Regulation of Glucose Metabolism by Intracellular Compounds

Transcription

1 Regulation of Metabolism by Intracellular ompounds Hexokinase ( ) -6- H ribose-5- or fructose phosphate () ( ) H -6-phosphate GI GM UD-glucose pyrophosphorylase 1-phosphate UD- hosphorylase synthase () AM ( ) ( ) -6- () -6- () Low [glycogen] ( ) AM ( ) AM ( ) Fructose-2,6-bis Fructose bisphosphatase hosphofructokinase Fructose-1,6-bisphosphate ( ) ( ) itrate ( ) hosphoenolpyruvate () AM () Fructose-2,6-bis ( ) () AM () Fructose-1,6-bis hosphoenolpyruvate carboxykinase hosphoenolpyruvate kinase GD 2 GT xaloacetate (Malate) carboxylase xaloacetate () Acetyl-oA FBase-2 FK-2 bound to allosteric site FBase-2 FK-2 AM bound to allosteric site () Gluconeogenesis () Glycolysis

2 synthesis and breakdown H 2 H 2 H H H H hosphofructokinase-2 H 2 H 2 H H H!-D-!-D- H 2 H 2 H H H i Fructose bisphosphatase-2 H 2 H 2 H H H H!-D-!-D- Stereoview of hosphofructokinase-2/fructose-bis-phosphatase-2 (Rattus norvegicus, DB ID 1BIF)

3 TA ycle Regulatory Enzymes Enzyme Stimulators Inhibitors omments carboxylase Acetyl-oA Several hormones alter the amount of this enzyme: Insulin ortisol Glucagon oa-sh, AD, a 2, Mg 2, pyruvate, insulin Acetyl-oA, ADH, phosphorylation, and Effect of Mg 2 : binds Mg 2 with higher affinity than ; high free [Mg 2 ] means low []. Mg 2 and a 2 activate the phosphatase itrate synthase AD, oa-sh, High [oxaloacetate] and [acetyl-oa] itrate, Long chain acyl-oa,, ADH, succinyl- oa Isocitrate a 2,, ADH Isocitrate is the most important regulatory enzyme in the TA cycle α-ketoglutarate a 2 ADH, succinyl-oa

4 TA Substrates H 3 2 arboxylase i H 2 xaloacetate H 3 H H 2 Aspartate!-ketoglutarate Glutamate Aspartate aminotransferase H 2 xaloacetate H 2 H 2 AD H 4 ADH H 2 H 2 Glutamate H 3 H Glutamate!-ketoglutarate H 2 H Aspartate H 2 H H 3 H H 2 H H 2 H H H 4 AM deaminase H 2 H H GT GD H Adenylosuccinate synthetase H H 2 H H AM Adenylosuccinate lyase H H Adenosine Monophosphate (AM) Inosine Monophosphate (IM) Adenylosuccinate monophosphate Fumarate

5 Hormone Insulin (51 amino acid heterodimeric peptide) Homeostasis ontrol Hormones Second Receptor Mechanism messenger Tyrosine kinase hosphorylated proteins decreased cam Enzyme activity Gene transcription Target tissues Liver, muscle, adipose, pancreas, many others Glucagon (29 amino acid peptide) G-protein coupled cam Enzyme activity Sometimes gene transcription Liver, pancreas ortisol (steroid) Transcription factor Altered level of specific mra Gene transcription early all Epinephrine (tyrosine derivative) G-protein coupled (at least four types) cam decreased cam I hydrolysis Enzyme activity Liver, muscle, adipose, brain, pancreas, cardiovascular Growth hormone (191 amino acid protein) ytokine family cell surface Tyrosine kinase I hydrolysis Enzyme activity Sometimes gene transcription Liver, muscle, adipose; others mediated by IGF-I

6 Homeostasis Insulin ortisol H H H H 2 H H H Epinephrine H 3

7 Regulation of Metabolism (Liver) ortisol Amount of enzyme Insulin Amount of enzyme -6-phosphate H ribose-5- or () fructose-6- ( ) H ortisol enzyme ( ) AM ( ) Fructose-2,6-bis -6- phosphatase Glucokinase -6-phosphate GI Fructose bisphosphatase GM UD-glucose pyrophosphorylase hosphofructokinase Insulin Amount of enzyme ortisol Amount of enzyme 1-phosphate UD- hosphorylase synthase ( ) ( ) itrate ( ) hosphoenolpyruvate () AM () Fructose-2,6-bis () hosphorylation () AM ( ) ( ) -6- ortisol enzyme () -6- () Low [glycogen] ( ) AM ( ) hosphorylation Fructose-1,6-bisphosphate () hosphorylation ortisol enzyme ( ) ( ) Alanine ( ) hosphorylation () AM () Fructose-1,6-bis hosphoenolpyruvate carboxykinase hosphoenolpyruvate xaloacetate kinase GD 2 GT (Malate) carboxylase xaloacetate ortisol enzyme () Acetyl-oA FBase-2 FK-2 hosphorylated FBase-2 FK-2 (ot phosphorylated) () Gluconeogenesis () Glycolysis

8 Regulation of Metabolism (Skeletal Muscle) (outside cell) () Insulin () Muscle contraction ( ) ortisol Hexokinase ( ) -6- H ribose-5- or fructose phosphate () ( ) H ( ) AM ( ) Fructose-2,6-bis -6-phosphate GI Fructose bisphosphatase Fructose-1,6-bisphosphate GM UD-glucose pyrophosphorylase hosphofructokinase 1-phosphate UD- hosphorylase synthase ( ) ( ) itrate ( ) hosphoenolpyruvate () AM () Fructose-2,6-bis () AM ( ) ( ) -6- () -6- () Low [glycogen] ( ) AM ( ) alcium ( ) () AM () Fructose-1,6-bis Alanine Lactate hosphoenolpyruvate kinase Lactate Amino acids hosphoenolpyruvate carboxykinase xaloacetate GD 2 GT xaloacetate (Malate) () ortisol roteins FBase-2 FK-2 hosphorylated FBase-2 FK-2 (ot phosphorylated) () Glycolysis () Gluconeogenesis