1. Biochemical functions of liver1

2. LIVER STRUCTURE sinusoids central vein portal vein bile canaliculi
hepatic artery
bile duct
sinusoids
bile canaliculi
central vein 2

3. LIVER FUNCTIONS Distribution of nutrients
All types of metabolism (protein, lipid, carbohydrate, vitamin, mineral)
Excretory (bile acids, urea synthesis)
Destruction of toxic substances
Depot of iron, vitamins 3

4. METABOLISM OF CARBS IN LIVER
glycolisis
metabolism of fructose and galactose
gluconeogenesis
release of glucose into blood (maintain the stable glucose concentration in blood)
conversion of pyruvate into acetyl CoA
tricarboxylic acid cycle
pentose phosphate pathway
glycogenolysis, glycogenogenesis 4

5. METABOLISM OF LIPIDS IN LIVER
synthesis of lipoproteins
synthesis of triacylglyserols
synthesis of phospholipids
synthesis of fatty acids, elongation of fatty acids chain, desaturation
synthesis of cholesterol
ketone bodies formation
lipolysis
fatty acids oxidation 5

6. METABOLISM OF PROTEINS IN LIVER
protein synthesis, including blood plasma proteins
protein decomposition; urea synthesis
conversion of proteins into carbs and lipids
interconversion of aminoacids
conversion of proteins into low molecular weight nitrogen containing substances 6

7. VITAMIN METABOLISM IN LIVER
Formation of active form of vitamin D
Formation of vitamin A from carotins
Depo of cyanocobalamine and folic acid
Depo of vitamin E
Phosphorilation of vitamins B, formation of coenzyme forms 7

8. DETOXIFICATION OF TOXIC SUBSTANCES IN LIVER
Phase I and phase II.
Phase I:
hydrolysis,
reduction,
oxidation.
These reactions introduce functional group (—OH, —NH2, —SH, or —COOH) and usually result in a little increase of hydrophylic properties 8

9. conjugation with glutathione,
Phase II includes:
glucuronation,
sulfation,
acetylation,
methylation,
conjugation with glutathione,
conjugation with aminoacids (glycin, taurin, glutamic acid)
Phase II results in the marked increase of hydrophylic properties of xenobiotic. 9

10. General ways of xenobiotics biotransformation and their localization in cell
REACTION
ENZYME
LOCALIZATION
PHASE I
Hydrolysis
Reduction
Oxidation
Esterase
Peptidase Epoxide hydrolase
Azo- and nitro-reduction
Carbonyl reduction
Disulfide reduction
Sulfoxide reduction
Alcohol dehydrogenase
Aldehyde dehydrogenase
Aldehyde oxidase
Xanthine oxidase
Monoamine oxidase
Diamine oxidase
Flavin-monooxygenases
Cytochrome P450
Microsomes, cytosol, lysosomes, blood lysosomes Microsomes, cytosol
Microflora, microsomes, cytosol
Cytosol, blood, microsomes
Cytosol
Mitochondria, cytosol
Mitochondria
Microsomes
PHASE II
Glucuronide conjugation
Sulfate conjugation
Glutathione conjugation
Amino acid conjugation
Acetylation
Methylation
Cytosol, microsomes
Mitochondria, microsomes
Cytosol, microsomes, blood 10

11. PHASE I Hydrolysis Reduction
Esterases (carboxyesterases, cholinesterases, phosphatases)
Peptidases
Reduction
Metals and xenobiotics containing aldehyde, keto, disulfide, alkyn, azo, or nitro group are often reduced
Reducing agents:
Reduced glutathione,
FADH2,
FMN,
NADH
NADPH. 11

12. Alcohol dehydrogenase
Oxidation
Alcohol dehydrogenase 12

13. Aldehyde dehydrogenase Xanthine dehydrogenase-Xanthine oxidase
Oxidizes aldehydes to carbonic acids
Xanthine dehydrogenase-Xanthine oxidase
Monoaminooxidase
Oxidative deamination of amines (serotonin) and many xenobiotics 13

14. Cytochrom P450
The highest concentration – in endoplasmic reticulum of hepatocytes (microsomes).
Hem containing protein.
Catalyzes monooxigenation of oxygen atom into substrate; another oxygen atom is reduced to water
Electrons are transferred from NADPH to cytochrome P450 through flavoprotein NADPH-cytochrome P450 reductase. 14

15. SCHEME OF MONOOXYGENASE SYSTEM15

16. 16

17. The example of reaction that is catalyzed by cytochrome P450: hydroxylation of aliphatic carbon17

18. The example of reaction that is catalyzed by cytochrome P450: hydroxylation of aromatic carbon18