Dehydrogenation of malate

This also occurs in the Krebs cycle, as in the dehydrogenation of malate to oxaloacetate. 

Finally, Malate DH catalyzes the dehydrogenation of malate to regenerate the original carrier, oxaloacetate, and finish the cycle. In addition another NADH is formed (and 2 x 2.5 ATP/NADH= 5 ATP/Glucose). 

Reactions analogous to those of the TCA-cycle are found in the biosynthesis of leucine and lysine (Fig. 4). Similarly, the sequence of reactions represented by the dehydrogenation of succinate by a fla-voenzyme, followed by hydration of fumarate to ma-late, then dehydrogenation of malate by a NAD-linked dehydrogenase, finds a counterpart in the initial stages of fatty acid degradation (see). 

A key enzyme in the glyoxylate cycle is isocitrate lyase, which cleaves isocitrate (Eq. 13-40) to succinate and glyoxylate. The latter is condensed with a second acetyl group by the action of malate synthase (Eq. 13-38). The L-malate formed in this reaction is dehydrogenated to the regenerating substrate oxalo-... 

Batch Di (3-pentyl) Malate Process Acetaldehyde from Acetic Acid Ethylene by Oxidative Dehydrogenation of Ethane Butadiene to n-Butyraldehyde and n-Butanol Methacrylic Acid to Methylmethacrylate Coproduction of Ethylene and Acetic Acid from Ethane Methylmethacrylate from Propyne Mixed-C4 Byproduct Upgrade Hydrogen Peroxide Manufacture Di-tem fljy-butyl-peroxide Manufacture Vinyl Acetate Process PM Acetate Manufacture Propoxylated Ethylenediamine Petroleum Products Fuel Additives for Cleaner Emissions Gas Manufacture... 

The NAD(P)H is regenerated by dehydrogenation of malic acid catalyzed by malate dehydrogenase ... 

Water is added across the double bond of fumarate in a reaction which is catalyzed by the enzyme fumarase. The reaction is reversible, although slightly exer-gonic. At equilibrium there is 82% immolate. In the ninth and last step of the cycle, the secondary hydroxyl group of malate is dehydrogenated. The enzyme malate dehydrogenase transfers the hydrogen to NAD. The product of this reaction is oxaloacetate, the primer for the whole chain of reactions. The cycle is closed and we have finished one trip around it. 

In the third step, 1, -/3-hydroxyacyl-CoA is dehydrogenated to form /3-ketoacyl-CoA, by the action of /3-hydroxyacyl-CoA dehydrogenase NAD+ is the electron acceptor. This enzyme is absolutely specific for the l stereoisomer of hydroxyacyl-CoA The NADH formed in the reaction donates its electrons to NADH dehydrogenase, an electron carrier of the respiratory chain, and ATP is formed from ADP as the electrons pass to 02. The reaction catalyzed by /3-hydroxyacyl-CoA dehydrogenase is closely analogous to the malate dehydrogenase reaction of the citric acid cycle (p. XXX). 

Linked oxidation and decarboxylation. Metabolic pathways often make use of oxidation of a (3-hydroxy acid to a (3-oxoacid followed by decarboxylation in the active site of the same enzyme. An example is conversion of L-malate to pyruvate (Eq. 13-45). The Mg2+ or Mn2+-dependent decarboxylating malic dehydrogenase that catalyzes the reaction is usually called the malic enzyme. It is found in most organisms.237-240 While a concerted decarboxylation and dehydrogenation may sometimes occur,241-242 the enzymes of this group appear usually to operate with bound oxoacid intermediates as in Eq. 13-45. 

Some enzymes contain bound NAD+ which oxidizes a substrate alcohol to facilitate a reaction step and is then regenerated. For example, the malolactic enzyme found in some lactic acid bacteria and also in Ascaris decarboxylates L-malate to lactate (Eq. 15-12). This reaction is similar to those of isocitrate dehydrogenase,110-112 6-phosphogluconate dehydrogenase,113 and the malic enzyme (Eq. 13-45)114 which utilize free NAD+ to first dehydrogenate the substrate to a bound oxoacid whose (3 carbonyl group facilitates decarboxylation. Likewise, the bound NAD+ of the malolactic... 

