Citric acid cycle fumarase

Steps 7-8 of Figure 29.12 Hydration and Oxidation The final two steps in the citric acid cycle are the conjugate nucleophilic addition of water to fumarate to yield (S)-malate (L-malate) and the oxidation of (S)-malate by NAD+ to give oxaloacetate. The addition is cataiyzed by fumarase and is mechanistically similar to the addition of water to ris-aconitate in step 2. The reaction occurs through an enolate-ion intermediate, which is protonated on the side opposite the OH, leading to a net anti addition. 

The criteria for gene displacement in this study were strict. The reactions catalyzed were required to have the same EC (Enzyme Commission) number, which implies that the same cofactors had to be involved. In the example of reactions involved in the citric acid cycle given previously, when only the carbohydrate substrate and product of the reaction were the same, we could identify gene displacements at 6 of the 11 steps included in the analysis. Only two of those (malate dehydrogenase and fumarase) met the criteria in Galperin et al. (1998). 

Balance Sheet for the Citric Acid Cycle The citric acid cycle has eight enzymes citrate synthase, aconitase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, and malate dehydrogenase. 

In the second step of the /3-oxidation cycle (Fig. 17-8a), water is added to the double bond of the tran.s-A2-enoyl-CoA to form the l stereoisomer of /3-hydroxyacyl-CoA (3-hydroxyacyl-CoA). This reaction, catalyzed by enoyl-CoA hydratase, is formally analogous to the fumarase reaction in the citric acid cycle, in which H20 adds across an a-/3 double bond (p. XXX). 

Fig. 1.2 Intermediates of the citric acid cycle showing the relationship between glutamate and aspartate. Pyruvate dehydrogenase complex (1) citrate synthase (2) aconitase (3) isocitrate dehydrogenase (4) a-ketoglutarate dehydrogenase (5) succinyl-CoA synthetase (6) fumarate (7) fumarase dehydratase (8) malate dehydrogenase (9) and aspartate aminotransferase (10)...

By application of the CIP rules the order of priority of the atoms directly attached to the chirality centre is O > C(0,0,(0)) > C(C,H,H) > H. The atom or group of lowest priority, hydrogen in this case, is already oriented away from the observer. Therefore the sequence of the remaining three groups can be directly deduced from the formula, and these are easily seen to be arranged in a counter-clockwise sense to the observer. It therefore follows that the formula represents (S)-2-hydroxysuccinic acid (formerly known as L-malic acid). The compound is produced in the citric acid cycle from fumaric acid by fumarate-hydratase (fumarase). 

STEPS 7-8 Regeneration of oxaloacetate. Catalyzed by the enzyme fumarase. conjugate miclcophilic addition of w ater to fumarate yields t-malate in a reaction simUar to tliat of step 2 in the fatty acid j3>oxidation pathway. Oxida-i m with NAD then, gives oxaloacetate in a step catalyzed by malate dehydrogenase, and the citric acid cycle has return to ita starting point, ready to revolve again. 

Fumarase is an enzyme of the citric acid cycle, glyoxylate cycle, and urea cycle that catalyzes addition of water to the double bond of fumarate to form L-malate. 

Figure 2.4. Citric acid cycle. This series of reactions is catalyzed by the following enzymes as numbered in the diagram (1) Citrate synthase, (2) Aconitase, (3) Aconitase, (4) Isocitrate dehydrogenase, (5) a-Ketoglutarate dehydrogenase compiex, 6) Succinyl CoA syntetase, (7) Succinate dehydrogenase, (8) Fumarase and (9) Malate dehydrogenase. Adapted from L. Stryerl .

In the presence of fumarase (fumarate hydratase, EC 4.2.12) malate undergoes reversible dehydration to generate fumarate (citric acid cycle). In this process (a franx-elimination), the hydroxyl at C-2 and the pro-R hydrogen at C-3 are lost (Scheme 13.23). 

The conversion of oxaloacetate to succinate is catalyzed by enzymes of the citric acid cycle malate dehydrogenase, fumarase and succinate dehydrogenase. These enzymes were isolated from the cells of P. shermanii... 

Following an abrupt transition of P. pentosaceum from anaerobic to aerobic metabolism (10 pM O2), the growth rate increases at first, but the formation of acetate from lactate and glucose is slowed down, propionate formation is completely repressed and pyruvate is accumulated in the medium (van Gent-Ruijters et al, 1976 Schwartz et al, 1976). A decrease in the activities of the citric acid cycle enzymes malate dehydrogenase, fumarase and NADH oxidase, lactate oxidase, NADH-dependent fiimarate reductase, lactate-dependent nitrate reductase is observed upon the transition from anaerobic to aerobic (10 pM O2) metabolism (van Gent-Ruijters, 1975). 

Fumarase is the enzyme that catalyzes the dehydration of malate in the citric acid cycle. The citric acid cycle is a series of reactions that oxidize compounds derived from carbohydrates, fatty acids, and amino acids (Section 25.10). 

The citric acid cycle is the series of enzyme-catalyzed reactions responsible for the oxidation of the acetyl group of acetyl-CoA to two molecules of CO2. The enzymes that catalyze the reactions are 1. citrate synthase 2. aconitase 3. isocitrate dehydrogenase 4. a-ketoglutarate dehydrogenase 5. succinyl-CoA synthetase 6. succinate dehydrogenase 7. fumarase and 8. malate dehydrogenase. 

Biochemical processes are catalyzed by enzymes that have multiple stereogenic centers and are therefore chiral. Enzymes provide a chiral environment in which to form stereogenic centers. As a consequence, only one enantiomer forms firom an enzyme-catalyzed reaction, even if the reactant is achiral. For example, fumaric acid reacts with water in an addition reaction catalyzed by the enzyme fumarase in the citric acid cycle to give only (i)-malic acid. We show the carboxyhc acids as their conjugate bases because they are ionized at pH 7. These ionic compounds are called fumarate and malate. This reaction converts fumarate to (i)-malate. 

Fumarase 194,000 4 Enzymatic reaction in citric acid cycle... 

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