The Biotin‐Dependent Enzymes

Moss, Joel; Lane, .

doi:10.1002/9780470122808.ch7

Cited by 127 publications

(73 citation statements)

References 642 publications

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“…Importantly, these events occurred within the same time frame (10-20 min). ACC, the key regulatory enzyme of fatty acid biosynthesis (23)(24)(25)(26)(27)(28), is phosphorylated/inactivated by AMPK (13,14). As shown in the present study, the central administration of glucose, which increased hypothalamic ATP (Fig.…”

Section: Effect Of Centrally Administered Fructose and Glucose On Hypmentioning

confidence: 51%

Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake

Hun

Wolfgang²,

Tokutake

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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171

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The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonylCoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl-CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl-CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl-CoA hypothesis.acetyl-CoA carboxylase ͉ AMP kinase ͉ high-fructose corn syrup ͉ hypothalamic ATP ͉ obesity O ver the past three decades there has been an alarming increase in the incidence of obesity and type 2 diabetes in the United States (1). Particularly troubling is the rise of these conditions in youth (2). Paralleling this rise has been the extensive use of high-fructose sweeteners in the diet and increasing evidence that fructose may be a contributing factor to the obesity epidemic (3). These correlations are consistent with the finding that high-fructose diets promote insulin resistance, glucose intolerance, and increased rates of hepatic lipogenesis in laboratory animals (4).Although both glucose and fructose enter metabolism via the glycolytic pathway, the initial steps of hepatic fructose metabolism differ from those of glucose. Likewise, recent evidence suggests that sugar metabolism in regions of the central nervous system (CNS) that control food intake and energy expenditure, fructose metabolism also differs from that of glucose. It is known that the initial steps of hepatic fructose metabolism use a different set of enzymes that allow this sugar to bypass the rate-limiting step [catalyzed by phosphofructokinase (PFK)] in the glycolytic pathway. Similar enzymes of fructose metabolism are found in regions of the CNS that play an important role in monitoring energy balance and satiety control (5-7). These findings are consistent with a recent report (ref. 8 and findings reported herein) that centrally-administered fructose provokes feeding. In contrast, the central administration of glucose causes satiety (8,9). In this article, we provide a molecular basis for these differences. It should be noted, however, that uncertainty remains regarding the extent to which fructose in systemic circulation can cross the blood-brain barrier to enter these regions of the brain ...

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Section: Effect Of Centrally Administered Fructose and Glucose On Hypmentioning

confidence: 51%

Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake

Hun

Wolfgang²,

Tokutake

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

171

132

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“…As biotin serves as a cofactor for a number of liver enzymes (Moss and Lane, 1971), it is found at high levels in hepatocytes. We found that streptavidin conjugated to the fluorophore CY3 (CY3-SA) labels the liver in day 5 embryos (Fig.…”

Section: Resultsmentioning

confidence: 99%

A genetic screen in zebrafish identifies the mutantsvps18, nf2andfoie grasas models of liver disease

et al. 2005

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Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of embryogenesis in 297 zebrafish lines bearing mutations in genes that are essential for embryonic development. Seven mutants were identified, and three have phenotypes resembling different liver diseases. Mutation of the class C vacuolar protein sorting gene vps18results in hepatomegaly associated with large, vesicle-filled hepatocytes,which we attribute to the failure of endosomal-lysosomal trafficking. Additionally, these mutants develop defects in the bile canaliculi and have marked biliary paucity, suggesting that vps18 also functions to traffic vesicles to the hepatocyte apical membrane and may play a role in the development of the intrahepatic biliary tree. Similar findings have been reported for individuals with arthrogryposis-renal dysfunction-cholestasis(ARC) syndrome, which is due to mutation of another class C vps gene. A second mutant, resulting from disruption of the tumor suppressor gene nf2,develops extrahepatic choledochal cysts in the common bile duct, suggesting that this gene regulates division of biliary cells during development and that nf2 may play a role in the hyperplastic tendencies observed in biliary cells in individuals with choledochal cysts. The third mutant is in the novel gene foie gras, which develops large, lipid-filled hepatocytes, resembling those in individuals with fatty liver disease. These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease.

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“…1,2) These biotin-dependent carboxylases transform into holocarboxylases as a result of covalent binding between a specific lysine residue of apocarboxylases and biotin in the presence of holocarboxylase synthetase (HCS). 3) In addition to these well-known roles, novel functions of biotin have been reported.…”

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confidence: 99%

Effect of Biotin Treatment on Hepatic Gene Expression in Streptozotocin-Induced Diabetic Rats

Sugita

Shirakawa

Sugimoto

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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The Biotin‐Dependent Enzymes

Cited by 127 publications

References 642 publications

Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake

Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake

A genetic screen in zebrafish identifies the mutantsvps18, nf2andfoie grasas models of liver disease

Effect of Biotin Treatment on Hepatic Gene Expression in Streptozotocin-Induced Diabetic Rats

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