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Atip Likidlilid

CARBOHYDRATE METABOLISM. Atip Likidlilid. METABOLISM. Living organisms maintain complex order in dynamic steady state by importing food and energy from their surroundings. transformation of matter and energy to create complex molecules from simple ones by enzyme-catalyzed reactions .

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Atip Likidlilid

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  1. CARBOHYDRATE METABOLISM Atip Likidlilid

  2. METABOLISM • Living organisms maintain complex order in dynamic steady state by importing food and energy from their surroundings. • transformation of matter and energy to create complex molecules from simple ones by enzyme-catalyzed reactions

  3. METABOLIC PATHWAYS • series of consecutive enzymatic reactions that produce specific products • products of reactions metabolites End products (metabolic intermediates)

  4. Principal characteristics of metabolic pathways

  5. 1.Metabolic pathways are irreversible • highly exergonic • reactions go to completion

  6. A 1 2 Y X If cells require metabolite 2 1 2 turn on Independent control 2 1 turn off

  7. 2. Every metabolic pathway has a first committed step • irreversible ( exergonic ) reaction commits the intermediates down the pathway

  8. 3. All metabolic pathways are regulated • the first committed step is too slow to permit its substrate and product to equilibrate • most of other reactions in a pathway function close to equilibrium • committed step = rate-limiting step

  9. 4. Metabolic pathways in eukaryotic cells occur in specific cellular locations • biological membranes are selectively permeable to metabolites • specific transport protein

  10. Metabolic reaction mechanisms 1. group-transfer reactions 2. oxidations and reductions 3. eliminations , isomerization and rearrangements 4. reactions that make or break C-C bonds

  11. Metabolic categories • catabolism ( degradation ) • anabolism ( biosynthesis)

  12. complex metabolites 2- ADP + HPO 4 + NADP degradation biosynthesis NADPH ATP simple products

  13. CATABOLISM 1. digestion and absorption

  14. starchsucroselactosecellulose salivary amylase starch starch dextrin + glucose + maltose

  15. HCl stops action of amylase

  16. Pancreatic amylase starch dextrins + maltose + isomaltose

  17. mucosal cells(brush border) maltase , lactase , invertase , isomaltase , dextrinase glucose , fructose , galactose Portal circulation liver cellulose

  18. galactose , frutose from portal circulation glucose Glucose in systemic circulation peripheral tissue

  19. Transport of monosaccherides into tissues • 1. Na+ - dependent glucose transport Phlorhizin (plant glycoside) - inhibitor • 2. Facilitated glucose transport Cytochalasin (from mold) – inhibitor (GLUT5)

  20. Transporter Tissue distribution 1. Sodium-dependent unidirectional transporter SGLT 1 (ใช้พลังงาน) small intestine,kidney 2. Facilitated bidirectional transporters GLUT1 red cells,blood brain barrier,kidney,colon GLUT2 liver,pancreatic B-cells,small intestine GLUT3 neuron,placenta,testes GLUT4 fat,skeletal muscle,heart (ใช้ insulin) GLUT5 small intestine,testes (fructose uptake)

  21. Glycolysis (Pasteur effect) • anaerobic glycolysis (oxygen debt) glucose lactate • aerobic glycolysis (oxygen load) glucose pyruvate

  22. Pathway of glycolysis (cytosol) Stage 1 : formation of glucose 6 - P

  23. hexose (fructose,galactose) hexokinase glucose hexose 6- P glycogen ATP phosphorylase hexokinase Pi isomerase ADP glucose 1- glucose 6- P P phosphoglucomutase glycolysis

  24. Stage 2 : split G-6- P 2 Triose- P

  25. G-6- P Phosphohexose isomerase Fructose-6- P ATP * Phosphofructokinase-1 ADP Fructose-1,6-bis P Aldolase Dihydroxyacetone phosphate (DHAP) (95%) Glyceraldehyde- 3- P Triose- P -isomerase

  26. Stage 3:Glyceraldehyde-3- P Pyruvate

  27. Gly-3- P Pi + NAD + Gly-3- P dehydrogenase NADH+H + 1,3-bis P - glycerate aerobic O2 via cytochrome ADP Phosphoglycerate kinase * ATP 3- P - glycerate Phosphoglycerate mutase 2- P - glycerate Enolase H2O

  28. 2- P - enolpyruvate ADP Pyruvate kinase * ATP (couple reaction) 2- enolpyruvate Pyruvate kinase pyruvate NADH+H+ Lactate dehydrogenase NAD+ lactate (anaerobic) * substrate level phosphorylation

  29. Energetics of glycolysis ATP/mole of glucose glycolysis anaerobic aerobic 1. hexokinase -1 -1 2. phosphofructokinase-1 -1 -1 3. phosphoglycerate kinase +2 +2 4. pyruvate kinase +2 +2 - +4 (+6) 5. 2 (NADH.H+ NAD+) total +2 +6(+8)

  30. Inhibitors in glycolysis

  31. 1. glyceraldehyde-3- P dehydrogenase • 1.1 Iodoacetate (ICH2COO-) • SH group of cysteine residue in active site of the enzyme by covalent bond • 1.2 Arsenate (AsO43-) (uncoupler) • competitve inhibitor of Pi • uncouple oxidation and phosphorylation 2. enolase: required Mg2+ for activity • Fluoride (F-) forms tightly bound complex with Mg2+ at the active site

  32. Regulation of glycolysis • 3 allosteric enzymes • catalyzed non equilibrium reactions

  33. Enzymes Inhibitors Activators - HK G-6- P PFK-1* ATP,citrate,PEP ADP,AMP, cAMP (by insulin), FBP (F-2,6- P ) F-6- P , NH4+, Pi ( rate limiting enzyme ) PK ATP , alanine , fatty acid,acetyl CoA FBP

  34. Oxidation of pyruvate to acetyl Co A • pyruvate transporter (mitochondria) • pyruvate dehydrogenase complex • pyruvate dehydrogenase ( E1) ( TPP ) • dihydrolipoamide acetyltransferase ( E2 ) ( lipoic acid ) • dihydrolipoamide reductase ( E3 ) ( FAD , NAD )

  35. TPP pyruvate + NAD+ + Co A Acetyl Co A + NADH.H+ + CO2

  36. Regulation of pyruvate dehydrogenase complex 1. Control by product inhibitor - NADH , acetyl Co A และ ATP 2. Comtrol by product activator - pyruvate, ADP, Ca2+

  37. Inhibitors of PDH complex • arsenite ( AsO2- ) and Hg2+ (mercuric ion ) complex -SH of E2 • lactic acidosis • neurologic disturbances

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