Abstract

We will continue our investigations on the structure, mechanism and biological functions of the three citrate enzymes, citrate lyase, citrate synthase and ATP-citrate lyase. In this proposal we intend to examine the structure of citrate synthase in situ in relation to the change in its inhibitory pattern from an ATP sensitive enzyme in vitro to an ATP insensitive one in vivo. We shall also attempt to determine if the genes for citrate lyase are carried by a plasmid and attempt to isolate and study these genes. Finally, we shall study the residues and surrounding peptides in ATP-citrate lyase that are responsible for the formation of a histidyl phosphate intermediate and the citryl enzyme intermediate in the overall reaction. We will study the properties of the recently purified rat brain ATP-citrate lyase. We will continue our efforts to relate the mechanisms and structures of the three citrate enzymes. In addition, we will use the information on enzyme structure and mechanism to gain insight into each enzymes biological role and the control of its activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK011313-19
Application #
3224773
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1977-01-01
Project End
1988-02-29
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
19
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Evans, C T; Kurz, L C; Remington, S J et al. (1996) Active site mutants of pig citrate synthase: effects of mutations on the enzyme catalytic and structural properties. Biochemistry 35:10661-72
Srere, P A; Sumegi, B (1994) Processivity and fatty acid oxidation. Biochem Soc Trans 22:446-50
Sandor, A; Johnson, J H; Srere, P A (1994) Cooperation between enzyme and transporter in the inner mitochondrial membrane of yeast. Requirement for mitochondrial citrate synthase for citrate and malate transport in Saccharomyces cerevisiae. J Biol Chem 269:29609-12
McGarry, J D (1994) Disordered metabolism in diabetes: have we underemphasized the fat component? J Cell Biochem 55 Suppl:29-38
Lindbladh, C; Brodeur, R D; Small, W C et al. (1994) Metabolic studies on Saccharomyces cerevisiae containing fused citrate synthase/malate dehydrogenase. Biochemistry 33:11684-91
Sumegi, B; Sherry, A D; Malloy, C R et al. (1993) Evidence for orientation-conserved transfer in the TCA cycle in Saccharomyces cerevisiae: 13C NMR studies. Biochemistry 32:12725-9
Srere, P A (1993) 17th Fritz Lipmann Lecture. Wanderings (wonderings) in metabolism. Biol Chem Hoppe Seyler 374:833-42
Srere, P A (1992) The molecular physiology of citrate. Curr Top Cell Regul 33:261-75
McGarry, J D (1992) What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258:766-70
Sumegi, B; McCammon, M T; Sherry, A D et al. (1992) Metabolism of [3-13C]pyruvate in TCA cycle mutants of yeast. Biochemistry 31:8720-5

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