Malic enzymes

Enzymes Ribonnclease Trypsin Phosphofrncto kinase Alcohol dehydrogenase Catalase Malic enzyme... 

Finally, citrate can be exported from the mitochondria and then broken down by ATP-citrate lyase to yield oxaloacetate and acetyl-CoA, a precursor of fatty acids (Figure 20.23). Oxaloacetate produced in this reaction is rapidly reduced to malate, which can then be processed in either of two ways it may be transported into mitochondria, where it is reoxidized to oxaloacetate, or it may be oxidatively decarboxylated to pyruvate by malic enzyme, with subse-... 

FIGURE 20.24 Phosphoenolpyruvate (PEP) carboxylase, pyrnvate carboxylase, and malic enzyme catalyze anaplerotlc reactions, replenishing TCA cycle Intermediates. 

PEP carboxylase occurs in yeast, bacteria, and higher plants, but not in animals. The enzyme is specifically inhibited by aspartate, which is produced by transamination of oxaloacetate. Thus, organisms utilizing this enzyme control aspartate production by regulation of PEP carboxylase. Malic enzyme is found in the cytosol or mitochondria of many animal and plant ceils and is an NADPIT-dependent enzyme. 

FIGURE 24.22 The malic enzyme reaction proceeds by oxidation of malate to oxaloace-tate, followed by decarboxylation to yield pyruvate. 

NADPH can be produced in the pentose phosphate pathway as well as by malic enzyme (Figure 25.1). Reducing equivalents (electrons) derived from glycolysis in the form of NADH can be transformed into NADPH by the combined action of malate dehydrogenase and malic enzyme ... 

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. 

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

Both dehydrogenases of the pentose phosphate pathway can be classified as adaptive enzymes, since they increase in activity in the well-fed animal and when insulin is given to a diabetic animal. Activity is low in diabetes or starvation. Malic enzyme and ATP-citrate lyase behave similarly, indicating that these two enzymes are involved in lipogenesis rather than gluconeogenesis (Chapter 21). 

Figure 5 Model of phosphorus (P) deficiency-induced physiological changes associated with the release of P-mobilizing root exudates in cluster roots of white lupin. Solid lines indicate stimulation and dotted lines inhibition of biochemical reaction sequences or mclaholic pathways in response to P deliciency. For a detailed description see Sec. 4.1. Abbreviations SS = sucrose synthase FK = fructokinase PGM = phosphoglueomutase PEP = phosphoenol pyruvate PE PC = PEP-carboxylase MDH = malate dehydrogenase ME = malic enzyme CS = citrate synthase PDC = pyruvate decarboxylase ALDH — alcohol dehydrogenase E-4-P = erythrosc-4-phosphate DAMP = dihydraxyaceConephos-phate APase = acid phosphatase.

Mitochondria from body wall muscle and probably the pharynx lack a functional TCA cycle and their novel anaerobic pathways rely on reduced organic acids as terminal electron acceptors, instead of oxygen (Saz, 1971 Ma et al, 1993 Duran et al, 1998). Malate and pyruvate are oxidized intramitochondrially by malic enzyme and the pyruvate dehydrogenase complex, respectively, and excess reducing power in the form of NADH drives Complex II and [3-oxidation in the direction opposite to that observed in aerobic organelles (Kita, 1992 Duran et al, 1993 Ma et al,... 

The reactions that convert pyruvate to intermediates of the TCA cycle are called the anaplerotic reactions. Pyruvate, which can be made only from glucose or some of the amino acids, can be converted to oxaloacetate by the enzyme pyruvate carboxylase or to malate by malic enzyme. 

Mitochondrial malic enzyme Ubiquitous mitochondrial creatine kinase... 

McKenna, M. C., Tildon, J. T., Stevenson, J. H., Huang, X. and Couto, R. Regulation of mitochondrial and cytosolic malic enzymes from cultured rat brain astrocytes. Neurochem. Res. 20 1491-1501 1995. 

Fig. 16. Ferredoxin (Fd)/ferredoxin-NADP+-reductase (FNR) mediated enzymatic carboxylation of pyruvic acid to form malic acid catalyzed by the NADPH-dependent malic enzyme (ME)...

The generalization that the same dehydrogenase has the same stereospecificity, no matter what the source of the enzyme, has been tested now particularly well for malic and lactic dehydrogenases. In fact, one can venture a guess, that pyridine nucleotide dehydrogenases which oxidize a-hydroxycarb oxylic acids at the a-position, all have A stereospecificity for the pyridine nucleotide, regardless of their stereo-specificity for the substrate. Biellman and Rosenheimer 88> have assembled the data. One can add liver malic enzyme 90> to their list. 

The practical usefulness of Equations 11.46 through 11.53 has been demonstrated for the malic enzyme catalyzed conversion of L-malate to pyruvate (Equation 11.72). Table 11.1 lists experimentally determined isotope effects for this reaction. Comparison of carbon kinetic isotope effects for protio and deutero-malate substituted at position 2 (the carbon that undergoes sp3 to sp2 transition) rules out the possibility that the hydride transfer and the decarboxylation events are concerted. This conclusion follows from Equation 11.48 which, for a concerted reaction, predicts that 13(V/K) should be smaller than 13(V/K)D, which is opposite to the order observed experimentally. 

Table 11.1 Isotope effects on malic enzyme catalyzed conversion of L-malate to Isotope effect Experimental value...

Fig. 11.8 Equilibrium perturbation trace for deuterated L-malate reaction catalyzed by malic enzyme. The equilibrium perturbation technique is discussed in Section 7.1.4. The label on the ordinate, p,M has been recalculated from the change in absorbance of TPNH at 340 nm (Schimerlik, M. I., Rife, J. E. and Clcland, W. W. Biochemistry 14, 5347 (1975))...

NAD-malic enzyme, hydride transfer from C2 of malate to NAD or APAD, concomitant with decarhoxylation. 

Karsten, W.E., Hwang, C.C. and Cook, P.F. (1999). Alpha-secondary tritium kinetic isotope effects indicate hydrogen tunneling and coupled motion occur in the oxidation of L-malate by NAD-malic enzyme. Biochemistry 38, 4398-4402... 

Karsten, W.E., Gavva, S.R., Park, S.H. and Cook, P.E. (1995). Metal ion activator effects on intrinsic isotope effects for hydride transfer from decarboxylation in the reaction catalyzed by the NAD-malic enzyme from Ascaris suum. Biochemistry 34, 3253-3260... 

NAD-malic enzyme, 52t pentaerithyritol tetranitrate (PETN) reductase, 50t... 

NAD-malic enzyme, 52t, 62-63 A,A-dimethyl-2-(aminomethyl)phenyl benzylselenoxide, 103 A,A-dimethyl-2-(aminomethyl)phenyl bromotelluronium iodide, 91 A,A-dimethyl-2-(aminomethyl)phenyl iodotelluronium iodide, 91 A,A-dimethyl-2-(aminomethyl)phenyl phenyltelluride, 110 Non-covalent molecular structures... 

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