Metabolism of Nutrients in Liver

1. Metabolism of Nutrients in Liver AnusornCherdthong, PhD 137748 Applied Biochemistry in Nutritional Science Email: anusornc@kku.ac.th • E-learning: http://ags.kku.ac.th/eLearning/137748

2. Introduction • Role of liver: • Biosynthesis • Metabolic regulation • Inactivation or detoxification • Secretion

3. Liver metabolism Ruminant Riis (1983)

4. Liver metabolism Non-ruminant Riis (1983)

5. Carbohydrate metabolism • Major metabolism: • Glycolysis • Pentose phosphate pathway : PPP or hexosemonophosphate shunt : HMS • Gluconeogenesis • Glycogenolysis • Glycogenesis

6. Glycolysis or Embden-Meyerhof Minus Pathway • Consisted of 11 reaction • Product: (1 glucose) • Pyruvate • 2 ATP McDonald et al. (2011)

7. Krebs cycle • Occurred at mitocondria • Oxidation acetyl Co A—H2O, CO2 • Consisted 9 reactions • Product: 3 NADH 3, 1 FADH2 , 1GTP McDonald et al. (2011)

8. Pentose phosphate pathway • Occurred at cytosol • Provided NADPH, ribose McDonald et al. (2011)

9. Gluconeogenesis • glucokinase Km 10 mM (nonruminant) • Hexokinase KM 0.01-0.1mM(ruminant) • Substrate are glucogenic, amino acids, lactate, pyruvate, glycerol, propionate • Consisted of 3 reaction McDonald et al. (2011)

10. Gluconeogenesis Substrates McDonald et al. (2011)

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

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

13. Protein metabolism • Major metabolism • Amino acids degradation • Amino synthesis • Regulation of protein synthesis • Protein degradation

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

15. Utilization of C skeleton McDonald et al. (2011)

16. McDonald et al. (2011) • Urea cycle • 1 urea/ 4 ATP • Excrete via urine

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

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

19. Protein metabolism • Protein degradation • Enzymes: endoenzymesand exoenzymes • Endoenzymes: cathepsins B and D—short chain polypeptide • Exoenzymes---degrade polypeptide to AA • Cathepsins B-- albumin, ribonuclease andcytochrome C • Cathepsins D---haemoglobin • Aminopeptidease D andalanineaminopeptidases degrade peptide at N-terminal

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

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

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

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

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

25. Lipid metabolism • Biosynthesis of triacylglycerols • Occurred when more CHO • Substrates 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

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

27. Lipid metabolism • Biosynthesis of glycerol • Synthesis from glucose via glycolysis • Start with dihydroxyacetone phosphate---glyceral- 3 –phosphate---phosphodiglyceride---diacylglycerol---triacylglycerol

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

29. 1 2 3 4 Conclusion Metabolism of nutrient in liver 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 Ketonebodies

30. Thank you!