Metabolism of Nutrients in Liver Anusorn Cherdthong Ph

Metabolism of Nutrients in Liver Anusorn Cherdthong, Ph. D 137748 Applied Biochemistry in Nutritional Science Email: anusornc@kku. ac. th E-learning: http: //ags. kku. ac. th/e. Learning/137748

Introduction Role of liver: ØBiosynthesis ØMetabolic regulation ØInactivation or detoxification ØSecretion

Liver metabolism Ruminant Riis (1983)

Liver metabolism Non-ruminant Riis (1983)

Carbohydrate metabolism Major metabolism: q. Glycolysis q. Pentose phosphate pathway : PPP or hexose monophosphate shunt : HMS q. Gluconeogenesis q. Glycogenolysis q. Glycogenesis

Glycolysis or Embden-Meyerhof Minus Pathway ØConsisted of 11 reaction ØProduct: (1 glucose) ØPyruvate Ø 2 ATP Mc. Donald et al. (2011)

Krebs cycle q. Occurred at mitocondria q. Oxidation acetyl Co A —H 2 O, CO 2 q. Consisted 9 reactions q. Product: 3 NADH 3, 1 FADH 2 , 1 GTP Mc. Donald et al. (2011)

Pentose phosphate pathway q. Occurred at cytosol q. Provided NADPH, ribose Mc. Donald et al. (2011)

Gluconeogenesis qglucokinase Km 10 m. M (nonruminant) q. Hexokinase KM 0. 010. 1 m. M (ruminant) q Substrate are glucogenic, amino acids, lactate, pyruvate, glycerol, propionate q. Consisted of 3 reaction Mc. Donald et al. (2011)

Gluconeogenesis Substrates Mc. Donald et al. (2011)

Carbohydrate metabolism Glycogenolysis q. Lysis of glycogen when needed q. Appeared in live and musle q. End products are lactate or pyruvate q. Required enzyme phosphorylase a

Carbohydrate metabolism Glycogenesis q synthesis of glycogen q. Occurred at liver and muscle q Required enzyme glycogen synthetase

Protein metabolism Major metabolism q. Amino acids degradation q Amino synthesis q. Regulation of protein synthesis q. Protein degradation

Protein metabolism Amino acids degradation q. AA was used for energy source q End products are amino group and carbon skeleton q Ex: alanine degradation q. Pyruvate, aspatice acid q. Oxaloacetate, glutamate q -ketoglutarate q 2 reactions are deamination, carbon skeletal pathway

Utilization of C skeleton Mc. Donald et al. (2011)

Mc. Donald et al. (2011) Urea cycle q 1 urea/ 4 ATP q. Excrete via urine

Protein metabolism Amino synthesis q Biosynthesis of non-essential amino acids q. Required glutamate dehydrogenase q. NADP as Co A q. ATP q Re-used ammonia for synthesis q Consisted of oxidation and tranamination reaction

Protein metabolism Regulation of protein synthesis q. Control by RNA content in muscle, ATP and initiation process q. Occurred ribosomes q high synthesis rate when fasting

Protein metabolism Protein degradation q. Enzymes: endoenzymes and exoenzymes q. Endoenzymes: cathepsins B and D—short chain polypeptide q. Exoenzymes---degrade polypeptide to AA q. Cathepsins B-- albumin, ribonuclease and cytochrome C q. Cathepsins D--- haemoglobin q. Aminopeptidease D and alanine aminopeptidases degrade peptide at Nterminal

Lipid metabolism Major metabolism q. Lipolysis q. Glycerol lysis q. Fatty acid biosynthesis q. Biosynthesis of triacylglycerols q. Biosynthesis of cholesterol q. Biosynthesis of glycerol q. Ketone bodies

Lipid metabolism Lipolysis q. Required glycerol 3 -phosphate q. Major reaction is -oxidation q. Occurred in mitochondria q Acyl Co A form q. Carnitine transfer Acyl Co A across inner mitochondreia and need Carnitine acyltransferase I

Lipid metabolism Lipolysis q -oxidation—degrade FA on C beta q 4 step of -oxidation q. Dehydrogenation 1 q. Hydration q. Dehydrogenation 2 q. Thiolytic cleavage q 2 atom C are end product

Lipid metabolism Glycerol lysis q. For energy source q Start from fructose-1, 6 diphosphate— glycolysis—pyruvate—TCA q 44 ATP/ 2 Glycerol

Lipid metabolism Fatty acid biosynthesis q. Occurred when sufficient energy, high Acetyl Co. A q. Require NADPH q. Store as tryacylglecerol q. Consisted 2 sinthesis systems q. De novo synthesis q. Saturated FA with more than 16 C

Lipid metabolism Biosynthesis of triacylglycerols q. Occurred when more CHO q. Substrates are FA (Fatty acyl-Co A ) and glycerol (Glycerol-3 -phosphate) q. Diacylglycerol-3 -phosphate was found in reaction q 1, 2 -Diacylglycerol +Fatty acyl-Co A = triacylglycerols

Lipid metabolism Biosynthesis of cholesterol q. Normally found in Liver q. LDL carrier cholesterol to other organs q 3 step of biosynthesis: q. Synthesis mevalonate from acetyl Co A q. Synthesis squalene from mevalonate q. Synthesis cholesterol from squalene

Lipid metabolism Biosynthesis of glycerol q. Synthesis from glucose via glycolysis q. Start with dihydroxyacetone phosphate--glyceral- 3 –phosphate--- phospho diglyceride--- diacylglycerol--triacylglycerol

Lipid metabolism Ketone bodies q. Occurred when starvation q. Namely: Acetone, acetoacetate and D- hydroxybutyrate q Ketone bodies were transfer to organ for energy q. Enzyme require: thiolase, HMG-Co A synthase, HMG-Co A lyase, D- hydroxybutyrate dehydrogenase and acetoacetate decarboxylase q. Ketosis: high accumulated of KB

Conclusion 1 Metabolism of nutrient in liver 2 3 4 Carbohydrate metabolism : Glycolysis, PPP, Gluconeogenes, Glycogenolysis and Glycogenesis Protein metabolism : AA metabolism, urea cycle, protein metabolism Lipid metabolism : Lipolysis, glycerol lysis, fatty acid, triacylglycerols, cholesterol Ketone bodies

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