Maple Decarboxylase

In the case of hyperphenylalaninaemia, which occurs ia phenylketonuria because of a congenital absence of phenylalanine hydroxylase, the observed phenylalanine inhibition of proteia synthesis may result from competition between T.-phenylalanine and L-methionine for methionyl-/RNA. Patients sufferiag from maple symp urine disease, an inborn lack of branched chain oxo acid decarboxylase, are mentally retarded unless the condition is treated early enough. It is possible that the high level of branched-chain amino acids inhibits uptake of L-tryptophan and L-tyrosiae iato the brain. Brain iajury of mice within ten days after thek bkth was reported as a result of hypodermic kijections of monosodium glutamate (MSG) (0.5—4 g/kg). However, the FDA concluded that MSG is a safe kigredient, because mice are bom with underdeveloped brains regardless of MSG kijections (106). 

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

CWC Hu, KS Lau, TA Griffin, JL Chuang, CW Fisher, RP Cox, DT Chuang. Isolation and sequencing of a cDNA encoding the decarboxylase (El)-a precursor of bovine branched-chain a-keto acid dehydrogenase complex expression of El-a mRNA and subunit in maple-syrup-urine-disease and 3T3-L1 cells. J Biol Chem... 

Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease The third oxo-add dehydrogenase catalyzes the oxidative decarboxylation of the branched-chain oxo-acids that arise from the transamination of the branched-chain amino acids, leucine, isoleuctne, emd vtdine. It has a similEU subunit composition to pyruvate and 2-oxoglutarate dehydrogenases, and the E3 subunit (dihydrolipoyl dehydrogenase) is the stune protein as in the other two multienzyme complexes. Genetic lack of this enzyme causes maple syrup urine disease, so-called because the bremched-chain oxo-acids that are excreted in the urine have a smell reminiscent of maple syrup. 

Wynn RM, Davie JR, Chuang JL, Cote CD, Chuang DT. Impaired assembly of El decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type lA maple syrup urine disease. J Biol Chem 1998 273 13110-8. 

Branched-chain Branched-chain a-keto-ketoaciduria or acid decarboxylase maple syrup urine (leukocytes) i (recessive)... 

Maple syrup urine disease amino acid decarboxylase... 

Several metabolic blocks could account for the biochemical distortion observed in maple syrup disease. A deficiency in amino oxidase could lead to accumulation of amino acids. Because the enzyme has such a broad specificity, whenever it is completely deleted a more complex aminoaciduria can be expected to develop. The deletion of a specific transaminase could hardly explain the keto acid accumulation. Therefore, it seems more likely that the metabolic block involves a step between the keto acid and the simple acids, possibly the oxidative decarboxylation of the keto acid. This reaction requires coenzyme A, NAD, lipoic acid, and thiamine pyrophosphate, and it was described in some detail in the chapter devoted to the bioenergetic pathways. Leukocytes of at least some patients with maple syrup disease have been shown to contain normal transaminase activity but are defective in the oxidative decarboxylase. 

Multiple deletion cannot be excluded as a possible cause of maple syrup urine disease because a deficiency in a specific decarboxylase does not adequately explain the accumulation of indole derivatives and methionine. Of course, the branched amino acids or the corresponding keto acids could inhibit other metabolic pathways. 

A branched-chain amino acid found in elevated amounts in the blood along with valine and isoleucine in the inborn error of metabolism, maple syrup urine disease. This is due to a deficiency of branched-chain oxoacid decarboxylase, an enzyme involved in the degradation of the branched-chain amino acids. 

Figure 6.2. Metabolism of leucine, isoleucine and valine. The metabolic block in hypervalinaemia is marked A , that in maple syrup urine disease At least two different decarboxylases are involved. (Courtesy Blackwell, Oxford.)...

Rudiger, H.W., Langenbeck, U., Schulze-Schencking, M., Goedde, H.W. and Schuchmann, L. (1972), Defective decarboxylase in branched chain keto acid oxidase multienzyme complex in classical type of Maple Syrup Urine Disease. Hum. Genet., 14, 257. 

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