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

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

3. Liver metabolism Riis (1983) Ruminant

4. Liver metabolism Riis (1983) Non-ruminant

5. Carbohydrate metabolism Major metabolism:  Glycolysis  Pentose phosphate pathway : PPP or hexose monophosphate 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 FADH 2, 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- 0.1 mM (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. McDonald et al. (2011) Utilization of C skeleton

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

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: endoenzymes and exoenzymes  Endoenzymes: cathepsins B and D—short chain polypeptide  Exoenzymes---degrade polypeptide to AA  Cathepsins B-- albumin, ribonuclease and cytochrome C  Cathepsins D--- haemoglobin  Aminopeptidease D and alanine aminopeptidases 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 Carnitine acyltransferase 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 from acetyl Co A  Synthesis squalene from mevalonate  Synthesis cholesterol from squalene

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

28. Lipid metabolism Ketone bodies  Occurred when starvation  Namely: 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

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

30. Thank you!