridoxal-P-dependent biological reactions was made in 1934 by Paul Gyorgy [1] in the United States (Western Reserve University, Cleveland). He identified a nutritional factor that could cure a specific dermatitis produced in young rats when they were reared on a deficient diet. Gyorgy called this factor vitamin which was subsequently shown to be pyridoxine (Fig. 1,1). The term vitamin is currently used to include a number of closely related substances of dietary origin (Fig. 1,1,2 and 3), which, in animals, are metabolised to produce the enzymically active form, pyridoxal phosphate (Fig. 1, 5). The pathways for these transformations [2] are shown in Fig. 1. 

Cholesterol is made in the liver from glucose via the pentose phosphate pathway (which generates NADPH) and glycolysis, which produces acetyl CoA (Fig. 38.1). Acetyl Co A is then metabolised to 3-hydroxy-3-methylglutaryl CoA (HMGCoA) which is reduced by NADPH in the presence of HMGCoA reductase (the regulatory enzyme for cholesterol synthesis) to form mevalonate. Mevalonate is then metabolised via more than two dozen intermediates (not shown) to form cholesterol. 

In 1934 it was shown that yeast and mammalian muscle contain an enz3rme aldolase) which splits this fructose-l-6-diphosphate between carbon atoms 3 and 4 to give triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone phosphate). The same enzyme was, by 1949, shown to be universally distributed in higher plants. Further, the two isomeric triosephosphates formed are interconvertible by means of a second enzyme, phosphotriose isomerase. This is important because it is only the glyceraldehyde-3-phosphate which is normally further metabolised in respiration. 

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