3- aminoisobutyrate

Le = leucine. Since the material for the Bulletin was prepared, it has become probable that the substance originally identified by Dent as methionine sulfoxide is actually (3-aminoisobutyric acid. Nature (London), 167, 307 (1951). Ale = average alcohol consumption by all rats in each strain expressed as ml. ethanol/100 g. rat/day. From Janet G. Reed, Univ. Texas Pub/., 5109, 146147... 

Unlike the purine rings, which are not cleaved in human cells, the pyrimidine ring can be opened and degraded to highly soluble struc tures, such as (3-alanine, and (3-aminoisobutyrate, which can serve as precursors 67 acetyl CoA and succinyl CoA, respectively. 

Thymine undergoes degradation in a pathway analogous to that of Eq. 25-18, but with the formation of 3-aminoisobutyrate. The latter can be oxidatively converted to methylmalonate (Eq. 25-19), which can enter the methylmalonyl pathways (Fig. 17-3). 

Enzymes present in mammalian liver are capable of the catabolism of both uracil and thymine. The first reduces uracil and thymine to the corresponding 5,6-dihydro derivatives. This hepatic enzyme uses NADPH as the reductant, whereas a similar bacterial enzyme is specific for NADH. Similar enzymes are apparently present in yeast and plants. Hydropyrimidine hydrase then opens the reduced pyrimidine ring, and finally the carbamoyl group is hydrolyzed off from the product to yield /3-alanine or /3-aminoisobutyric acid, respectively, from uracil and thymine (see fig. 23.23). 

In summary we underline the fact that as far as urine analysis is concerned, and this is also true for blood, the most satisfactory results published so far are those obtained with Moore and Stein s 1954 procedure (see (b) Dowex 50-X4 columns) whereas the two latest improvements in technique open the way to much wider investigation in this field of biochemical and medical research. The technique is also applicable for the determination of a single amino acid, adequate shortcuts and simplifications in the procedure being introduced accordingly. As examples, we shall mention that appropriate rapid operations have been described for the separation on ion exchange columns and subsequent determination of (3-alanine (C20), (3-aminoisobutyric acid (E5) or y-aminobutyric acid (W1). Similar adjustments may also be made for other amino acids, such as the basic amino acids, for instance, with Moore and Stein s 1954 procedure (M15). 

L8. Lindan, O., Paper chromatography of Gambian urines amino-acid pattern and excretion of 3-aminoisobutyric acid. Malnutrition in African mothers, infants and young children. Rep. 2nd Inter-african (C.C.T.A.) Conf. on Nutrition, Gambia, 1952 pp. 195-196 (1954). 

Amino acid excretion in urine varies with maturation of renal tubular function. Premature infants, especially during the first week, have a generalized physiological renal aminoaciduria (see Figure 20-2) even at full term, aminoaciduria is more pronounced than in normal adults. In the urine of normal adults, glycine is usually the dominant fraction, with alanine, serine, glutamine, and— in indulgent meat eaters— histidine and 1-methylhistidine present in smaller quantities. In some normal urine, taurine is prominent in others, (3-aminoisobutyric acid is seen. 

Alanine and /3-aminoisobutyrate are the nitrogenous waste products of pyrimidine base catabolism. 

Uracil and thymine are converted to their end products, /3-alanine and /3-aminoisobutyrate, respectively, in parallel pathways. In the first step, uracil and thymine are reduced by dihydrouracil dehydrogenase to their corresponding dihydro derivatives. As these latter molecules are hydrolyzed, the rings open, yielding /3-ureidopropionate and /3-ureidoisobutyrate, respectively. Finally, /3-alanine and /3-aminoisobutyrate are produced in deamination reactions catalyzed by /3-ureidopropionase. 

In several conditions, /3-aminoisobutyrate is produced in such large quantities that it appears in urine. Among these are a genetic predisposition for slow /3-aminoisobutyrate conversion to succinyl-CoA and diseases that cause massive cell destruction, such as leukemia. Because it is soluble, excess /3-aminoisobutyrate does not cause problems comparable to those observed in gout. 

Fig. 19. Michaelis-Menten constant f Al-acetyl-L-amino add methyl esters with a-chymotrypsin versus the effluent volume of the amino acid from a cation-exchange resin [72]. 1, glydne 2, alanine 3, aminoisobutyric acid 4, valine S, methionine 6, leucine 7, tyrosine 8, phenylalanine.

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

Quantitation of 3-Aminoisobutyric Acid in Urine by Mass Fragmentography... 

Examination of plasma and urine revealed elevated quantities of jff-ala-nine, 3-hydroxypropionic acid, (R)- and (S)-3-aminoisobutyric acid, (R)-and (S)-3-hydroxyisobutyric acid and (S)-2-hydroxymethylbutyric acid. Direct enzymatic assay of methylmalonate semialdehyde dehydrogenase is unavailable revealed homozygosity for DNA analysis 1336 G>A transversion which substituted an arginine for a highly conserved glycine at amino acid residue 446. 

Methylmalonate semialdehyde has been shown to be transaminated to form /3-aminoisobutyrate, as well as being decarboxylated to propionyl aldehyde (89). Previously it had been determined that this compound was formed in the metabolism of dihydroth3mine (98, 99). Kupiecki and Coon (89) prepared a transaminase from pig kidney which catalyzes the transamination of methylmalonate semialdehyde with glutamic acid as the amino group donor to /3-aminoisobutyric acid according to Eq. (6). 

Kupiecki and Coon 89) established that the transaminase which forms /3-aminoisobutyric acid also reversibly transaminates /3-alanine. The enzyme specifically requires a-ketoglutarate. From these results the authors suggest that valine is a precursor of /3-alanine in animal tissues. 

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