Aluminum coordination chemistry and the inhibition of phosphoryl-transferring enzymes
Aluminium ion is a potent inhibitor of the enzymes hexokinase (K/sub i/ = 0.16 ..mu..M) and glycerokinase (K/sub i/ = 4.0 ..mu..M). It has been shown that aluminum forms a complex with ATP that is 80 times more stable than the magnesium complex with ATP which is the normal substrate for phosphoryl-transferring enzymes. Kinetic studies performed on several kinases at pH 7.0 have shown that Al-ATP is a competitive inhibitor vs. Mg-ATP with moderate K/sub i/ values (0.1-0.5 mM) for creatine kinase(CK) and myokinase(MK), and weakly competitive (K/sub i/ > 0.5 mM) with acetate, galactose, arginine and gluconate kinases. Equilibrium dialysis binding studies indicate no significant binding of aluminum ion by the enzymes, while the interaction of aluminum ion with ADP and ATP has been characterized by /sup 13/C, /sup 27/Al, and /sup 31/P NMR spectroscopy. It appears that the inhibition by aluminum is as the Al-nucleotide complex rather than direct binding of free aluminum ion by the enzyme. Kinetic studies indicate that Al/sup 3 +/ inhibition of CK and MK is pH dependent with decreased values of K/sub i/ at lower pH. At pH 6.1 K/sub i/ = 25 ..mu..M for MK (160 ..mu..M at pH 7.0) and 53 ..mu..M for CK (240 ..mu..M at pH 7.0). This may be due to an increased effective concentration of aluminum ion at lower pH.
- Research Organization:
- Univ. of Akron, OH
- OSTI ID:
- 5020593
- Report Number(s):
- CONF-8606151-; TRN: 86-034807
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ALUMINIUM
BIOLOGICAL EFFECTS
PHOSPHOTRANSFERASES
BIOCHEMICAL REACTION KINETICS
ADP
ALUMINIUM 27
ATP
CARBON 13
NMR SPECTRA
PH VALUE
PHOSPHORUS 31
ALUMINIUM ISOTOPES
CARBON ISOTOPES
ELEMENTS
ENZYMES
EVEN-ODD NUCLEI
ISOTOPES
KINETICS
LIGHT NUCLEI
METALS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
REACTION KINETICS
SPECTRA
STABLE ISOTOPES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques
550600 - Medicine