Acids a-ketoacids

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... 

Amino acidt + a-ketoacid2 amino acid + a-ketoacid ... 

Amino acid a-ketoacid Aldehyde Higher alcohol... 

The initial step in the metabolism of amino acids is the removal of the amino group (-NH ), leaving the carbon skeleton of the amino acid. Chemically, these carbon skeletons are ketoacids (more correctly, they are oxo-acids). A ketoacid has a —C=0 group in place of the HC-NH group of an amino acid the metabolism of ketoacids is discussed in section 9.3.2. 

As shown in equation 12, the chemistry of this developer s oxidation and decomposition has been found to be less simple than first envisioned. One oxidation product, tetramethyl succinic acid (18), is not found under normal circumstances. Instead, the products are the a-hydroxyacid (20) and the a-ketoacid (22). When silver bromide is the oxidant, only the two-electron oxidation and hydrolysis occur to give (20). When silver chloride is the oxidant, a four-electron oxidation can occur to give (22). In model experiments the hydroxyacid was not converted to the keto acid. Therefore, it seemed that the two-electron intermediate triketone hydrate (19) in the presence of a stronger oxidant would reduce more silver, possibly involving a species such as (21) as a likely reactive intermediate. This mechanism was verified experimentally, using a controlled, constant electrochemical potential. At potentials like that of silver chloride, four electrons were used at lower potentials only two were used (104). 

The preparation of long-chain fatty acids has been carried out in this way because cleavage of 115 with strong sodium hydroxide gives the ketoacid (116), which is easily reduced by the Wolf-Kishner method to the saturated acid. A similar sequence of reactions can be carried out starting with the cyclopentanone enamine, and this method allows lengthening the chain... 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Figure A8.18 A racemic mixture of a-hydroxyacids (like L, D-lactate) can be transformed via the corresponding a-ketoacid (pyruvate) to the desired L-amino acid (L-alanine) with cofactor recycling.

It should be noted that the absence of a proton in the a position in the case of N-Br-aminoisobutyric acid makes unoperative its decomposition to form an a-ketoacid, and the slight increase in the observed reaction rate constant upon increasing the NaOH concentration can be attributed to a secondary decomposition process, probably leading to the formation of an hydrazine (refs. 22 - 24). 

A number of factors complicate the aerobic metabolism of amino acids—different enzymes may be used even for the same amino acid the enzymes may be inducible or constitutive depending on their function a-ketoacids may be produced by deamination or amines by decarboxylation. 

Another model is based on the fact that the genetic code shows a number of regularities, some of which have already been mentioned above. It is suspected that codons beginning with C, A or U code for amino acids which were formed from a-ketoacids (or a-ketoglutarate, 1-KG), oxalacetate (OAA) and pyruvate. This new model, which is quite different from the previous models, assumes that a covalent complex formed from two nucleotides acted as a catalyst for chemical reactions such as the reductive amination of a-ketoacids, pyruvate and OAA. More recent analyses suggest that the rTCA cycle (see Sect. 7.3) could have served as a source of simple a-ketoacids, including glyoxylate, pyruvate, OAA and a-KG. a-Ketoacids could, however, also have been formed via a reductive acetyl-CoA reaction pathway. The bases of the two nucleotides specify the amino acid synthesized and were retained until the modern three-letter codes were established (Copley et al., 2005). 

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

It is appropriate here to look at the structure of oxaloacetic acid, a critical intermediate in the Krebs cycle, and to discover that it too is a P-ketoacid. In contrast to oxalosuccinic acid, it does not suffer decarboxylation in this enzyme-mediated cycle, but is used as the electrophile for an aldol reaction with acetyl-CoA (see Box 10.4). 

An acyl-transfer and redox coenzyme containing two sulfhydryl groups that form a dithiolane ring in the oxidized (disulfide) form. The redox potential at pH 7 is -0.29 volts. Lipoic acid is attached to the e-amino group of lysyl residues of transacetylases (subunit of a-ketoacid dehydrogenase complexes), thereby permitting acyl... 

Paxton, R. Harris, R.A. Clofibric acid, phenylpyruvate, and dichloroacetate inhibition of branched-chain a-ketoacid dehydrogenase kinase in vitro and in perfused rat heart. Arch. Biochem. Biophys., 231, 58-66 (1984)... 

D-Amino acid oxidase D-Amino acids (see p. 5) are found in plants and in the cell walls of microorganisms, but are not used in the synthesis of mammalian proteins. D-Amino acids are, hew ever, present in the diet, and are efficiently metabolized by 1he liver. D-Amino acid oxidase is an FAD-dependent enzyme that catalyzes the oxidative deamination of these amino acid isomers. The resulting a-ketoacids can enter the general pathways of amino acid metabolism, and be reaminated to L-isomers, or cafe balized for energy. 

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. 

Maple syrup urine disease (MSUD) is a recessive disorder in which there is a partial or complete deficiency in branched-chain a-ketoacid dehydrogenase—an enzyme that decarboxylates leucine, isoleucine, and valine. These amino acids and their corresponding a-keto acids accumulate in the blood, causing a toxic effect that interferes with brain func tion. Symptoms include feeding problems, vomiting, dehydration, severe metabolic acidosis, and a characteristic smell of the urine. If untreated, the disease leads to mental retardation, physical disabilities, and death. Diagnosis is based on a blood sample within 24 hours of birth. Treatment of MSUD involves a synthetic formula that contains limited amounts of leucine, isoleucine, and valine. 

Ketimine 121,744s. See also Schiff base from pyridoxal phosphate 742 as electron acceptor 746, 747 a-Ketoacid. See 2-Oxoacid Ketoamine 434s Ketodeoxyoctonate. See KDO Ketone(s), acidity of 46 Khorana, H. Gobind 84 Kidney cells, alkaline phosphatase in 645... 

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