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Biochemistry of liver

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Biochemistry of liver

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    1. Biochemistry of liver

    2. Function of Liver Synthesis of the essential component ex. Albumin Detoxification of drug and forign substances Excretory function ex. Bile excretion Storage function ex. Glucose, Fe +2, vit B12, Vit D Heamatological function Metabolism

    3. Diseases of the Liver Infectious diseases e.g. Viral hepatitis. Toxic hepatitis e.g. Alcoholic liver disease. Genetic diseases e.g. Hemochromatosis. Immune diseases e.g. Auto immune hepatitis. Tumors e.g. Benign or malignant

    4. Individuals seeking for investigations of liver function Apparently normal individual : for check. A patient C/o of easy fatigability, lossof apetite….etc A clinicaly diagnosed case.

    5. Liver Function Tests Serum Enzymes ALT : ( SGPT ) AST : ( SGOT ) ALP : Alkaline Phosphatase GGT: Gamma Glutamyl Trans Peptidase (GGTP ) LD: Lactate Dehydrogenase Bilirubin Albumin Prthrombin Time Iron and Ferritin

    6. AST & ALT Aspartate aminotransferase – Alanine aminotransferase AST & ALT : High in viral hepatitis AST & ALT : High in Toxic hepatitis AST & ALT : High in gall stones AST > ALT : in liver cirrhosis ALT is more liver specific than AST ALT rare increase in other conditions of liver diseases. AST : high in myocardial infraction AST : high in Muscle Diseases AST : high in Pulmonary embolism, hemolytic diseases, Crush muscle injuries and pancreatitis

    7. ALP Alkaline Phosphatase ALP used for investigation of Hepatobiliary diseases Bone diseases ALP high in Intra-hepatic biliary obst e.g. by cancer invasion. Extra-hepatic biliary obst e.g. by stone Paget s disease of bone During bone growth “ during childchood” After healing of bone fractions In pregnancy 3 rd trimester “ Placental isoenzymes”

    8. GGT ( Gamma Glutamyl Transferase ) NTP ( 5 nucleotidase ) GGT high in All liver diseases (and more sensitive than ALP) 1 ry& 2ry liver tumors In fatty liver and alcoholic patients Reference Range 1 - 24 in female 2 - 30 in male NTP ( 5 nucleotidase ) Is specific for hepatobiliary diseases.

    9. LD (Lactate Dehydrogenase) Specific in toxic hepatitis LD high in Myocardial infraction Hodgkin s lymphoma Megaloblastic anemia Hemolytic anemia

    10. Serum Bilirubin Bilirubin high in Hepatitis and liver malignancy Intra-hepatic and Extra-hepatic liver disease Pancreatic malignancy Hemolytic disease of the new born Hemolytic anemia Inherted disorder

    11. Serum Albumin Albumin measurement is useful in assessing the severity of liver disease

    18. Alcohol Metabolism Eric Niederhoffer SIU-SOM EtOH: ethanol ADH: alcohol dehydrogenase; genetic polymorphisms lower response to EtOH NAD+/NADH: nicotinamide adenine dinucleotide CAT: catalase MEOS: microsomal ethanol-oxidizing system P450: cytochrome P450 NADP+/NADPH: nicotinamide adenine dinucleotide phosphate AlDH: aldehyde dehydrogenase; ~50% ethnic Chinese lack gene Thiamine is consumed during hepatic metabolism of EtOH, hypothalamus responds to thiamine deficiency by ordering increase in hepatic ADH activity that gives enhanced EtOH degradation.EtOH: ethanol ADH: alcohol dehydrogenase; genetic polymorphisms lower response to EtOH NAD+/NADH: nicotinamide adenine dinucleotide CAT: catalase MEOS: microsomal ethanol-oxidizing system P450: cytochrome P450 NADP+/NADPH: nicotinamide adenine dinucleotide phosphate AlDH: aldehyde dehydrogenase; ~50% ethnic Chinese lack gene Thiamine is consumed during hepatic metabolism of EtOH, hypothalamus responds to thiamine deficiency by ordering increase in hepatic ADH activity that gives enhanced EtOH degradation.

