Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes
- Cornell Univ., Ithaca, NY (USA)
To assess the extent to which low hepatic gamma-cystathionase levels affect methionine flux to cysteine in hepatocytes, the effect of inhibition of gamma-cystathionase activity with propargylglycine on the metabolism of L-({sup 35}S)methionine was determined in studies with freshly isolated rat hepatocytes. gamma-Cystathionase activity was inhibited 25%, 42%, 63% and 76% (maximal inhibition) by treatment with 2.5 mumol/L, 0.01 mmol/L, 0.02 mmol/L and 2 mmol/l propargylglycine, respectively. Inhibition of gamma-cystathionase activity with up to 0.02 mmol/L propargylglycine had no statistically significant effect on ({sup 35}S)glutathione, ({sup 35}S)sulfate or ({sup 35}S)cysteine formation from ({sup 35}S)methionine. However, treatment of cells with 2 mmol/L propargylglycine markedly inhibited the metabolism of ({sup 35}S)methionine to ({sup 35}S)glutathione by 93%, to ({sup 35}S)sulfate by 88% and to ({sup 35}S)cysteine by 89%; ({sup 35}S)cystathionine accumulation in these incubation systems was 60 times control. Hepatic gamma-cystathionase activity in premature infants has been reported to be about 23% of mature levels; this level of gamma-cystathionase activity may limit cysteine synthesis by the methionine transsulfuration pathway. No evidence for cysteine synthesis from serine and sulfide, which can be catalyzed by cystathionine beta-synthase, or for methionine metabolism by an S-adenosylmethionine-independent pathway was obtained.
- OSTI ID:
- 6532112
- Journal Information:
- Journal of Nutrition; (USA), Vol. 120:8; ISSN 0022-3166
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CYSTEINE
BIOSYNTHESIS
LYASES
ENZYME ACTIVITY
METHIONINE
METABOLISM
SULFATES
BIOLOGICAL PATHWAYS
GLUTATHIONE
GLYCINE
LIVER CELLS
SERINE
SULFUR 35
TAURINE
TRACER TECHNIQUES
AMINES
AMINO ACIDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
HYDROXY ACIDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
SOMATIC CELLS
SULFONIC ACIDS
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
THIOLS
550201* - Biochemistry- Tracer Techniques