P-Aminoisobutyrate

RS- P-Aminoisobutyric acid (a-methyl-P-alanine) [10569-72-9] M 103.1, m 176-178 , 178-180 , 181-182 , R -(-)- isomer [144-90-1] m 183 , [a] -21 (c 0.43, HjO), pKes,(,) 3.7, pKEst(2) 10.2. Colorless prisms from hot H O, were powdered and dried in vacuo. The purity is checked by paper chromatography (Whatman 1) using ninhydrin spray to visualise the amino acid Rp values in 95% MeOH and n-PrOH/5N HCOOH (8 2) are 0.36 and 0.50 respectively. [Kupiecki and Coon Biochem Prep 7 20 7960 Pollack J Am Chem Soc 65 1335 7943.] The R-enantiomer, isolated from iris bulbs or human urine was crystd from H2O and sublimed in vacuo [Asen et al. J Biol Chem 234 343 7959]. The RS-hydrochloride was recrystd from EtOH/Et20 m 128-129 , 130° [Bbhme et al. Chem Ber92 1258, 1260, 1261 7959]. 

P-aminoisobutyrate are elevated in the rare metabohc disorder hyperbeta-alaninemia. 

Unlike the end products of purine catabolism, those of pyrimidine catabolism are highly water-soluble COj, NH3, P-alanine, and P-aminoisobutyrate (Figure 34-9). Excretion of P-aminoisobutyrate increases in leukemia and severe x-ray radiation exposure due to increased destruction of DNA. However, many persons of Chinese or Japanese ancestry routinely excrete P-aminoisobutyrate. Humans probably transaminate P-aminoisobutyrate to methylmalonate semialdehyde, which then forms succinyl-CoA (Figure 19-2). 

These bases are then degraded to two P-amino acids, uracil to P-alanine and thymine to P-aminoisobutyrate. 

C2. Calchi-Novati, C., Ceppellini, R., Biancho, I., Silvestroni, E., and Harris, H., p-aminoisobutyric acid excretion in urine. A family study in an Italian population. Ann. Eugenics 18, 335-336 (1954). 

D5. de Groucny, J., and Eldon-Sutton, H., Genetic study of P-aminoisobutyric acid excretion. Am. J. Human Genet. 9, 76-80 (1957). 

Enzymatic synthesis of 3H-labelled P-ureidoisobutyric acid and P-aminoisobutyric acid from pHJthymidine... 

P-aminoisobutyric acid 59.3 pCi, p-ureidoisobutyric acid 18.8 pCi, radiochemical purity > 99% radiochemical purity > 99%... 

Nucleosides are metabolites of ribonucleic acid (RNA). As a result of excessive turnover of RNA, which occurs in such pathological conditions as cancer, inflammation, and AIDS, nucleosides are excreted into urine in increased amounts. Normal nucleosides (adenosine, guanosine, cytidine, uridine) either undergo further degradation into uric acid, p-alanine, or p-aminoisobutyrate or are reutilized. On the other hand, modified nucleosides, especially methylated nucleosides, are excreted unchanged in urine. Therefore, it seems that elevated levels of modified nucleosides could be an indicator of the presence of cancer and used as a diagnostic tool in cancer prognosis [23]. 

Metabolism Uracil is degraded to P-alanine and Thymine to P-aminoisobutyrate. 

Cells have free amino acid concentrations about 10 times those of plasma. The mechanisms maintaining this tenfold P-aminoisobutyric acid is seen. The mechanisms maintaining the gradient are unknown but may involve the membrane enzyme y-glutamyl transferase. 

The degradation of thymine yields P-aminoisobutyrate, as shown in the figure below, which can be converted to succinyl Co A and then degraded in the citric acid cycle. What cofactors are needed to convert P-aminoisobutyrate to succinyl CoA ... 

The transamination of P-aminoisobutyrate to form methylmalonate semialdehyde requires pyridoxal phosphate as a cofactor. This reaction is similar to the conversion of ornithine to glutamate y-semialdehyde. Then NAD+ serves as an electron acceptor for the oxidation of methylmalonate semialdehyde to methylmalonate. The conversion of methylmalonate to methylmalonyl CoA requires coenzyme A. The final reaction, in which methylmalonyl CoA is converted to succinyl CoA, is catalyzed by methylmalonyl CoA mutase, an enzyme that contains a derivative of vitamin B12 as its coenzyme. 

Reductive P. d. (Fig.). To a certain extent, this process represents a reversal of Pyrimidine biosynthesis (see). The pyrimidine ring is partially hydrogenated, and the resulting dihydro-compound is cleaved hydrolytically. Cytosine is converted to uracil by deamination, and uracil is degraded to p-alanine. Thymine is degraded to P-aminoisobutyrate. These end-products are transaminated and metabolized to common metabolic intermediates (Fig.). 

Some amino acid analogues such as a-[met/zy/- C]methylphenylalanine and a-[ C-methyl]methyltyrosine have been synthesized by alkylations of malonic esters (Gee and Langstrom 1991) as well as a-[met/zy/- C]methyltryptophan (Bourne et al. 1991 Pulak et al. 1996). a-aminoisobutyric acid, labeled in either the carboxylic position (Dunzendorfer et al. 1981) or 2-position (Prenant et al. 1995a), or the 3-position (Oberdorfer et al. 1993 Schmall et al. 1996) and P-aminoisobutyric acid (Alauddin et al. 1997) are other examples. Other... 

Kakimoto, Y., a. Kanazawa, T. Nakajima, and I. Sano Isolation of y-L-glutamyl-L-p-aminoisobutyric acid from bovine brain. Biochem. Biophys. Acta 100, 426 (1965). Kanamori, T., and H. Matsumoto Glutamine synthetase from rice plant roots. Arch. Biochem. Biophys. 125, 404 (1972). 

Morris, C. J., J. F. Thompson, S. Asen, and F. Irreverre The isolation of y-L-glutamyl-p-aminoisobutyric acid from Iris bulbs. J. Biol. Chem. 236, 1181 (1961). 

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