Biochemistry of the liver

1. Biochemistry of the liver Vladimíra Kvasnicová

2. The figure was adopted from http://faculty.washington.edu/kepeter/119/images/liver_lobule_figure.jpg (April 2007)

3. The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_003.jpg (April 2007)

4. The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2

5. Central position in energy and intermediary metabolism • regulation of blood concentration of many metabolites • regulation of storage and production of energy • synthesis of molecules for other tissues • interconversion of nutrients • storage of some substances • formation and secretion of bile

6. Glucose in the liver can be • transformed to fatty acids • stored in glycogen molecules • oxidized to acetyl-CoA • used for production of NADPH

7. Metabolism of saccharides • glucostatic function of the liver • glycogen synthesis, glycolysis • glycogendegradation, gluconeogenesis • glucokinase, glc-6-phosphatase • pentose cycle • Cori cycle and glucose-alanine cycle

8. Metabolism of saccharides (II) • excess of glucose FFA TAG • transformation of saccharides to glucose • metabolism of fructose (fructokinase) • synthesis of amino saccharides • synthesis of uronic acids • degradation of insulin and glucagon

9. The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_004.jpg (April 2007)

10. Fatty acids entering the liver can be • used for synthesis of TAG • transformed to glucose • transformed to ketone bodies • oxidized to CO2 and H2O

11. Metabolism of lipids • liver controls blood FFA concentration • energy is produced mainly by -oxidation • synthesis of ketone bodies • synthesis of TAG (from FFA, glc, AA) • synthesis of cholesterol • synthesis of bile acids • synthesis of phospholipids • synthesis of VLDL and HDL • degradation of plasma lipoproteins

12. The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2

13. The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_006.jpg (April 2007)

14. Choose the correct statement(s) about the metabolism of lipoproteins in the liver: • the hepatocyte synthesizes chylomicron particles • triacylglycerols leave the liver incomporated in VLDL • apoproteins are synthesized in the liver • LDL transports cholesterol from peripheral tissues to the liver

15. Amino acids in the liver can be • used for synthesis of clotting factors • used for synthesis of immunoglobulins • transformed to glucose (only glucogenic amino acids) • decomposed, urea is one of the main products

16. Metabolism of N-containing compounds • synthesis of plasma proteins(except Ig) • synthesis of coagulation factors • synthesis of acute phase reactants • degradation of amino „N“ (urea, Gln) • synthesis of nonessential amino acids • metabolism of aromatic AAs • degradation of purines to uric acid • synthesis of creatine • conjugation and excretion of bilirubin

17. The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_005.jpg (April 2007)

18. Bilirubin • belongs among linear tetrapyrrols • is excreted mainly with bile • is soluble in water after itsconjugation, e.g. with glucuronic acid • is called „direct bilirubin“ if it is bound to albumin

19. The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2

20. excretion The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_007.jpg (April 2007)

21. Causes of hyperbilirubinemia 1) increased bilirubin formation 2) decreased bilirubin uptake by hepatocyte 3) deficit in conjugation 4) defect of active transport to bile 5) biliary obstruction The figure was adopted from the book: Klinická biochemie - požadování a hodnocení BCH vyšetření /J. Masopust (Karolinum 1998)

22. indirect = unconjugated = insoluble in water (= fat soluble) = bound to albumin direct = conjugated = soluble in water

23. Metabolism of vitamins • provitamins vitamins, storage of vitamins • carotenes vitamin A • 25-hydroxylation of provitamin D (→ calcidiol) • cleavage of side chain of vitamin K • storage of vitamin B12 • synthesis of nicotinic acid from Trp • formation of coenzymes from B vitamins

24. Metabolism of minerals • storage of iron (ferritin) • storage and metabolism of other trace elements(Cu, Mn, Co, Mo, Zn,..) • synthesis of transport proteins (transferrin, ceruloplasmin) • deiodation of thyroidal hormones → I- (iodide)

25. Metabolism of hormones • degradation and excretion (see 3rd semester) Metabolism of xenobiotics • see next seminar

26. Metabolic pathways in different zones of the liver lobule The figure was adopted from http://www.tharu.com/academic/html/newcastle/liver.htm (April 2007)

27. a) periportal hepatocytes - higher pO2: • more mitochondria, less ER • blood contains a lot of O2 and nutriens • more of oxidative reactions • antioxidative defense (glutathion) • CC, RCH, oxidative phosphoryl., -oxidation • urea synthesis • glukoneogenesis • cholesterol synthesis • proteosynthesis

28. b) perivenous hepatocytes - lower pO2: • blood contains few O2 and nutriens • more of reductive reactions • synthesis of lipids • glycogen synthesis • ketogenesis • biotransformation of xenobiotics (sm. ER) • detoxification of NH3: synthesis of Gln

29. Glutamine cyclein the liver The figure was adopted from: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

30. Choose the mtb pathway(s) proceeding only in the liver: • gluconeogenesis • ketogenesis • synthesis of urea • synthesis of bile acids

31. Choose correct statement(s) about enzymes of hepatocytes • ALT participates in a metabolismof amino acids • ALP belongs among esterases • LD needs NADH as a coenzyme • AST catalyzes one of reactionsof a pentose cycle

32. Liver tests • total bilirubin (‹ 22 M) • ALT(‹ 0,75 kat/L) • AST (‹ 0,75 kat/L) • ALP (‹ 2,29 kat/L) • GMT (men: 0,25-1,77, women: 0,17-1,10 kat/L) the values are used in FNKV