Anusorn Cherdthong, PhD137748 Applied Biochemistry in Nutritional Science

Email: anusornc@kku.ac.thE-learning: 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!