Glycerol-3-phosphate dehydrogenase cytoplasmic

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

The ratio [NAD+]/[NADH] appears to be maintained at a relatively constant value and in equilibrium with a series of different reduced and oxidized substrate pairs. Thus, it was observed that in the cytoplasm of rat liver cells, the dehydrogenations catalyzed by lactate dehydrogenase, sn-glycerol 3-phosphate dehydrogenase, and malate dehydrogenase are all at equilibrium with the same ratio of [NAD+]/[NADH].166 In one experiment rat livers were removed and frozen in less than 8 s by "freeze-clamping" (Section L,2) and the concentrations of different components of the cytoplasm determined167 the ratio [NAD+] / [NADH] was found to be 634, while the ratio of [lactate]/[pyruvate] was 14.2. From these values an... 

The lipid-soluble ubiquinone (Q) is present in both bacterial and mitochondrial membranes in relatively large amounts compared to other electron carriers (Table 18-2). It seems to be located at a point of convergence of the NADH, succinate, glycerol phosphate, and choline branches of the electron transport chain. Ubiquinone plays a role somewhat like that of NADH, which carries electrons between dehydrogenases in the cytoplasm and from soluble dehydrogenases in the aqueous mitochondrial matrix to flavoproteins embedded in the membrane. Ubiquinone transfers electrons plus protons between proteins within the... 

Electrons from succinate are transferred to FAD in complex n and several Fe-S centers and then to UQ. Electrons from cytoplasmic NADH are transferred to UQ via a pathway involving glycerol-3-phosphate and the flavoprotein glycerol-3-phosphate dehydrogenase (see p. 316). Fatty acids are oxidized as coenzyme A derivatives. Acyl-CoA dehydrogenase, one of several enzymes in fatty acid oxidation, transfers 2 electrons to FAD. They are then donated to UQ. 

Fig. 17.1. Metabolism of glycerol. 17.i, Glycerol kinase cGPDH (NAD)y cytoplasmic NAD-linked glycerol-3-phosphate dehydrogenase mGPDH (FAD), mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase. Dihydroxyacetone-phosphate is an intermediate in the glycolytic pathway as well as a precursor for plasmalogens...

The oxidation of L-glycerol 3-phosphate to dihydroxyacetone phosphate is catalyzed by two different enzymes. One is the cytoplasmic NAD-linked a-glycerophosphate dehydrogenase, and the other is the mitochondrial enzyme, which appears to contain flavin and iron. The latter enzyme was first studied by Green in 1936 (223). It was shown to be associated with respiratory particles, and widely distributed in animal tissues. The highest concentration of the enzyme was found in the brain. Lardy and co-workers (234) studied the enzyme in deoxycholate-solubilized particles obtained from skeletal muscle, confirmed the finding... 

Glycerol 3-phosphate shuttle for the transport of cytoplasmic reducing equivalents to the inner mitochondrial membrane. Glycerol 3-phosphate, which carries the reducing equivalents, is oxidized to dihydroxyacetone phosphate by an FAD-linked dehydrogenase located on the C side of the inner membrane. 

In the cytoplasm, oxaloacetate is reduced by NADH to malate via cytoplasmic malate dehydrogenase. Malate can pass into the mitochondrial matrix via special dicarboxylic acid transporters that are in the inner mitochondrial membrane. Once in the matrix, oxaloacetate is reoxidized to malate by mitochondrial malate dehydrogenase. Thus this series of enzyme and transporter reactions has effectively shuttled reducing equivalents in NADH from the cytoplasm to the matrix. This shuttle constitutes the most efficient way of transferring hydrogen atoms from NADH in the cytoplasm to the mitochondrial matrix, and hence into the electron transport chain (see Sec. 10.12 for the glycerol 3-phosphate shuttle). 

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