Liver glyceraldehyde-3-phosphate dehydrogenase

Zinc is essential for the functioning of at least twenty different enzymes, and their functions are widely varied. They include the alcohol dehydrogenases of yeast and mammalian liver, glyceraldehyde phosphate dehydrogenase, phosphoglycomutase of yeast, DNA and RNA polymerases (at least in bacteria), alkaline phosphatase in bacteria, mammalian carbo-xypeptidase, carbonic anhydrase, AMP hydrolase, pyruvate carboxylase (yeast), and aldolase (yeast and bacteria). The alkaline phosphatase of E, coli has, in each molecule, four atoms of zinc the two which maintain structure can be replaced by Mn, Co +, or Cu, whereas the other two atoms are essential for enzyme action (Trotman and Greenwood, 1971). 

Brune and Lapetina (1989) reported that NO could activate a platelet ADP-ribosyltransferase that resulted in the ribosylation of a 39 kDa protein. Subsequent work revealed that the protein was glyceraldehyde phosphate dehydrogenase (GAP-DH), and that ribosylation was associated with reduced GAP-DH activity (Dimmeler et al., 1992). In our collaboration with Molina et al., (1992), we have shown that GAP-DH activity is dramatically inhibited in C. parvum treated rats and that this action is associated with both a ribosylation and nitro-sylation of the enzyme. Such a marked inhibition of a glycolytic enzyme could explain some of the metabolic changes observed in the liver in sepsis. 

Phosphofructokinase, the enzyme that phosphory-lates fructose-1-phosphate to yield the diphosphate, the precursor of the triose phosphates, has a fate similar to that of hexokinase, except that its prenatal activity is only three times greater than that of adult liver, and the prenatal activity drops to adult values within 9 days after birth. Fructose-1,6-diphosphate, triose-P-isomerase, and glyceraldehyde phosphate dehydrogenase all have high fetal activities that slightly increase at the adult levels in the newborn. Thus, in the fetal liver the activity of these enzymes seems to favor the formation rather than the use of lactic acid. 

Gregus, Z. and Nemeti, B. (2005) The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase works as an arsenate reductase in human red blood cells and rat liver cytosol. Toxicological Sciences, 85(2), 859-69. 

A compound is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase. If this compound were added to liver cells where o-glucose was the only substrate, what effect would it have on the concentrations of the glycolytic intermediates ... 

Fig. 35. Diagrammatic representation of functionally equivalent groups around the substrate in lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and horse liver alcohol dehydrogenase. From the work of Rossmann and colleagues [164],...

Nicotinamide-(S-methylmercury-thioinosine) dinucleotide was found to exhibit coenzyme properties with lactate dehydrogenase and liver alcohol dehydrogenase, but inactivate yeast alcohol dehydrogenase and glyceraldehyde 3-phosphate dehydrogenase an essential thiol group was therefore modified in the last two cases. 

The administration of TNT to laboratory animals leads to the excretion of 4-NHOH-DNT, 2-NH2-DNT, and 4-NH2-DNT in the urine [59], and to the formation of covalent adducts with microsomal liver and kidney proteins, hemoglobin, and other blood proteins [60], The acid hydrolysis of adducts yielded mainly 2-NH2-DNT (2-ADNT) and 4-NH2-DNT (4-ADNT). Incubation of rat liver microsomes with TNT and NADPH under aerobic conditions resulted in the formation of NH2-DNTs and the transient metabolite 4-NHOH-DNT [57], The formation of covalent protein adducts with TNT metabolites was enhanced by the presence of 02 and decreased by GSH. This is consistent with the scheme of the TNT adduct formation with the central role of the nitroso metabolite (NO-DNT) reaction with protein or nonprotein thiols (RSH Equation 9.11) [57], The acid hydrolysis of the sulfinamide adduct (RS(0)-NH-DNT) formed after the rearrangement of the semimercaptal (RS-N(OH)-DNT Equation 9.12) will yield NH2-DNT. The mixture of NHOH-DNTs inhibits bacterial glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase more efficiently than TNT [61]. This was attributed to the covalent modification of protein -SH groups. 

The fate of dihydroxyacetone phosphate is also varied—it may be transformed to a-glycerophosphate, or through the reaction catalyzed by the triose isomerase, it may yield D-glyceraldehyde-3-phosphate, which in the presence of triose phosphate dehydrogenase and phosphoglycerate kinase yields 3-phosphoglycerate. This degradation pathway is complete only in liver, and it is not known to what extent it operates in muscle. 

The relatively unhindered domain motion in immunoglobulins may be contrasted with that observed in some enzymes, in which the domain motion occurs upon substrate binding during the catalytic cycle. The phenomenon has been established by crystal structure analysis of the different forms of yeast hexokinase [11], liver alcohol dehydrogenase [12] and citrate synthase [13], and appears to occur also in glyceraldehyde-3-phosphate-dehydrogenase. 

On the other hand, a number of native proteins tested were found to be better substrates for cathepsin M than for cathepsin B (Table IV). Muscle and liver aldolases were inactivated by cathepsins M and B at comparable rates (Table IV) but yeast glucose-6-phosphate dehydrogenase was inactivated much more rapidly by cathepsin M and neither rabbit liver pyruvate kinase nor rabbit muscle glyceraldehyde-3-phosphate dehydrogenase was inactivated on incubation with cathepsin B. 

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