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Hormone Major Metabolic Control Hormones Second Receptor Mechanism messenger Insulin (51 amino Tyrosine acid heterodimeric kinase peptide) Phosphorylated proteins Target tissues Liver, muscle, adipose, pancreas, many others Enzyme activity Gene transcription decreased cAMP Enzyme activity Glucagon (29 amino acid peptide) G-protein coupled Cortisol (steroid) Transcription Altered level of factor specific mRNA Epinephrine (tyrosine derivative) G-protein coupled (at least four types) cAMP Growth hormone (191 amino acid protein) Cytokine family cell surface Tyrosine kinase !"#$%&'($) *%$+,-(.' cAMP decreased cAMP Sometimes gene transcription Liver, pancreas Gene transcription Nearly all Enzyme activity Liver, muscle, adipose, brain, pancreas, cardiovascular PI hydrolysis Enzyme activity Liver, muscle, adipose; others mediated by IGF-I Sometimes gene transcription PI hydrolysis !"#$% 6037$#. 6057$8.) ;<.0.'10,+3#70. 6037$#. 6057$8.) !+()$,17(-# /%$'.() !-(&$#.,'(##3. !"#$%&"' 99! /01#+1 23'%(.)'# ()%&#"* 4(-).5 =%1() >.1%' :!6 Regulation of Liver Metabolism Pathway Regulatory enzyme Stimulators Glycolysis Glucokinase Phosphofructokinase TCA Cycle Glycogen synthesis Glycogen breakdown Hexose monophosphate Urea cycle Fatty acid synthesis Ketone body synthesis Cholesterol synthesis Purine synthesis Pyrimidine synthesis Hormones affecting enzyme activity Citrate, ketone bodies, ATP, phosphoenolpyruvate ATP, alanine Insulin Glucagon Epinephrine (all via altered [F2,6bP]) Insulin Glucagon Epinephrine Glucagon Fructose 2,6bisphosphate, AMP Insulin Glucagon Epinephrine CoA, NAD, ADP, pyruvate, Ca2+ Acetyl-CoA Acetyl-CoA, NADH, ATP ADP Insulin Citrate synthase NAD, (TCA cycle intermediates) Isocitrate dehydrogenase -ketoglutarate dehydrogenase Glycogen synthase ADP, Ca2+ Citrate, Long chain acyl-CoA, ATP, NADH, succinyl-CoA ATP, NADH Pyruvate kinase Gluconeogenesis (High plasma glucose) Fructose 2,6bisphosphate, AMP AMP, Fructose1,6-bisphosphate Inhibitors Phosphoenolpyruvate carboxykinase Fructose 1,6bisphosphatase Glucose-6phosphatase Pyruvate dehydrogenase Pyruvate carboxylase Glycogen phosphorylase Glucose-6-phosphate dehydrogenase Glutamate dehydrogenase Carbamoyl phosphate synthetase I Acetyl-CoA carboxylase HMG-CoA synthase Ca2+ Glucose-6phosphate AMP ATP, NADH, succinyl-CoA, GTP Glycogen NADP Glucose-6-phosphate, ATP NADPH ADP ATP, GTP, NADH N-acetylglutamate (substrate) Citrate Long-chain acyl-CoA Ribose-phosphate pyrophosphokinase PRPP glutamyl PRPP amidotransferase Carbamoyl phosphate ATP, PRPP synthetase II Aspartate transcarbamoylase Insulin Cortisol Insulin Cortisol Glucagon Insulin Cortisol Insulin Cortisol Insulin Cortisol Glucagon Insulin Glucagon Epinephrine Insulin Glucagon Epinephrine Insulin Cortisol Insulin Insulin Glucagon Acetyl-CoA HMG-CoA reductase Hormones affecting enzyme levels Insulin Cortisol Insulin Cortisol Insulin Glucagon Cholesterol, bile acids Adenine, Guanine