Malate keto-acid

Fig. 42.9. Metabolism of the carbon skeletons of BCAA in skeletal muscle. 1. The first step in the metabolism of BCAA is transamination (TA). 2. Carbon from valine and isoleucine enters the TCA cycle as succinyl CoA and is converted to pyruvate by decarboxylating malate dehydrogenase (malic enzyme). 3. The oxidative pathways generate NADH and FAD(2H) even before the carbon skeleton enters the TCA cycle. The rate-limiting enzyme in the oxidative pathways is the a-keto acid dehydrogenase complex. The carbon skeleton also can be converted to glutamate and alanine, shown in blue.

Water is added across the double bond in the next step, catalyzed by fumarase, to give malic acid, or malate. Finally, malate dehydrogenase removes the two hydrogens from the hydroxyl carbon to regenerate the alpha-keto acid, oxaloacetate ... 

The transamination of the a-amino group to a keto acid acceptor (reaction 2) has been demonstrated in a number of higher plant studies (Nahler and Ruis, 1973 Streeter, 1977 Lloyd and Joy, 1978). The product of the transamination is 2-oxosuccinamate. This can be deamidated to oxaloacetate by lettuce and spinach leaf preparations (Meister, 1953). A similar reaction was reported by Streeter (1977) in soybean and pea leaf extracts. On the other hand, Joy (1978) reported that the 2-oxosuccinamate is reduced to 2-hydroxysuccinamate in these leaves in vivo. The apparent discrepancy between the results of Streeter (1977) and those of Joy (1978) may be due to the enzyme assay used by the former. It consisted of the oxidation of NADH in the presence of the enzyme extract and 2-oxosuccinamate. The assumption was that deamidation occurred leading to oxaloacetate which then acted as the substrate of endogenous malate dehydrogenase. The work of Davies (1961) showed that plant malate dehydrogenase is not specific for oxaloacetate, and it is possible that the 2-oxosuccinamate may act as a substrate. Meister (1953). actually measured the production of ammonia from 2-oxosuccinamate by his leaf preparations. 

Hence, those enzymes involving PEP carboxylation and regeneration, and malate production and degradation plus synthesis of the amino acids aspartate and alanine from the keto acids oxalacetate and pyruvate are deemed most interesting for our understanding in CAM. 

Because the NAD-malate dehydrogenases are such powerful catalysts, substrate level regulation is not likely. It is more reasonable to assume that it keeps the unstable, metabolically active keto acid (oxalacetate) in the stable form of malate. 

Pathways 8-10 are all thermodynamically favorable and produce 1 mol of ATP. Malonyl-CoA and malonic-semialdehyde can be derived from oxaloacetate by employing novel enzymes, with CoA-dependent oxaloacetate dehydrogenase and 2-keto acid decarboxylase activity, respectively. Malate can be converted to 3-HP using a novel enzyme with malate decarboxylase activity (Figure 14.4). These enzymes do not exist in nature and, because of this, it has been proposed that malate decarboxylase activity can be created by enzyme engineering in order to increase their specificity toward oxaloacetate and ability to produce the metabolic intermediates [33]. 

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 is an intermediate of many metabolic pathways. It also plays a role in the malate-aspartate shuttle, which transfers high energy electrons into mitochondria. Citrate is formed by the condensation of oxaloacetate with acetyl CoA. A transamination reaction transfers an amino group from an amino acid to an a-keto acid. Transfer of the amino group from aspartate to a-ketoglutarate forms oxaloacetate and glutamate. In gluconeogenesis, pyruvate is carboxylated in mitochondria to form oxaloacetate. After transfer to the cytosol, the enzyme phosphoenolpyruvate carboxykinase catalyses the conversion of oxaloacetate to phosphoenolpyruvate. 

A study of the photochemical reactivity of salts of the amino ketone (44) with enantiomerically pure carboxylates has been reported. The irradiations involved the crystalline materials using A, > 290 nm and the reactions are fairly selective which is proposed to be the result of hindered motion within the crystalline environment. Some of the many results, using (S)-(—)-malic acid, R-(+)-malic acid and (2R,3R)-(+)-tartaric acid, are shown in Scheme 1. The principal reaction in all of the examples is a Norrish Type II hydrogen abstraction and the formation of a 1,4-biradical. This leads mainly to the cis-cyclobutanol (45) by bond formation or the keto alkene (46) by fission within the biradical. A very minor path for the malate example is cyclization to the trn 5-cyclobutanol (47). A detailed examination of the photochemical behaviour of a series of large ring diketones (48) has been carried out. Irradiation in both the solid phase and solution were compared. Norrish Type II reactivity dominates and affords two cyclobutanols (49), (50) and a ring-opened product (51) via the conventional 1,4-biradical. Only the diketone (48a) is unreactive... 

The relative and absolute configuration of 35,125-dihydroxypalmitic acid, a constituent of the Ipomea operculata M. resin, was confirmed by synthesis starting with dimethyl L-malate (35). An efficient synfliesis of (55)-hydroxy-20 4(6 ,8Z,l 1Z,14Z) was accomplished by the coupling of two readily accessible synthons, methyl (55)-hydroxy-7-iodo-heptanoate and 4Z,7Z- tridecadien-l-yne (36). A highly stereoselective synthesis of P-dimorphecolic acid, (95)-hydroxy-18 2(10.E,12 ), has been reported the synthesis features a diastereoselective reduction of a keto intermediate [4] in which the tricarbonyliron lactone tether induces a 1,5-transfer of chirality followed by a stereoselective decarboxylation to create all of the stereochemical ele-... 

The absolute configuration of eldanolide, the pheromone from the wing glands of the male African sugar-cane borer, has been determined by a chiral synthesis of both of its enantiomers. (-t-)-Pantolactone (141) has been synthesized (in 40% yield) by a short sequence from (—)-(5 )-dimethyl malate. 1,2-0-Isopropyl-idene-D-glyceraldehyde is a useful chiral starting material for the synthesis of butyrolactones such as (142). The keto-lactone (143) is a useful intermediate in the synthesis of (+)-D-pantothenic acid it is prepared from readily available starting materials. ... 

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