Branched-chain ketoacids

Mac, M. and Nalecz, K. A. Expression of monocarboxylic acid transporters (MCT) in brain cells. Implication for branched chain alpha-ketoacids transport in neurons. Neurochem. Int. 43 305-309, 2003. 

Rare patients respond to the administration of thiamine in large doses (10-30mg/day). The clinical course is even more mild than that of patients with intermittent disease. Thiamine is a cofactor for the branched-chain ketoacid dehydrogenase, and the presumed mutation involves faulty binding of the apoprotein to this vitamin. 

Branched-chain ketoacid dehydrogenase (metabolism of branched-chain amino acids)... 

Branched-Chain Ketoacid Dehydrogenase Deficiency (Maple Syrup Urine Disease)... 

Maple syrup urine disease (branched-chain ketoacid dehydrogenase)... 

Answer C. Maple syrup urine disease substrates are branched chain a-ketoacids derived from the branched chain amino acids. 

The nickel oxide electrode is generally useful for the oxidation of alkanols in a basic electrolyte (Tables 8.3 and 8.4). Reactions are generally carrried out in an undivided cell at constant current and with a stainless steel cathode. Water-soluble primary alcohols give the carboxylic acid in good yields. Water insoluble alcohols are oxidised to the carboxylic acid as an emulsion. Short chain primary alcohols are effectively oxidised at room temperature whereas around 70 is required for the oxidation of long chain or branched chain primary alcohols. The oxidation of secondary alcohols to ketones is carried out in 50 % tert-butanol as solvent [59], y-Lactones, such as 10, can be oxidised to the ketoacid in aqueous sodium hydroxide [59]. 

Paxton, R. Harris, R.A. Isolation of rabbit liver branched chain a-ketoacid dehydrogenase and regulation by phosphorylation. J. Biol. Chem., 257, 14433-14439 (1982)... 

Shimomura, Y. Kuntz, M.J. Suzuki, M. Ozawa, T. Harris, R.A. Monovalent cations and inorganic phosphate alter branched-chain a-ketoacid dehydrogenase-kinase activity and inhibitor sensitivity. Arch. Biochem. Biophys., 266, 210-218 (1988)... 

Doering, C.B. Coursey, C. Spangler, W. Danner, D.J. Murine branched chain a-ketoacid dehydrogenase kinase cDNA cloning, tissue distribution, and temporal expression during embryonic development. Gene, 212, 213-219 (1998)... 

Nellis, M.M. Doering, C.B. Kasinski, A. Danner, D.J. Insulin increases branched-chain cr-ketoacid dehydrogenase kinase expression in Clone 9 rat cells. Am. J. Physiol., 283, E853-E860 (2002)... 

Popov, K.M. Zhao, Y Shimomura, Y. Jaskiewicz, J. Kedishvili, N.Y Irwin, J. Goodwin, G.W. Harris, R.A. Dietary control and tissue specific expression of branched-chain cr-ketoacid dehydrogenase kinase. Arch. Biochem. Biophys., 316, 148-154 (1995)... 

Maple syrup urine disease (MSUD) is a recessive disorder in which there is a partial or complete deficiency in branched-chain o-ketoacid dehydrogenase, an enzyme that decarboxylates leucine, isoleucine, and valine (see Figure 20.10). These amino acids and their corre sponding a-keto acids accumulate in the blood, causing a toxic effect that interferes with brain functions. The disease is characterized by feeding problems, vomiting, dehydration, severe metabolic acidosis, and a characteristic maple syrup odor to the urine. If untreated, the disease leads to mental retardation, physical disabilities, and death. 

Correct answer = B. Alkaptonuria is a rare metabolic disease involving a deficiency in homogentisic acid oxidase, and the subsequent accumulation of homogentisic acid in the urine, which turns dark upon standing. The elevation of methylmalonate (due to methylmalonyl CoA mutase deficiency), phenylpyruvate (due to phenylalanine hydroxlyase deficiency), a-ketoisovalerate (due to branched-chain a-ketoacid dehydrogenase deficiency), and homocystine (due to cystathionine synthase deficiency) are inconsistent with a healthy child with darkening of the urine. 

Branched-chain ketoacid dehydrogenase Phenylalanine hydroxylase Tyrosine hydroxylase... 

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

B Zhang, DW Crabb, RA Harris. Nucleotide and deduced amino acid sequence of the El-a subunit of human liver branched-chain a-ketoacid dehydrogenase. Gene... 

I Matsuda, J Asaka, I Akaboshi, F Endo, H Mitsubuchi, Y Nobukuni. Maple syrup urine disease complete primary structure of the El-(3 subunit of human branched chain a-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease. J Clin Invest 86 242-247, 1990. 

MC McKean, KA Winkeler, DJ Danner. Nucleotide sequence of the 5 end including the initiation codon of cDNA for the Ela subunit of the human branched chain a-ketoacid dehydrogenase complex. Biochim Biophys Acta 1171 109-112, 1992. 

Maple syrup urine 1 300,000 Branched-chain Branched-chain a-ketoacid... 

TDP-dependent enzymes include transketolase, an enzyme component of the pentose shunt pathway, pyruvate dehydrogenase complex, and aKGDH a tricarboxylic acid cycle enzyme (Fig. 3). Branched-chain ketoacid dehydrogenases are also TDP-dependent. 

Metabolic intermediates and other local" effectors Many target specific enzymes, such as pyruvate dehydrogenase kinase and branched-chain ketoacid dehydrogenase kinase ... 

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