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2,3-diphosphoglycerate phosphatase activity of phosphoglycerate mutase: stimulation by vanadate and phosphate

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00379a010· OSTI ID:6219898
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The binding of inorganic vanadate (V/sub i/) to rabbit muscle phosphoglycerate mutase (PGM), studied by using /sup 51/V nuclear magnetic resonance spectroscopy, shows a sigmoidal dependence on vanadate concentration with a stoichiometry of four vanadium atoms per PGM molecule at saturating (V/sub i/). The data are consistent with binding of one divanadate ion to each of the two subunits of PGM in a noncooperative manner with an intrinsic dissociation constant of 4 x 10/sup -6/ M. The relevance of this result to other studies which have shown that the V/sub i/-stimulated 2,3-diphosphoglycerate (2,3-DPG) phosphatase activity of PGM has a sigmoidal dependence on (V/sub i/) with a Hill coefficient of 2.0 is discussed. At pH 7.0, inorganic phosphate has little effect on the 2,3-DPG phosphatase activity of PGM, even at concentrations as high as 50 mM. Similarly, 25 ..mu..M V/sub i/ has little effect on the phosphatase activity. However, in the presence of 25 ..mu..M V/sub i/, a phosphate concentration of 20 mM increases the phosphatase activity by more than 3-fold. This behavior is rationalized in terms of activation of the phosphatase activity by a phosphate/vanadate mixed anhydride. This interpretation is supported by the observation of strong activation of the phosphatase activity by inorganic pyrophosphate. A molecular mechanism for the observed effects of vanadate is proposed, and the relevance of this study to the possible use of vanadate as a therapeutic agent for the treatment of sickle cell anemia is discussed.
Research Organization:
Simon Fraser Univ., Burnaby, British Columbia
OSTI ID:
6219898
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:5; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
CHEMISTRY
ENZYME ACTIVITY
ENZYMES
ESTERASES
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPES
KINETICS
MAGNETIC RESONANCE
MAMMALS
MUSCLES
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
OXYGEN COMPOUNDS
PHOSPHATASES
PHOSPHATES
PHOSPHORUS COMPOUNDS
RABBITS
REACTION KINETICS
RESONANCE
STABLE ISOTOPES
STOICHIOMETRY
TRANSITION ELEMENT COMPOUNDS
VANADATES
VANADIUM 51
VANADIUM COMPOUNDS
VANADIUM ISOTOPES
VERTEBRATES