The ratio [NAD+]/[NADH] appears to be maintained at a relatively constant value and in equilibrium with a series of different reduced and oxidized substrate pairs. Thus, it was observed that in the cytoplasm of rat liver cells, the dehydrogenations catalyzed by lactate dehydrogenase, sn-glycerol 3-phosphate dehydrogenase, and malate dehydrogenase are all at equilibrium with the same ratio of [NAD+]/[NADH].166 In one experiment rat livers were removed and frozen in less than 8 s by "freeze-clamping" (Section L,2) and the concentrations of different components of the cytoplasm determined167 the ratio [NAD+] / [NADH] was found to be 634, while the ratio of [lactate]/[pyruvate] was 14.2. From these values an... 

P-Decarboxylating dehydrogenases are a family of bifunctional enzymes that catalyze the Mg2+- and NAD(P)+-dependent dehydrogenation at C2, followed by their Mg2+-dependent decarboxylation at C3 of P-substituted malate ... 

Formation of Oxaloacetate in a Mitochondrion In the last reaction of the citric acid cycle, malate is dehydrogenated to regenerate the oxaloacetate necessary for the entry of acetyl-CoA into the cycle ... 

In the presence of oxygen and the cytochrome system, succinate is finally transformed to fumarate by a dehydrogenation process, and in turn, fumarate is converted into malate, which itself is dehydrogenated to form oxaloacetate. 

Succinyl-CoA is hydrolyzed (succinate-CoA Ugase, EC 6.2.1.4) to succinate, which then undergoes dehydrogenation (involving the conversion of ubiquinone to ubiquinol, succinate dehydrogenase, EC 1.3.5.1) to fumarate in a process that involves the loss of one pro-R and one pro-S hydrogen. Fumarate is then hydrated (fumarate hydratase, EC 4.2.1.2) to malate. The addition of water occurs stereospecificaUy to yield only S-malate. On the adjacent carbon, the pro-R hydro-... 

In the next step nature shows us a trick which is to be found time and again water is first added across a double bond and then hydrogen is abstracted from the addition product. In the present case fumarate hy-dratase catalyzes the addition of water to the double bond of fumarate to give malate which is then dehydrogenated to oxalacetate by malate dehydrogenase. NAD" " serves as the hydrogen acceptor. 

The mechanism of ll hydroxylation has been examined by tracer techniques using both deuterium and oxygeu-18. No deuterium is introduced into the product when the hydroxylation (of 11-deoxy-cortisol) is carried out in D2O (335). This observation rules out mechanisms of hydroxylation in which dehydrogenation is followed by hydration, as in the prototype succinate-fumarate-malate. In confirmation of this, A -unsatiuated analogues of deoxycorticosterone are not hydroxylated by mitochondrial preparations (335). When enzymic hydroxylation is carried out in media enriched with 0 , it is found that the oxygen of the 1 l-hydroxysteroids is derived from molecular oxygen (336,724) (Table XIV). The same results have been obtained in hydroxylations carried out by microorganisms (Table XV) (72,337). 

Aspartic Acid, as we have seen, not only can transfer its amino group to keto acids but also can supply one nitrogen directly to the urea cycle. In the second process, there arise succinoarginine and fumarate, which becomes malate by the addition of one water molecule. Malate, in turn, is dehydrogenated to oxaloacetate. The latter is also the product of the transamination of aspartate. 

Oxaloacetate can be regenerated from both cleavage products of isocitrate From glyoxylate by condensation with acetyl-CoA to form malate which is subsequently dehydrogenated, and from succinate through the usual citrate cycle. As a net result, 2 moles of activated acetate have been converted to succinate which can undergo further reactions by familiar pathwa3rs. Other synthetic pathways branch of these secondary products. 

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