Malonic semialdehyde metabolism

The final step in the metabolic degradation of uracil is the oxidation of malonic semialdehyde to give malonvl CoA. Propose a mechanism. 

The most obvious route of metabolism of propionyl-CoA is further (1 oxidation which leads to 3-hydroxypropionyl-CoA (Fig. 17-3, step a). This appears to be the major pathway in green plants.17 Continuation of the (1 oxidation via steps a-c of Fig. 17-3 produces the CoA derivative of malonic semialdehyde. The latter can, in turn, be oxidized to malonyl-CoA, a P-oxoacid which can be decarboxylated to acetyl-CoA. The necessary enzymes have been found in Clostridium kluyveri,70 but the pathway appears to be little used. 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

CaaD is part of a pathway that is responsible for the degradation of the nematocide 1,3-dichloropropene in the soil bacterium Pseudomonas pavonaceae 170 (Figure l(b)). Its metabolic function is to convert trans-l>-chloroacrylate into malonate semialdehyde (4 at 3 s, 1.2 x lO moH Is ), which is probably the... 

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]. 

Gibson KM, Lee CF, Bennett MJ, Holmes B, Nyhan WL (1993) Combined malonic, methylmalonic and ethylmalonic acid semialdehyde dehydrogenase deficiencies an inborn error of beta-alanine, L-valine and L-alloisoleucine metabolism J Inherit Metab Dis 16 563-567... 

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