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Short- and Long-Term Adaptation to Altered Levels of Glucose: Fifty Years of Scientific Adventure.
Uyeda, Kosaku.
Afiliação
  • Uyeda K; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; email: kosaku.uyeda@utsouthwestern.edu.
Annu Rev Biochem ; 90: 31-55, 2021 06 20.
Article em En | MEDLINE | ID: mdl-34153217
My graduate and postdoctoral training in metabolism and enzymology eventually led me to study the short- and long-term regulation of glucose and lipid metabolism. In the early phase of my career, my trainees and I identified, purified, and characterized a variety of phosphofructokinase enzymes from mammalian tissues. These studies led us to discover fructose 2,6-P2, the most potent activator of phosphofructokinase and glycolysis. The discovery of fructose 2,6-P2 led to the identification and characterization of the tissue-specific bifunctional enzyme 6-phosphofructo-2-kinase:fructose 2,6-bisphosphatase. We discovered a glucose signaling mechanism by which the liver maintains glucose homeostasis by regulating the activities of this bifunctional enzyme. With a rise in glucose, a signaling metabolite, xylulose 5-phosphate, triggers rapid activation of a specific protein phosphatase (PP2ABδC), which dephosphorylates the bifunctional enzyme, thereby increasing fructose 2,6-P2 levels and upregulating glycolysis. These endeavors paved the way for us to initiate the later phase of my career in which we discovered a new transcription factor termed the carbohydrate response element binding protein (ChREBP). Now ChREBP is recognized as the masterregulator controlling conversion of excess carbohydrates to storage of fat in the liver. ChREBP functions as a central metabolic coordinator that responds to nutrients independently of insulin. The ChREBP transcription factor facilitates metabolic adaptation to excess glucose, leading to obesity and its associated diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bioquímica / Fosfofrutoquinase-2 / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Frutosedifosfatos Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male País/Região como assunto: America do norte Idioma: En Revista: Annu Rev Biochem Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bioquímica / Fosfofrutoquinase-2 / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Frutosedifosfatos Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male País/Região como assunto: America do norte Idioma: En Revista: Annu Rev Biochem Ano de publicação: 2021 Tipo de documento: Article