Ch04 b


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Ch04 b

  1. 1. Metabolism of the lipidsFatty acids have 4 major roles in the cell:  Building blocks of phospholipids and glycolipids Added onto proteins to create lipoproteins, which targets them to membrane locations Fuel molecules - source of ATP Fatty acid derivatives serve as hormones and intracellular messengers
  2. 2. Omega-3 f.acids shown toslow the development ofcardiovascular diseases
  3. 3.  The oxidation of f.acids – source of energy in the catabolism of lipids Both triacylglycerols and phosphoacylglycerols have f.acids as part of their covalently bonded structures The bond between the f.acids and the rest of the molecule can be hydrolyzed (as shown in the fig.) Fig. 21-1, p.569
  4. 4. p.569
  5. 5. Fig. 21-3, p.570
  6. 6. • Fatty acids oxidation begins with activation of the molecule.• A thioester bond is formed between carboxyl group of f.acid and the thiol group of coenzyme A (CoA-SH) (esterification reaction – in cytosol)
  7. 7. Fig. 21-5, p.571
  8. 8. When a f.acid with an even number of C atoms undergoes successive rounds of β-oxidation cycle, the product is acetyl- CoA.No. of molecules of acetyl-CoA produced = ½ the no. of C atoms in the original f.acid. (as shown in fig above)The acetyl-CoA enters the TCA cycle (the rest of oxidation to CO2 and H2O taking place via TCA cycle and ETC)β-oxidation takes place in mitochondria.
  9. 9. The oxidation ofunsaturatedf.acids does notgenerate as manyATPs as it wouldfor a saturatedf.acids (same Catoms) – thepresence ofdouble bond• the acyl-deH2asestep skipped –fewer FADH2 willbe produced
  10. 10. The catabolism of odd-carbon f.acids
  11. 11. Ketone bodiesSubstances related to acetone (“ketone bodies”) are produced when an excess of acetyl-CoA arises from β- oxidationOccurs because when there are not enough OAA to react with acetyl-CoA in TCA cycleWhen organisms has a high intake of lipids and low intake of CHO or starvation and diabetesThe reactions that result in ketone bodies start with the condensation of two molecules of acetyl-CoA to produce acetoacetyl-CoA
  12. 12. • the odor of acetone can be detected on thebreath of diabetics whose not controlled bysuitable treatment• Acetoacetate and β-hydroxybutyrate are acidic,their presence at high [ ] overwhelms thebuffering capacity of the blood• to lowered the blood pH is dealt by excretingH+ into the urine, accompanied by excretion ofNa +, K + and water → results in severedehydration and diabetic coma• synthesis of ketone bodies in liver mitochondria• transport ketone bodies in the bloodstream;water soluble• other organs such as heart muscle and renalcortex can use ketone bodies (acetoacetate) as thepreferred source of energy• even in brain, starvation conditions lead to theuse of acetoacetate for energy
  13. 13. FATTY ACID SYNTHESIS The anabolic reaction takes place in cytosol Important features of pathway: Intermediates are bound to sulfhydral groups of acyl carrier protein (ACP); intermediates of β-oxidation are bonded to CoA  Growing fatty acid chain is elongated by sequential addition of two- carbon units derived from acetyl CoA  Reducing power comes from NADPH; oxidants in β-oxidation are NAD+ and FAD  Elongation of fatty acid stops when palmitate (C 16) is formed; further elongation and insertion of double bonds carried out later by other enzymes
  14. 14. Pathway of palmitate synthesis from acetyl-CoA and malonyl-CoAThe biosynthesis off.acids involves thesuccessive addition oftwo-carbon units tothe growing chain.- Two of the three Catoms of the malonylgroup of malonyl-CoA are added to thegrowing fatty-acidchain with each cycleof the biosyntheticreaction
  15. 15. This reaction require multienzyme complex :fatty acid synthase Fig. 21-15c, p.583
  16. 16. Fig. 21-17, p.586
  17. 17.  Lipids are transported throughout the body as lipoproteins Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids and contain cell- targeting signals. Lipoproteins classified according to their densities:  chylomicrons - contain dietary triacylglycerols  chylomicron remnants - contain dietary cholesterol esters  very low density lipoproteins (VLDLs) - transport endogenous triacylglycerols, which are hydrolyzed by lipoprotein lipase at capillary surface  intermediate-density lipoproteins (IDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis and converted to LDLs  low-density lipoproteins (LDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis; major carrier of cholesterol in blood; regulates de novo cholesterol synthesis at level of target cell  high-density lipoproteins - contain endogenous cholesterol esters released from dying cells and membranes undergoing turnover