Transhydrogenases

A Proton-Translocating Transhydrogenase Is a Source of Intramitochondrial NADPH... 

Energy-linked transhydrogenase, a protein in the inner mitochondrial membrane, couples the passage of protons down the electrochemical gradient from outside to inside the mitochondrion with the transfer of H from intramitochondrial NADH to NADPH for intramitochondrial enzymes such as glutamate dehydrogenase and hydroxylases involved in steroid synthesis. 

Figure 22-4. Sequence of reactions in the oxidation of unsaturated fatty acids, eg, linoleic acid. A -c/s-fatty acids or fatty acids forming A -c/s-enoyl-CoA enter the pathway at the position shown. NADPH for the dienoyl-CoA reductase step is supplied by intramitochondrial sources such as glutamate dehydrogenase, isocitrate dehydrogenase,and NAD(P)H transhydrogenase.

The reversibility of reaction (8) has not been observed as yet (H20, M3, R4) and may be attributed to other systems (M2), such as assumed by Racker (R2), the oxidation of GSH to GSSG being coupled to the reduction of homocystine under control of a transhydrogenase. 

R2. Racker, E., Glutathione-homocystine transhydrogenase. ]. Biol. Chem. 217, 867-874 (1955). 

Middleditch, L. E., Chung, A. E. Pyridine nucleotide transhydrogenase from Azotobacter vinelandii cells Stereospecificity of hydrogen transfer. Arch. Biochem. Biophys 146, 449—453 (1971). 

Hydride Transfer in NAD+- and NADP -Dependent Enzymes. The transfer of the hydride ion in redox reaction of NAD+- and NADP+-dependent enzymes can occur either to the re- or the xi-face of the pyridine ring of the coenzyme . Such stereochemistry is crucial in the characterization of these enzymes. The same enzymes from different sources can express different stereospecificities. For example, E. coli NAD(P)+ transhydrogenase expressed one form of stereospecificity whereas the Pseudomonas aeruginosa enzyme catalyzes the identical reaction with the other NAD form . 

A major class of enzymes that catalyze oxidation-reduction reactions. This class includes dehydrogenases, reductases, oxygenases, peroxidases, and a few synthases. Examples include alcohol dehydrogenase (EC 1.1.1.1), aldehyde oxidase (EC 1.2.3.1), orotate reductase (EC 1.3.1.14), glutamate synthase (EC 1.4.1.14), NAD(P) transhydrogenase (EC 1.6.1.1), and glutathione peroxidase (EC 1.11.1.9). 

This enzyme [EC 1.8.4.2], also known as glutathione insulin transhydrogenase and insulin reductase, catalyzes the reaction of two glutathione with a disulfide bond in a protein to produce glutathione disulfide and a protein with two new thiol groups. The enzyme can reduce insulin and a number of other proteins. 

Nicotinamide nucleotide transhydrogenase, NADfPj TRANSHYDROGENASE NICOTINAMIDE PHOSPHORIBOSYLTRANS-FERASE... 

ALCOHOL DEHYDROGENASE Pyridine nucleotide transhydrogenase, NAD(Pr TRANSHYDROGENASE PYRIDOXAL 4-DEHYDROGENASE PYRIDOXAL KINASE... 

Mercer NA, McKelvey JR, Fioravanti CF (1999) Hymenolepis diminuta catalysis of transmembrane proton translocation by mitochondrial NAD PHONAL) transhydrogenase. Exp Parasitol 91 52-58... 

Youssef NN, Hammond D (1971) The fine structure of the developmental stages of the microsporidian Nosema apis Zander. Tissue Cell 3 283-294 Yu Y, Samuelson J (1994) Primary structure of an Entamoeba histolytica nicotinamide nucleotide transhydrogenase. Mol Biochem Parasitol 68 323-328 Zheng L, Cash VL, Hint DH, Dean DR (1998) Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J Biol Chem 273 13264-13272... 

In discussion of nomenclature of malic acid decomposing enzymes, mention should be made of malate-lactate transhydrogenase. This enzyme, isolated from Micrococcus lactiyticus (VielloneUa alcalescens), a bacterium found in vertibrates, can catalyze reversibly the conversion of L-malic and pyruvic acids to L-lactic and oxaloacetic acids with NAD as coenzyme (36). 

Action of Malate-Lactate Transhydrogenase, J. Biol. Chem. (1972) 247, 90 -916. 

Another energy-linked process is the transhydro-genase reaction by which NADH reduces NADP+ to form NADPH. In the cytoplasm various other reactions are used to generate NADPH (Chapter 17, Section I), but within mitochondria a membrane-bound transhydrogenase has this function.283-2863 It couples the transhydrogenation reaction to the transport of one (or possibly more than one) proton back into the mitochondria (Eq. 18-14). A value of Ap of -180 mV could increase the ratio of [NADPH] / [NADP+] within mitochondria by a factor of as much as 1000. 

Transhydrogenases function in a similar way within bacteria. Whether from E. coli, photosynthetic bacteria, or bovine mitochondria, transhydrogenases have similar structures.285 Two 510-residue a subunits associate with two 462-residue P subunits to form an OC2P2 tetramer with 10-14 predicted transmembrane helices. Tire a subunits contain separate NAD(H) and NADP(H) binding sites. A conformational change appears to be associated with the binding or release of the NADP+ or NADPH 287... 

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