Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome

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Abstract

Current knowledge on gamma glutamyl transpeptidase (gammaGTP) was reviewed. This enzyme, which is mainly expresses on the cell surface, is thought to participate in catalyzing glutathione breakdown, resulting in the formation of cystein, a thiol compound exerting antioxidant effects. The most important role of this enzyme in vivo seems to recover cystein from extracellular glutathione to preserve intracellular homeostasis of oxidative stress. Increase in environmental oxidative stress may induce this enzyme via NFkB. However, its excessive induction may contrary raise oxidative stress and cause subsequent organ injuries since cysteinylglycine, an intermediate of the glutathione breakdown, affects the iron metabolism, resulting in the production of free radicals. Recently, there are multiple lines of evidence that the development of hypertension, hyperlipidemia, diabetes mellitus is associated with increased serum gammaGTP levels. The oxidative stress derived from gammaGTP may participate in the development of these morbid conditions and would account for these associations. However, since subjects associated with excessive drinking and overweight, two major factors increasing serum gammaGTP level are usually suffering from hypertension, hyperlipidemia, diabetes mellitus, it is most likely that the associations are attributed to excessive drinking and overweight. We recently demonstrated that level of serum gammaGTP is inversely associated with that of serum adiponectin, a sort of adipocytokines. In that abnormalities of adipocytokines including adiponectin cause hypertension, hyperlipidemia, diabetes mellitus as well as fatty liver that is associated with increased gammaGTP level, the status of adipocytokines may stand behind the associations among these factors in obese subjects. Moreover, we demonstrated that serum gammaGTP level is inversely associated with subjects' statuses of lifestyles evaluated by Breslow's lifestyle index, suggesting that serum gammaGTP activity could be a tool for screening of subjects with unhealthy lifestyles. In that unhealthy lifestyles cause various morbid conditions designated as lifestyle-related diseases that is thought to comprehend metabolic syndrome and/or alcohol-related diseases, such screening and intervention in their correction should be significant to prevent their development. The consensus currently reached is that increased serum gammaGTP activity is associated with increased mortality. In that excessive drinking, obesity, as well as improper lifestyle elevate serum gammaGTP activity meanwhile cause various morbid conditions that make lifespan shorter, the view is not surprising.

Original languageEnglish
Pages (from-to)110-124
Number of pages15
JournalNihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
Volume42
Issue number3
Publication statusPublished - 2007 Jun

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gamma-Glutamyltransferase
hypertension
chronic illness
cause
Life Style
Serum
Adipokines
Disease
Oxidative Stress
Hyperlipidemias
Drinking
Glutathione
life-span
Diabetes Mellitus
induction
Adiponectin
Hypertension
mortality
alcohol
cysteinylglycine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Health(social science)

Cite this

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title = "Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome",
abstract = "Current knowledge on gamma glutamyl transpeptidase (gammaGTP) was reviewed. This enzyme, which is mainly expresses on the cell surface, is thought to participate in catalyzing glutathione breakdown, resulting in the formation of cystein, a thiol compound exerting antioxidant effects. The most important role of this enzyme in vivo seems to recover cystein from extracellular glutathione to preserve intracellular homeostasis of oxidative stress. Increase in environmental oxidative stress may induce this enzyme via NFkB. However, its excessive induction may contrary raise oxidative stress and cause subsequent organ injuries since cysteinylglycine, an intermediate of the glutathione breakdown, affects the iron metabolism, resulting in the production of free radicals. Recently, there are multiple lines of evidence that the development of hypertension, hyperlipidemia, diabetes mellitus is associated with increased serum gammaGTP levels. The oxidative stress derived from gammaGTP may participate in the development of these morbid conditions and would account for these associations. However, since subjects associated with excessive drinking and overweight, two major factors increasing serum gammaGTP level are usually suffering from hypertension, hyperlipidemia, diabetes mellitus, it is most likely that the associations are attributed to excessive drinking and overweight. We recently demonstrated that level of serum gammaGTP is inversely associated with that of serum adiponectin, a sort of adipocytokines. In that abnormalities of adipocytokines including adiponectin cause hypertension, hyperlipidemia, diabetes mellitus as well as fatty liver that is associated with increased gammaGTP level, the status of adipocytokines may stand behind the associations among these factors in obese subjects. Moreover, we demonstrated that serum gammaGTP level is inversely associated with subjects' statuses of lifestyles evaluated by Breslow's lifestyle index, suggesting that serum gammaGTP activity could be a tool for screening of subjects with unhealthy lifestyles. In that unhealthy lifestyles cause various morbid conditions designated as lifestyle-related diseases that is thought to comprehend metabolic syndrome and/or alcohol-related diseases, such screening and intervention in their correction should be significant to prevent their development. The consensus currently reached is that increased serum gammaGTP activity is associated with increased mortality. In that excessive drinking, obesity, as well as improper lifestyle elevate serum gammaGTP activity meanwhile cause various morbid conditions that make lifespan shorter, the view is not surprising.",
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