and Thymine nucleotides Adenine and Guanine nucleotides Uridine nucleotides, GTP CTP Insulin Glucagon Regulation of Skeletal Muscle Metabolism Pathway Glycolysis Regulatory enzyme Glucose transporter (GLUT 4) Hexokinase Phosphofructokinase Glycogen synthesis Glycogen synthase Glycogen breakdown Protein synthesis Glycogen Phosphorylase Transcription and translation initiation Protein breakdown Protease activation Stimulators Inhibitors (Muscle contraction) Fructose 2,6bisphosphate, AMP, (Muscle contraction) Glucose-6phosphate, low Glycogen levels Ca2+, AMP Hormones affecting enzyme activity Insulin Cortisol (change amount in plasma membrane) Glucose-6-phosphate Citrate, ketone bodies, ATP Hormones affecting enzyme levels Insulin Cortisol Cortisol Ca2+, AMP Insulin Epinephrine Glucose-6-phosphate, ATP Insulin Epinephrine Insulin Insulin Growth hormone Androgens Cortisol Insulin Cortisol Regulation of Adipose Tissue Metabolism Pathway Glycolysis Regulatory enzyme Glucose transporter (GLUT 4) Hexokinase Phosphofructokinase Triacylglycerol synthesis Triacylglycerol breakdown Lipoprotein lipase Glycerol phosphate acyltransferase Hormone-sensitive lipase Stimulators Fructose 2,6bisphosphate, AMP, (Muscle contraction) (high VLDL, chylomicrons) Inhibitors Hormones affecting enzyme activity Insulin Cortisol (change amount in plasma membrane) Glucose-6-phosphate Citrate, ketone bodies, ATP Hormones affecting enzyme levels Insulin Cortisol Cortisol Insulin (low glycerol phosphate levels) Insulin Epinephrine Insulin Cortisol Oxidative Phosphorylation and Photo-phosphorylation (ATP synthase) NH2 Adenosine Diphosphate (ADP) N O O OH H OH H G´° = +30.5 kJ/mol O H N O O O N O P O P O P O CH2 O O O O H H H H OH OH O O P OH + H N N N O O N O P O P O CH2 O NH2 Adenosine Triphosphate (ATP) N Inorganic phosphate + H2O Substrate-Level Phosphorylation (Pyruvate kinase) NH2 Adenosine Diphosphate (ADP) O N O P O O + O O O + O P O P O CH2 O O C C CH2 O Phosphoenolpyruvate O H OH H OH H O O H2O O C C CH3 G´° = –31.7 kJ/mol H N N N N NH2 Adenosine Triphosphate (ATP) N N O O O N O P O P O P O CH2 O + Pyruvate O O O H H OH H OH H Phosphoglycerate kinase Succinyl-CoA synthetase ATP Buffers NH2 Adenosine Diphosphate (ADP) O O O P O P O CH2 O O O H OH H OH O P O P O CH2 O O H H OH H OH H Adenylate kinase G´° = +2.0 kJ/mol O O O N O P O P O CH2 O O O + H H OH H OH H OH H OH O O CH3 N H N NH Phosphocreatine O P O O G´° = –12.6 kJ/mol O O CH3 N NH2 NH Creatine + H OH H OH NH2 N N Creatine kinase H H Adenosine Triphosphate (ATP) N O H N O N O P O CH2 O + H H Adenosine Monophosphate NH2 (AMP) N N N O O O N O P O P O P O CH2 O N N O N N N N NH2 Adenosine Diphosphate (ADP) O O O H H O + NH2 Adenosine Triphosphate (ATP) N N N N NH2 Adenosine Diphosphate (ADP) N N O O O O O O N N O P O P O P O CH2 O H H OH H OH H ?> ?> @&().&A%(). `+,-%$.$%/"0 1$0$234% ?> 2>LD >B C &'_ &*) ? ? 0,5) 0,5) 7!E/FG.&.)-.)' /%$'.(),4()1#. 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