Mammalian folylpoly-. gamma. -glutamate synthetase. 4. In vitro and in vivo metabolism of folates and analogues and regulation of folate homeostasis
The regulation of folate and folate analogue metabolism was studied in vitro by using purified hog liver folylpolyglutamate synthetase as a model system and in vivo in cultured mammalian cells. The types of folylpolyglutamates that accumulate in vivo in hog liver, and changes in cellular folate levels and folylpolyglutamate distributions caused by physiological and nutritional factors such as changes in growth rates and methionine, folate, and vitamin B/sub 12/ status, can be mimicked in vitro by using purified enzyme. (/sup 3/H)Folylpolyglutamate distributions can be explained solely in terms of the substrate specificity of folylpolyglutamate synthetase and can be modeled by using kinetic parameters obtained with purified enzyme. Low levels of folylpolyglutamate synthetase activity are normally required for the cellular metabolism of folates to retainable polyglutamate forms, and consequently folate retention and concentration, while higher levels of activity are required for the synthesis of the long chain length derivatives that are found in mammalian tissues. The synthesis of very long chain derivatives, which requires tetrahydrofolate polyglutamates as substrates, is a very slow process in vivo. The slow metabolism of 5-methyltetrahydrofolate to retainable polyglutamate forms causes the decreased tissue retention of folate in B/sub 12/ deficiency. Although cellular folylpolyglutamate distributions change in response to nutritional and physiological modulations, it is unlikely that these changes play a regulatory role in one-carbon metabolism as folate distributions respond only slowly.
- Research Organization:
- Johns Hopkins Univ., Baltimore, MD
- OSTI ID:
- 6528478
- Journal Information:
- Biochemistry; (United States), Vol. 26:2
- Country of Publication:
- United States
- Language:
- English
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Mammalian folylpoly-. gamma. -glutamate synthetase. 2. Substrate specificity and kinetic properties
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FOLIC ACID
METABOLISM
SUBCELLULAR DISTRIBUTION
LIGASES
BIOCHEMISTRY
TRITIUM COMPOUNDS
CARBON 14 COMPOUNDS
CHO CELLS
GLUTAMIC ACID
HELA CELLS
IN VITRO
IN VIVO
LIQUID COLUMN CHROMATOGRAPHY
LIVER
SWINE
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BODY
CARBOXYLIC ACIDS
CHEMISTRY
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DISTRIBUTION
DOMESTIC ANIMALS
DRUGS
ENZYMES
GLANDS
HEMATINICS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PTERIDINES
SEPARATION PROCESSES
VERTEBRATES
VITAMIN B GROUP
VITAMINS
550201* - Biochemistry- Tracer Techniques