Hexose monophosphates dehydrogenase

Go-dehydrogenase II, co-enzyme II (Warburg), obtained from yeast and red blood cells, acts with hexose monophosphate dehydrogenase. 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Reactions of the hexose monophosphate pathway. Enzymes numbered above are 1) glucose 6-phosphate dehydrogenase and 6-phosphogluconolactone hydrolase, 2) 6-phosphogluconate dehydrogenase,... 

FMN was first identified as the coenzyme of an enzyme system that catalyzes the oxidation of the reduced nicotinamide coenzyme, NADPH (reduced NADP), to NADP (nicotinamide adenine dinucleotide phosphate). NADP is an essential coenzyme for glucose-6-phosphate dehydrogenase which catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconrc acid. This reaction initiates the metabolism of glucose by a pathway other than the TCA cycle (citric acid cycle). The alternative route is known as the phosphoglneonate oxidative pathway, or the hexose monophosphate shunt. The first step is ... 

Fig. 1. Integrated scheme showing the metabolic systems of regulation operating in eu-ryhaline Crustacea (after ref. 9). Broken lines indicate an inhibitory action of the effector and the heavy lines indicate activation. Notice the key role played by glutamic dehydrogenase as well as the controls exerted on the reactions utilizing reducing equivalents. The cAMP concentration is higher in concentrated medium than in dilute medium. The hormone responsible for this effect is not yet identified. HMPS, hexoses monophosphate shunt.

Understand the physiologic importance of the hexose monophosphate shunt and understand reactions catalyzed by glu-cose-6-phosphate and 6-phosphogluconate dehydrogenases, transaldolase, and transketolase discuss the importance of the hexose monophosphate shunt in red cell physiology. 

Figure 18.10 The hexose monophosphate shunt pathway. A, glucose-6-phosphate dehydrogenase B, 6-phosphogluconate dehydrogenase C, pentose-5-phosphate iso-merase D, pentose phosphate epimerase E, transaldolase F, transketolase G, phospho-hexoseisomerase. (Reproduced by permission from Williams JF. A critical examination of the evidence for the reactions of the pentose pathway in animal tissues. Trends Biochem Sri December 316, 1980.)...

Pyruvate dehydrogenase, especially in the adipose tissue, is stimulated by a high insulin/glucagon ratio. This leads to the production of acetyl-CoA, which may enter the Krebs cycle in the fed state. The more likely possibility is the biosynthesis of fatty acids from acetyl-CoA. The latter requires NADPH, and for this reason, the hexose monophosphate shunt is also activated. 

A total of 14 NADPH molecules are utilized to make each palmitate molecule. It comes from three sources the malic enzyme (see earlier) provides one NADPH molecule for every acetyl-CoA molecule generated from citrate. For palmitate, this accounts for eight NADPH molecules. The rest must be derived largely from the hexose monophosphate shunt (see Chapter 18). A minor source of NADPH is cytosolic isocitrate dehydrogenase (see Chapter 18). The synthesis of one palmitate molecule thus requires an equivalent of 7 + (3)14 = 49 ATP molecules. 

Glucose 6-phosphate dehydrogenase The enzyme that catalyzes the rate regulating step of the hexose monophosphate shunt, which produces NADPH required for inactivating oxygen radicals and thereby protects the RBC membrane from radical attack and rapture. 

A number of studies on the metabolism of 3FG and 4FG in Locusta miaratoria have been undertaken. Both 3FG and 4FG are toxic to locust with LD50 s of 4.8 mg/g and 0.6 mg/g respectively. In vitro studies showed that 3FG is metabolized in the fat body, via the NADP-linked aldose reductase, to 3-deoxy-3-fluoro-D-glucitol (3FGL). This metabolite was detected in the hemolymph of the insect and shown to be both a competitive inhibitor and a substrate for NAD-linked sorbitol dehydrogenase, thereby generating 3-deoxy-3-fluoro-D-fructose (3FF) (541. Subsequently, it was shown by in vivo radio-respirometric analysis of C02 and appropriate chase experiments, that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate shunt or tricarboxylic acid cycle (55). In addition, the release of fluoride ion and H20 from D-[3- H]-3FG was also observed. Based on the mechanism of aldolase (55) and triosephosphate isomerase... 

Metabolism of the hexose monophosphate shunt in glucose-6-phosphate dehydrogenase deficiency and closely interrelated reactions. 

Fig, 17.6 Hexose monophosphate pathway. 1, glucose-6-P-dehydrogenase 2, 6-P-gluconolactonase 3,6-P-gluconate dehydrogenase 4, phosphoribose isomerase 5, phosphoketopentose epimerase 6, transketolase 7, transaldolase TPP, thiamine pyrophosphate. 

The biochemistry of the lactic acid bacteria has received attention [4, 17-20]. Homofermentative strains such as the Pediococci use the glycolytic pathway for the dissimilation of carbohydrates, such as glucose, to yield pyruvic acid. Pyruvic acid acts as a hydrogen acceptor and is converted to lactic acid by means of an NADH-dependent lactic dehydrogenase. It is believed that the homofermentative strains use in addition the hexose monophosphate pathway and possibly a phosphoketolase pathway (Fig. 21.2) when pentoses are degraded. The heterofermentative strains on the other hand lack both aldolase and hexose isomerase, essential for the operation of the glycolytic pathway, while pyruvic acid will not readily function as a... 

Rossi et al., 1972). As described in figure 1, there is an increase in glucose metabolism via the dehydrogenases of the hexose monophosphate (HMP) shunt, as well as ein increase in the non-mitochondrial consiomption of (Rossi et al.,... 

Fig. 1. Pathway of fatty acid synthesis from glucose in animal tissues. The key enzymes or enzyme systems involved are (1) pyruvate dehydrogenase, (2) pyruvate carboxylase, (3) citrate synthase, (4) citrate translocation system, (5) citrate cleavage enzyme, (6) acetyl-CoA carboxylase, (7) fatty acid synthetase, (8) 3-phosphoglyceraldehyde dehydrogenase, (9) malate dehydrogenase, (10) malic enzyme, (11) hexose monophosphate shunt.

Glucose-6-P and 6-phosphogluconate dehydrogenases [46-51] of the hexose monophosphate shunt (A, Fig. 2) and malic enzyme [50-55] of the malate transhydrogenation cycle (B, Fig. 2) appear to be regulated both by variations in tissue levels and by metabolite effectors. The details of the regulation of these pathways are beyond the scope of this chapter. 

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