Anusorn Cherdthong, PhD 137748 Applied Biochemistry in Nutritional Science Email: [email protected] E-learning: http://ags.kku.ac.th/eLearning/137748 Metabolism of Nutrients in Liver
Jan 07, 2016
Anusorn Cherdthong, PhD137748 Applied Biochemistry in Nutritional Science
Email: [email protected]: http://ags.kku.ac.th/eLearning/137748
Metabolism of Nutrients in Liver
Introduction
Role of liver:BiosynthesisMetabolic regulationInactivation or detoxificationSecretion
Liver metabolism
Riis (1983)
Ruminant
Liver metabolism
Riis (1983)
Non-ruminant
Carbohydrate metabolism
Major metabolism:GlycolysisPentose phosphate pathway : PPP or hexose monophosphate shunt : HMS
GluconeogenesisGlycogenolysisGlycogenesis
Glycolysis or Embden-Meyerhof Minus PathwayConsisted of 11 reaction
Product: (1 glucose)
Pyruvate2 ATP
McDonald et al. (2011)
Krebs cycle Occurred at mitocondria
Oxidation acetyl Co A—H2O, CO2
Consisted 9 reactionsProduct: 3 NADH 3, 1 FADH2 , 1GTP McDonald et al.
(2011)
Pentose phosphate pathway Occurred at cytosolProvided NADPH, ribose
McDonald et al. (2011)
Gluconeogenesis glucokinase Km 10 mM (nonruminant)
Hexokinase KM 0.01-0.1 mM (ruminant)
Substrate are glucogenic, amino acids, lactate, pyruvate, glycerol, propionate
Consisted of 3 reaction
McDonald et al. (2011)
Gluconeogenesis Substrates
McDonald et al. (2011)
Carbohydrate metabolism
GlycogenolysisLysis of glycogen when neededAppeared in live and musleEnd products are lactate or pyruvateRequired enzyme phosphorylase a
Carbohydrate metabolism
Glycogenesis synthesis of glycogenOccurred at liver and muscle Required enzyme glycogen synthetase
Protein metabolism
Major metabolismAmino acids degradation Amino synthesisRegulation of protein synthesisProtein degradation
Protein metabolism
Amino acids degradationAA was used for energy source End products are amino group and carbon skeleton
Ex: alanine degradation Pyruvate, aspatice acidOxaloacetate, glutamate -ketoglutarate
2 reactions are deamination, carbon skeletal pathway
McDonald et al. (2011)
Utilization of C skeleton
Urea cycle1 urea/ 4 ATPExcrete via urine
McDonald et al. (2011)
Protein metabolism
Amino synthesis Biosynthesis of non-essential amino acids
Required glutamate dehydrogenaseNADP as Co AATP Re-used ammonia for synthesis Consisted of oxidation and tranamination reaction
Protein metabolism
Regulation of protein synthesisControl by RNA content in muscle, ATP and initiation process
Occurred ribosomes high synthesis rate when fasting
Protein metabolism
Protein degradationEnzymes: endoenzymes and exoenzymes Endoenzymes: cathepsins B and D—short chain polypeptide
Exoenzymes---degrade polypeptide to AACathepsins B-- albumin, ribonuclease and cytochrome C
Cathepsins D--- haemoglobin Aminopeptidease D and alanine aminopeptidases degrade peptide at N-terminal
Lipid metabolism
Major metabolismLipolysisGlycerol lysisFatty acid biosynthesisBiosynthesis of triacylglycerolsBiosynthesis of cholesterolBiosynthesis of glycerolKetone bodies
Lipid metabolism
LipolysisRequired glycerol 3-phosphate Major reaction is -oxidationOccurred in mitochondria Acyl Co A formCarnitine transfer Acyl Co A across inner mitochondreia and need Carnitine acyltransferase I
Lipid metabolism
Lipolysis-oxidation—degrade FA on C beta4 step of -oxidation
Dehydrogenation 1HydrationDehydrogenation 2Thiolytic cleavage
2 atom C are end product
Lipid metabolism
Glycerol lysisFor energy source Start from fructose-1,6 diphosphate—glycolysis—pyruvate—TCA
44 ATP/ 2 Glycerol
Lipid metabolism
Fatty acid biosynthesisOccurred when sufficient energy, high Acetyl CoA
Require NADPHStore as tryacylglecerolConsisted 2 sinthesis systems
De novo synthesisSaturated FA with more than 16 C
Lipid metabolism
Biosynthesis of triacylglycerolsOccurred when more CHOSubstrates are FA (Fatty acyl-Co A ) and glycerol (Glycerol-3-phosphate)
Diacylglycerol-3-phosphate was found in reaction
1,2-Diacylglycerol +Fatty acyl-Co A = triacylglycerols
Lipid metabolism
Biosynthesis of cholesterolNormally found in LiverLDL carrier cholesterol to other organs3 step of biosynthesis:
Synthesis mevalonate from acetyl Co A
Synthesis squalene from mevalonateSynthesis cholesterol from squalene
Lipid metabolism
Biosynthesis of glycerolSynthesis from glucose via glycolysisStart with dihydroxyacetone phosphate--- glyceral- 3 –phosphate--- phospho diglyceride--- diacylglycerol--- triacylglycerol
Lipid metabolism
Ketone bodiesOccurred when starvationNamely: Acetone, acetoacetate and D--hydroxybutyrate
Ketone bodies were transfer to organ for energy
Enzyme require: thiolase, HMG-Co A synthase, HMG-Co A lyase, D--hydroxybutyrate dehydrogenase and acetoacetate decarboxylase
Ketosis: high accumulated of KB
Conclusion
1
2
Metabolism of nutrient in liver
Carbohydrate metabolism : Glycolysis, PPP, Gluconeogenes, Glycogenolysis and Glycogenesis
3Protein metabolism : AA metabolism, urea cycle, protein metabolism
4Lipid metabolism : Lipolysis, glycerol lysis, fatty acid, triacylglycerols, cholesterol Ketone bodies
Thank you!