    19. Pathway Perturbations Glc: glucose GK: glucokinase G6P: glucose-6-phosphate F6P: fructose-6-phosphate PFK: phosphofructokinase F16BP: fructose-1,6-bisphosphate PEP: phosphoenolpyruvate PK: pyruvate kinase Pyr: pyruvate PDH: pyruvate dehydrogenase Cit: citrate ICit: isocitrate IDH: isocitrate dehydrogenase aKG: a-ketoglutarate NAD+/NADH: nicotinamide adenine dinucleotide aKGDH: a-ketoglutarate dehydrogenase SCoA: succinyl coenzyme A Suc: succinate Fum: fumarate MDH: malate dehydrogenase OAA: oxaloacetate PC: pyruvate carboxylase LDH: lactate dehydrogenase PEPCK: phosphoenolpyruvate carboxykinase F16BPase: fructose-1,6-bisphosphatase G6Pase: glucose-6-phosphatase Ala: alanine Asp: aspartate ALT: alanine transaminase AST: aspartate transaminase Recall NADH/NAD+ controls PDH activity also through action of PDH kinase and phosphatase; PDH inhibition leads to increased [lactate], [pyruvate], [alanine].Glc: glucose GK: glucokinase G6P: glucose-6-phosphate F6P: fructose-6-phosphate PFK: phosphofructokinase F16BP: fructose-1,6-bisphosphate PEP: phosphoenolpyruvate PK: pyruvate kinase Pyr: pyruvate PDH: pyruvate dehydrogenase Cit: citrate ICit: isocitrate IDH: isocitrate dehydrogenase aKG: a-ketoglutarate NAD+/NADH: nicotinamide adenine dinucleotide aKGDH: a-ketoglutarate dehydrogenase SCoA: succinyl coenzyme A Suc: succinate Fum: fumarate MDH: malate dehydrogenase OAA: oxaloacetate PC: pyruvate carboxylase LDH: lactate dehydrogenase PEPCK: phosphoenolpyruvate carboxykinase F16BPase: fructose-1,6-bisphosphatase G6Pase: glucose-6-phosphatase Ala: alanine Asp: aspartate ALT: alanine transaminase AST: aspartate transaminase Recall NADH/NAD+ controls PDH activity also through action of PDH kinase and phosphatase; PDH inhibition leads to increased [lactate], [pyruvate], [alanine].

    20. Ketone Bodies Eric Niederhoffer SIU-SOM TAG: triacylglycerol HSL: hormone sensitive lipase FA: fatty acid Ile: isoleucine Leu: leucine; prominent source Lys: lysine Phe: phenylalanine Trp: tryptophan Tyr: tyrosine AT: aminotransferase aKA: a-ketoacid FA are bound to serum albumin and are transported through capillariesTAG: triacylglycerol HSL: hormone sensitive lipase FA: fatty acid Ile: isoleucine Leu: leucine; prominent source Lys: lysine Phe: phenylalanine Trp: tryptophan Tyr: tyrosine AT: aminotransferase aKA: a-ketoacid FA are bound to serum albumin and are transported through capillaries

    21. Ketogenesis TAG: triacylglycerol Acetyl CoA: acetyl coenzyme A Ile: isoleucine AACoAT: acetoacetyl coenzyme A thiolase AACoA: acetoacetyl coenzyme A Lys: lysine Trp: tryptophan HMGCoAS: 3-hydroxy-3-methylglutaryl coenzyme A synthase HMGCoA: 3-hydroxy-3-methylglutaryl coenzyme A Leu: leucine AA: acetoacetate Tyr: tyrosine Phe: phenylalanine 3HBDH: 3-hydroxybutyrate dehydrogenase 3HB: 3-hydroxybutyrate 3KACoAT: 3-ketoacyl coenzyme A transferase Inborn errors in HMGCoA synthase and HMGCoA lyase (increased [HMGCoA)TAG: triacylglycerol Acetyl CoA: acetyl coenzyme A Ile: isoleucine AACoAT: acetoacetyl coenzyme A thiolase AACoA: acetoacetyl coenzyme A Lys: lysine Trp: tryptophan HMGCoAS: 3-hydroxy-3-methylglutaryl coenzyme A synthase HMGCoA: 3-hydroxy-3-methylglutaryl coenzyme A Leu: leucine AA: acetoacetate Tyr: tyrosine Phe: phenylalanine 3HBDH: 3-hydroxybutyrate dehydrogenase 3HB: 3-hydroxybutyrate 3KACoAT: 3-ketoacyl coenzyme A transferase Inborn errors in HMGCoA synthase and HMGCoA lyase (increased [HMGCoA)

    22. Review Questions What are ketone bodies? How are ketone bodies generated (substrates, enzymes, pathways, location)? How are ketone bodies metabolized (enzymes, pathways, location)?

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