Metabolism of Nutrients in Liver
Anusorn Cherdthong, PhD
137748 Applied Biochemistry in Nutritional Science
Email: anusornc@kku.ac.th
E-learning: http://ags.kku.ac.th/eLearning/137748
Introduction
Role of liver:
Biosynthesis
Metabolic regulation
Inactivation or detoxification
Secretion
Liver metabolism
Ruminant
Riis (1983)
Liver metabolism
Non-ruminant
Riis (1983)
Carbohydrate metabolism
Major metabolism:
Glycolysis
Pentose phosphate pathway : PPP or
hexose monophosphate shunt : HMS
Gluconeogenesis
Glycogenolysis
Glycogenesis
Glycolysis or
Embden-Meyerhof
Minus Pathway
Consisted of 11
reaction
Product: (1
glucose)
Pyruvate
2 ATP
McDonald et al. (2011)
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)
Pentose phosphate
pathway
Occurred at cytosol
Provided NADPH, ribose
McDonald et al. (2011)
Gluconeogenesis
glucokinase Km 10
mM (nonruminant)
Hexokinase KM 0.010.1 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
Glycogenolysis
Lysis of glycogen when needed
Appeared in live and musle
End products are lactate or pyruvate
Required enzyme phosphorylase a
Carbohydrate metabolism
Glycogenesis
 synthesis of glycogen
Occurred at liver and muscle
 Required enzyme glycogen
synthetase
Protein metabolism
Major metabolism
Amino acids degradation
 Amino synthesis
Regulation of protein synthesis
Protein degradation
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
Utilization of C skeleton
McDonald et al. (2011)
McDonald et al. (2011)
Urea cycle
1 urea/ 4 ATP
Excrete via urine
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
Protein metabolism
Regulation of protein synthesis
Control by RNA content in muscle, ATP
and initiation process
Occurred ribosomes
 high synthesis rate when fasting
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 Nterminal
Lipid metabolism
Major metabolism
Lipolysis
Glycerol lysis
Fatty acid biosynthesis
Biosynthesis of triacylglycerols
Biosynthesis of cholesterol
Biosynthesis of glycerol
Ketone bodies
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
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
Lipid metabolism
Glycerol lysis
For energy source
 Start from fructose-1,6 diphosphate—
glycolysis—pyruvate—TCA
 44 ATP/ 2 Glycerol
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
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
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
Lipid metabolism
Biosynthesis of glycerol
Synthesis from glucose via glycolysis
Start with dihydroxyacetone phosphate--glyceral- 3 –phosphate--- phospho
diglyceride--- diacylglycerol--triacylglycerol
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
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
Thank you!