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Regulation of the glycine cleavage system in rat liver

Thesis/Dissertation ·
OSTI ID:6108188
Catabolism of glycine, via the glycine cleavage system was investigated in isolated, fully functional, rat liver mitochondria, and the isolated perfused rat liver. Metabolic flux through the glycine cleavage system, which catalyzes the tetrahydrofolate-dependent cleavage of glycine yielding carbon dioxide, ammonia, N/sup 5/,N/sup 10/-methylenetetrahydrofolate, and NADH + H/sup +/, was monitored by measuring the production of /sup 14/CO/sub 2/ from (1-/sup 14/C)glycine. The glycine cleavage system was demonstrated to be responsible for nearly all /sup 14/CO/sub 2/ production from (1-/sup 14/C)glycine in both isolated mitochondria and the perfused rat liver. Glycine decarboxylation by rat liver mitochondria was highly sensitive to the metabolic state in which the mitochondria were maintained. Production of /sup 14/CO/sub 2/ from (1-/sup 14/C)glycine was stimulated in State 3 over State 4 and was maximal in the uncoupled state. Alternatively, respiratory inhibitors, such as rotenone, and reducing substrates, inhibited mitochondrial glycine decarboxylation strongly. Propionate stimulated glycine decarboxylation by rat liver mitochondria with a concomitant decrease in the measured intramitochondrial NADPH content. Incubation of mitochondria with propionate evoked a large decrease in the measured intramitochondrial ATP content and a large increase in AMP content. Manipulation of the intramitochondrial adenine nucleotide profile demonstrated that no direct correlation existed between rates of mitochondrial glycine decarboxylation and the intramitochondrial content of either ATP, ADP, or AMP.
Research Organization:
Texas Univ., San Antonio (USA). Health Science Center
OSTI ID:
6108188
Country of Publication:
United States
Language:
English