Transhydrogenase systems

Malic enzyme, fumarate reductase and transhydrogenase systems in the mitochondria of adult Spirometra mansonoides (Cestoda). Journal of Experimental Zoology, 206 167-77. 

ATP 6CO2 -I- 12NADPH + 12H + ADP + P. The importance of the P.p.c. lies in the production of reduced NADPH which is required for biosynthesis (e.g of fatty acids), and in the production of pentoses required for the synthesis of nucleosides, nucleotides and nucleic adds. By the action of a transhydrogenase system, or NADPH cytochrome c reductase, the NADPH can be reoxidized to produce energy (36 molecules ATP per molecule glucose), but operation of the P.p.c. for the sole purpose of energy production is unusual. 

In the transhydrogenase system, all components for the assay are present except estradiol dehydrogenase and steroid. Addition of aflSnity labeled estradiol dehydrogenase to the assay mixture simultaneously introduces the potential catalytic agents, enzyme (either native or modified) and steroid (estrone covalently linked to estradiol dehydrogenase). 

Colowick has pointed out that this transhydrogenase system may provide a shuttle when and where necessary for linking DPN-specific dehy-... 

It suggested that the reversible oxidation and reduction of the steroids themselves constituted a steroid-activated transhydrogenase system according to equation (1). The net effect is the transfer of hydrogen from TPNH... 

Finally, at the level of enzymatic reactions, the effect of estrogens upon the transhydrogenase system present in several estrogen-sensitive tissues has provided the springboard for speculations concerning the intimate mechanism of action of these substances. It would be premature to say that we had any real understanding of these mechanisms, but the widespread interest evoked in this area will undoubtedly lead to a rapid accumulation of information and a deeper insight into this problem. 

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. 

Fig. 5.9. Proposed scheme for the intramitochondrial metabolism of malate by Hymenolepis diminuta. Abbreviations ME, malic enzyme F, fumarase T, transhydrogenase FR, fumarate reductase ETS, electron transport system. Once within the matrix compartment, malate oxidation, as catalysed by malic enzyme, results in NADPH formation. Via the activity of fumarase, malate also is converted to fumarate in the matrix compartment. NADPH then serves as a substrate for the inner-membrane-associated transhydrogenase and transhydrogenation between NADPH and matrix NAD is a scalar reaction associated with the matrix side of the inner membrane. Matrix NADH so formed reduces the electron transport system via a site on the matrix side of the inner membrane permitting fumarate reductase activity. The reduction of fumarate to succinate results in succinate accumulation within the matrix compartment. (After McKelvey Fioravanti, 1985.)...

Nicotinamide nucleotide transhydrogenases may be divided into two classes. One class is present in certain bacteria, and possibly in some plants, is an easily extractable, water-soluble enzyme is not functionally linked to the energy-transfer system of the bacterial membrane is a fiavoprotein and is specific for the 4B-hydrogen atom of both NADH and NADPH. The other class is present in both certain bacteria and in mitochondria is a firmly membrane-bound water-insoluble enzyme is functionally linked to the energy-transfer system of the bacterial or mitochondrial membrane is not known to be a flavoprotein and is specific for the 4A-hydrogen atom of NADH and the 4B-hydrogen atom of NADPH. For the sake of convenience, the two classes of enzyme will be referred to below as BB-specific and AB-specific transhydrogenases, respectively. 

Assay of AB-specific transhydrogenase is principally identical to that of BB-specific transhydrogenase (see Section II,C) i.e., with the natural nicotinamide nucleotides, an enzymic regenerating system is used to keep the concentration of one of the substrates constant (30, SB, 66-68, 66)... 

AB-Specific transhydrogenases are functionally coupled to the energy-transfer system of the membrane in which they are located. This coupling... 

As pointed out by Krebs and Veech (176), the relationship between the redox states of NAD and NADP in mammalian cells would be governed to a large extent by the substrate levels of NAD- and NADP-dependent dehydrogenases, interlinked by shared reactants. The coordination of these systems of interlinked dehydrogenases and, in particular, energy-linked transhydrogenase has been a matter of controversy. Funda-... 

NADH dehydrogenase and, 189 ubiquinone reductase and, 178,182,183 Cholesterol, side chain cleavage, 83, 84-85 Choline, oxidation to betaine, 260 Choline dehydrogenase electron transport system and, 261-263 properties, 260-201 Chromatium sulfate reduction by, 281 transhydrogenase of, 54 function of, 80 molecular properties, 58, 69 purification, 55, 56 Chromium... 

---