biochemical functions of liver. portal vein hepatic artery bile duct sinusoids bile canaliculi...
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Biochemical functions Biochemical functions of liverof liver
portal vein
hepatic artery
bile duct
sinusoids
bile canaliculi
central vein
LIVER STRUCTURELIVER STRUCTURE
LIVER FUNCTIONSLIVER 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
METABOLISM OF CARBS IN METABOLISM OF CARBS IN LIVERLIVER
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
METABOLISM OF LIPIDS IN METABOLISM OF LIPIDS IN LIVERLIVER
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
METABOLISM OF PROTEINS IN METABOLISM OF PROTEINS IN LIVERLIVER
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
• 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
VITAMIN METABOLISM IN LIVER
DETOXIFICATION OF TOXIC DETOXIFICATION OF TOXIC SUBSTANCES IN LIVERSUBSTANCES 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
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.
REACTION ENZYME LOCALIZATION
PHASE I
Hydrolysis
Reduction
Oxidation
EsterasePeptidase Epoxide hydrolase
Azo- and nitro-reduction Carbonyl reductionDisulfide reductionSulfoxide reduction
Alcohol dehydrogenaseAldehyde dehydrogenaseAldehyde oxidaseXanthine oxidaseMonoamine oxidaseDiamine oxidaseFlavin-monooxygenasesCytochrome P450
Microsomes, cytosol, lysosomes, blood lysosomes Microsomes, cytosol
Microflora, microsomes, cytosolCytosol, blood, microsomesCytosolCytosol
CytosolMitochondria, cytosolCytosolCytosolMitochondriaCytosolMicrosomesMicrosomes
PHASE II
Glucuronide conjugationSulfate conjugationGlutathione conjugationAmino acid conjugationAcetylationMethylation
MicrosomesCytosol, microsomesCytosolMitochondria, cytosolMitochondria, microsomesCytosol, microsomes, blood
General ways of xenobiotics biotransformation and their localization in cell
PHASE I
Hydrolysis
Esterases (carboxyesterases, cholinesterases, phosphatases) Peptidases
ReductionMetals and xenobiotics containing aldehyde, keto, disulfide, alkyn, azo, or nitro group are often reduced
Reducing agents:Reduced glutathione, FADH2, FMN,NADH NADPH.
OxidationAlcohol dehydrogenase
Aldehyde dehydrogenase
Oxidizes aldehydes to carbonic acids
Xanthine dehydrogenase-Xanthine oxidase
Monoaminooxidase
Oxidative deamination of amines (serotonin) and many xenobiotics
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.
SCHEME OF MONOOXYGENASE SYSTEM
The example of reaction that is catalyzed by cytochrome P450: hydroxylation of aliphatic carbon
The example of reaction that is catalyzed by cytochrome P450: hydroxylation of aromatic carbon