sinusoids central vein portal vein bile canaliculi bile duct hepatic artery LIVER STRUCTURE
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
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
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
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
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 SUBSTANCES IN LIVER • Phase Iand 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.
General ways of xenobiotics biotransformation and their localization in cell
PHASE I Hydrolysis 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.
Oxidation Alcohol 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 – inendoplasmic 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.
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