Abstract

This research project continues to elucidate the reaction mechanisms involved in the metabolism of L-lysine to delta1-piperideine-2-carboxylic acid (P2C), P2C to L-pipecolic acid, L-pipecolic acid to delta1- piperideine-6-carboxylic acid (P6C), P6C to L-alpha-amonoadipic acid (AAA), and AAA to alpha-ketoadipic acid. It will isolate, purify to homogeneity and characterize L-lysine oxidase, P2C reductase, pipecolate oxidase, L-alpha-aminoadipic delta-semialdehyde (or P6C) oxidoreductase, and alpha-aminoadipate:alpha-ketoglutarate aminotransferase in the brain. It will isolate, purify and compare the characteristics of pipecolate oxidase localized in the peroxisomes and mitochondria. Mono- and polyclonal antibodies against L-lysine oxidase, P2C reductase, pipecolate oxidase, P6C oxidoreductase and alpha-aminoadipate:alpha-kekoglutarate aminotransferase in the rat brain will be prepared. The regional distributions of L-lysine oxidase, P2C reductase, pipecolate oxidase, P6C oxidoreductase and alpha-aminoadipate:alpha-kekoglutarate aminotransferase in the rat brain through enzyme activity study and immunocytochemical study. It will examine the developmental aspects of enzymes in the L-lysine pathway through enzyme activity assays and immunocytochemical study. It will examine the effect of L-alpha- aminoadipic acid and other lysine metabolites on the purified kynurenine aminotransferase and in astrocyte cultures. It will study the uptake of L-AAA in the astrocytes through cell cultures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS011822-15A2
Application #
2262351
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1977-12-01
Project End
1996-11-30
Budget Start
1993-12-15
Budget End
1994-11-30
Support Year
15
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Chang, Y F; Cauley, R K; Chang, J D et al. (1997) L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and tissue culture. Neurochem Res 22:825-9
Tsai, M J; Chang, Y F; Schwarcz, R et al. (1996) Characterization of L-alpha-aminoadipic acid transport in cultured rat astrocytes. Brain Res 741:166-73
Chang, Y F; Gao, X M (1995) L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor. Neurochem Res 20:931-7
Chang, Y F; Charles, A K (1995) Uptake and metabolism of delta 1-piperidine-2-carboxylic acid by synaptosomes from rat cerebral cortex. Biochim Biophys Acta 1238:29-33
Chang, Y F; Wang, Y; Cauley, R K et al. (1993) Chronic L-lysine develops anti-pentylenetetrazol tolerance and reduces synaptic GABAergic sensitivity. Eur J Pharmacol 233:209-17
Rao, V V; Pan, X; Chang, Y F (1992) Developmental changes of L-lysine-ketoglutarate reductase in rat brain and liver. Comp Biochem Physiol B 103:221-4
Rao, V V; Chang, Y F (1992) Assay for L-pipecolate oxidase activity in human liver: detection of enzyme deficiency in hyperpipecolic acidaemia. Biochim Biophys Acta 1139:189-95
Chang, Y F; Gao, X M; Chen, J S (1991) Correlation between enhancement of [3H]flunitrazepam binding and suppression of pentylenetetrazol-induced seizures by L-lysine. Eur J Pharmacol 193:239-47
Chang, Y F; Ghosh, P; Rao, V V (1990) L-pipecolic acid metabolism in human liver: L-alpha-aminoadipate delta-semialdehyde oxidoreductase. Biochim Biophys Acta 1038:300-5
Rao, V V; Chang, Y F (1990) L-pipecolic acid metabolism in human liver: detection of L-pipecolate oxidase and identification of its reaction product. Biochim Biophys Acta 1038:295-9

Showing the most recent 10 out of 16 publications