Beta-Alanine is an amino acid that functions as a neurotransmitter, and also in the biosynthesis of the abundant dipeptides carnosine and anserine in brain and muscle. Regulation of beta-alanine concentrations appears to be important in humans since hyper beta-alaninemia is accompanied by infant death and hypo beta-alainemia by epileptic-like seizures. We have been studying beta-alanine synthase (EC 3.5.1.6) from rat liver (as a model for the human enzyme) and our preliminary studies show it to be an allosteric enzyme, regulated both by its substrate and by its product, beta-alanine. Our results are consistent with the interpretation that this enzyme, beta-alanine synthase, is the major step for the formation of beta-alanine. We intend to completely purify this enzyme from rat liver, and complete physical and kinetic studies to describe the parameters for the regulation of this enzyme under physiological conditions. Studies on the possible synthesis of beta-alanine from other sources will also determine whether the degradation of uracil is the only significant source of beta-alanine. Antibodies will be made to the pure rat enzyme, and used for developmental and comparative studies to measure the expansion of beta-alanine synthase in different tissues, and as a function of development in rat. Upon completion of studies with the rat enzyme, we will begin to isolate and characterize the human enzyme. With antibodies to the rat enzyme as a probe, we will also start work on cloning the human gene for beta-alanine synthase.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040626-02
Application #
3298374
Study Section
Biochemistry Study Section (BIO)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Matthews, M M; Liao, W; Kvalnes-Krick, K L et al. (1992) beta-Alanine synthase: purification and allosteric properties. Arch Biochem Biophys 293:254-63