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Enzyme
Compound
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Target Concepts:
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Query: EC:1.4.1.2 (
glutamate dehydrogenase
)
4,380
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Reaction of phenylglyoxal with
glutamate dehydrogenase
(EC 1.4.1.4), but not with glutamate synthase (EC 2.6.1.53), from Bacillus megaterium resulted in complete loss of enzyme activity. NADPH alone or together with 2-oxoglutarate provided substantial protection from inactivation by phenylglyoxal. Some 2mol of [14C]
Phenylglyoxal
was incorporated/mol of subunit of
glutamate dehydrogenase
. Addition of 1mM-NADPH decreased incorporation by 0.7mol. The Ki for phenylglyoxal was 6.7mM and Ks for competition with NADPH was 0.5mM. Complete inactivation of
glutamate dehydrogenase
by butane-2,3-dione was estimated by extrapolation to result from the loss of 3 of the 19 arginine residues/subunit. NADPH, but not NADH, provided almost complete protection against inactivation. Butane-2,3-dione had only a slight inactivating effect on glutamate synthase. The data suggest that an essential arginine residue may be involved in the binding of NADPH to
glutamate dehydrogenase
. The enzymes were inactivated by pyridoxal 5'-phosphate and this inactivation increased 3--4-fold in the borate buffer. NADPH completely prevented inactivation by pyridoxal 5'-phosphate.
...
PMID:Inactivation of glutamate dehydrogenase and glutamate synthase from Bacillus megaterium by phenylglyoxal, butane-2,3-dione and pyridoxal 5'-phosphate. 2 36
The purified
glutamate dehydrogenase
(
GDH
) from Sulfolobus solfataricus showed remarkable thermostability and retained 90-95% of the initial activity after incubation at -20 degrees C, 4 degrees C, and 25 degrees C for up to 6 months. Unlike mammalian GDHs, the activity of
GDH
from Sulfolobus solfataricus was not significantly affected by the presence of various allosteric effectors such as ADP, GTP, and leucine. Incubation of
GDH
with increasing concentration of o-phthalaldehyde resulted in a progressive decrease in enzyme activity, suggesting that the o-phthalaldehyde-modified lysine or cysteine is directly involved in catalysis. The inhibition was competitive with respect to both 2-oxoglutarate (Ki = 30 microM) and NADH (Ki = 100 microM), further supporting a possibility that the o-phthalaldehyde-modified residues may be directly involved at the catalytic site. The modification of
GDH
by the arginine-specific dicarbonyl reagent phenylglyoxal was also examined with the view that arginine residues might play a general role in the binding of coenzyme throughout the family of pyridine nucleotide-dependent dehydrogenases. The purified
GDH
was inactivated in a dose-dependent manner by phenylglyoxal. Either NADH or 2-oxoglutarate did not gave any protection against the inactivation caused by a phenylglyoxal. This result indicates that
GDH
saturated with NADH or 2-oxoglutarate is still open to attack by phenylglyoxal.
Phenylglyoxal
was an uncompetitive inhibitor (Ki = 5 microM) with respect to 2-oxoglutarate and a noncompetitive inhibitor (Ki = 6 microM) with respect to NADH. The above results suggests that the phenylglyoxal-modified arginine residues are not located at the catalytic site and the inactivation of
GDH
by phenylglyoxal might be due to a steric hindrance or a conformational change affected by the interaction of the enzyme with its inhibitor.
...
PMID:Regulatory properties of glutamate dehydrogenase from Sulfolobus solfataricus. 1077 43
