OXIDATIVE MODIFICATION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE
OXIDATIVE MODIFICATION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE
批准号:
3857971
负责人:
L I SZWEDA
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
随着各种真核细胞的衰老,葡萄糖的比活性-
英文摘要
As a variety of eukaryotic cells age, the specific activity of glucose-
6-phosphate dehydrogenase (G-6-PDH) declines as much as 50%. Due to the
central role of this enzyme in metabolism, it is important to define
factors responsible for this loss in enzyme activity. One promising
possibility is that this may be due to oxidative modification, a process
which has recently been implicated in the age-related loss in activity of
a number of enzymes.
We have found that G-6-PDH from Leuconostoc mesenteroides is
rapidly inactivated by micromolar concentrations of ferrous iron and
hydrogen peroxide. Inactivation correlated with the formation of one
carbonyl functionality per enzyme subunit, indicating that inactivation is
the result of site-specific oxidative modification. Our results suggest
that ferrous iron binds to the glucose-6phosphate binding site and that
interaction of the enzyme-bound ferrous iron with hydrogen peroxide leads
to the oxidative modification of amino acids essential for enzyme activity.
Partially inactivated enzyme remained predominantly in the dimeric form and
no change in the apparent affinity of the remaining active subunits for
substrate was observed. Partial inactivation did, however, lead to a
decrease in the thermal stability of the remaining activity. This decrease
in thermal stability could be largely overcome by the addition of
glucose-6-phosphate. Thus, while exposure to hydrogen peroxide and ferrous
iron results in the irreversible inactivation of G-6-PDH, the resulting
modification is selective, leads to the formation of heterodimers of both
active and inactive subunits, and does not appear to cause large-scale
structural changes.
Our results demonstrate the inherent susceptibility of G-6-PDH
from L. mesenteroides to modification by an oxidation system known to exist
in vivo. An assessment of the physiological significance of ferrous
iron-catalyzed oxidation of G-6-PDH awaits extension of these studies to
mammalian sources known to accumulate less active or inactive forms of the
enzyme as a function of age.
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会议论文
MODIFICATION OF PROTEIN BY THE LIPID PEROXIDATION PRODUCT 4-HYDROXY-2-NONENAL
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批准号:3757583
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:L I SZWEDA
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依托单位:
AGE-RELATED INCREASE IN LIVER RETINYL PALMITATE--RELATIONSHIP TO LIPOFUSCIN
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批准号:3779488
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:L I SZWEDA
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依托单位:
OXIDATIVE MODIFICATION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE
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批准号:3843251
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:L I SZWEDA
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依托单位:
海外基金