Metabolism of the lipids

Fatty acids have 4 major roles in the cell: Building blocks of phospholipids and

glycolipidsAdded onto proteins to create lipoproteins,

which targets them to membrane locationsFuel molecules - source of ATPFatty acid derivatives serve as hormones and

intracellular messengers

Omega-3 f.acids shown to slow the development of cardiovascular diseases

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

p.569

Fig. 21-3, p.570

• 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)

Fig. 21-5, p.571

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.

The oxidation of unsaturated f.acids does not generate as many ATPs as it would for a saturated f.acids (same C atoms) – the presence of double bond• the acyl-deH2ase step skipped – fewer FADH2 will be produced

The catabolism of odd-carbon f.acids

Ketone bodiesSubstances 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

• the odor of acetone can be detected on the breath of diabetics whose not controlled by suitable treatment• Acetoacetate and β-hydroxybutyrate are acidic, their presence at high [ ] overwhelms the buffering capacity of the blood• to lowered the blood pH is dealt by excreting H+ into the urine, accompanied by excretion of Na +, K + and water → results in severe dehydration 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 renal cortex can use ketone bodies (acetoacetate) as the preferred source of energy• even in brain, starvation conditions lead to the use of acetoacetate for energy

FATTY ACID SYNTHESIS

The anabolic reaction takes place in cytosolImportant 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 (C16) is formed; further elongation and insertion of double bonds carried out later by other enzymes

Pathway of palmitate synthesis from acetyl-CoA and malonyl-CoA

The biosynthesis of f.acids involves the successive addition of two-carbon units to the growing chain.- Two of the three C atoms of the malonyl group of malonyl-CoA are added to the growing fatty-acid chain with each cycle of the biosynthetic reaction

Fig. 21-15c, p.583

This reaction require multienzyme complex : fatty acid synthase

Fig. 21-17, p.586

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