Mammalian folylpoly-. gamma. -glutamate synthetase. 4. In vitro and in vivo metabolism of folates and analogues and regulation of folate homeostasis

Journal Article · Tue Jan 27 04:00:00 EST 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00376a027· OSTI ID:6528478

Cook, J D; Cichowicz, D J; George, S; Lawler, Ann; Shane, B

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), Journal Name: Biochemistry; (United States) Vol. 26:2; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BIOCHEMISTRY
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMISTRY
CHO CELLS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DISTRIBUTION
DOMESTIC ANIMALS
DRUGS
ENZYMES
FOLIC ACID
GLANDS
GLUTAMIC ACID
HELA CELLS
HEMATINICS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
LABELLED COMPOUNDS
LIGASES
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PTERIDINES
SEPARATION PROCESSES
SUBCELLULAR DISTRIBUTION
SWINE
TRITIUM COMPOUNDS
VERTEBRATES
VITAMIN B GROUP
VITAMINS