Malate oxidation

How many of the 14 NADPH needed to form one palmitate (Eq. 25.1) can be made in this way The answer depends on the status of malate. Every citrate entering the cytosol produces one acetyl-CoA and one malate (Figure 25.1). Every malate oxidized by malic enzyme produces one NADPH, at the expense of a decarboxylation to pyruvate. Thus, when malate is oxidized, one NADPH is produced for every acetyl-CoA. Conversion of 8 acetyl-CoA units to one palmitate would then be accompanied by production of 8 NADPH. (The other 6 NADPH required [Eq. 25.1] would be provided by the pentose phosphate pathway.) On the other hand, for every malate returned to the mitochondria, one NADPH fewer is produced. 

In mitochondria, the allelochemlcals acted primarily as electron transport inhibitors. Malate oxidation was more sensitive than either succinate or NADH oxidation. No evidence for interaction with a specific membrane complex was obtained. Instead, Inhibition of substrate oxidation seems to result from alterations and perturbations produced in the inner membrane as reflected in interference with the behavior of transport processes. The compounds did not act as uncouplers or directly inhibit ATP synthesis. However, naringenin, some of the flavones, and the cinnamic acids dj inhibit the hydrolysis of ATP catalyzed by mitochondrial Mg -ATPase. 

TCA cycle Oxidation of isocitrate, a-ketoglutarate, and malate Oxidation of succinate GDP GTP +6 +2 +2... 

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.)...

The observed alterations possibly inOience lipid-protein relation and thns alter the activity of the enzymes associated with the membrane. Indeed, IW lesnlts in a decrease of the maximal rates of NAD-dependent substrates oxidation. The rate of the pair glutamate + malate oxidation in the presence of uncoupling agent (FCCP) drops from 70.0 4.6 down to 48.9 3.2 ng oxygen atom/mg of protein min and the respiratory control rate (RCR) decreases from 2.27 0.1 to 1.7 0.2 (Table 2). 

C-glucose and C-malate oxidation was greater in the light than in darkness in albino part of leavesCPig.1,2). 

I was able to obtain malate oxidation either in dialyzed yet concentrated kidney cortex extracts or by a very reproducible technique with kidney brei washed 3 to 4 times with distilled water and then extracted with phosphate. The phosphate extract was incubated with malate in the presence of fluoride. Glucose was not added. Malate underwent oxidation and phosphopyruvate accumulated.< > >... 

The low rate of oxidation of malate and fumarate is somewhat surprising. It is likely to be connected with the fact that under some conditions the oxidation of malate is inhibited by oxalacetate, presumably by competition for the enzyme. - Unless oxalacetate is removed, e.g., by decarboxylation or by condensation with active acetate, the rate of malate oxidation can be retarded. 

Narvaez Villarrubia CW, Rincon RA, Radhakrishnan VK, Davis V, Atanassov P. Methylene green electrodeposited on SWNTs-based bucky papers for NADH and L-malate oxidation. ACS Appl Mater Interfaces 2011 3(7) 2402-2409. 

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