Chapter 4

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

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

Fig. 21-2, 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

Fig. 21-6, p.572

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 energy released by the oxidation of acetyl-CoA formed by β-oxidation of f.acids can be used to produce ATP.

There are two sources of ATP: Reoxidation of the NADH and FADH2 produced by β-oxidation ATP production from processing acetyl-CoA via TCA cycle and

oxidative phosphorylation

NADH and FADH2 produced by β-oxidation and TCA cycle enter ETC and ATP produced through oxidative phosphorylation

Table 21-1, p.575

32 moles of ATP produced from complete oxidation of CHO (but, glucose is 6C atoms, so 6 x 3 = 18 C atoms. Therefore, 32 x 3 = 96 ATP.

e.g stearic acid: 18 C atoms = produced 120 moles of ATP

Reason? F.acid is all

hydrocarbon except carboxyl group – exists in highly reduced state

H2O is produced in oxidation of f.acids – can be a source of water for organisms that live in desert

Lipids

p.575a

Camel

Kangaroo rats

Fig. 21-8, p.576

The catabolism of odd-carbon f.acids

The catabolism of unsaturated f.acids

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

Fig. 21-9b, p.577

Fig. 21-10a, p.578

Fig. 21-10b, p.578

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

• 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

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

Fig. 21-12, p.581

Step 1

Fig. 21-13, p.581

Step 2

Fig. 21-14b, p.582

Malonyl-CoA inhibits carnitine

acyltransferase I

Fig. 21-15, p.583

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. 21-15a, p.583

Fig. 21-15b, p.583

Step 3

Fig. 21-15c, p.583

Step 4

This reaction require multienzyme complex : fatty acid synthase

Fig. 21-16, p.584

Table 21-2, p.586

There are several additional reactions required for the elongation of f.acid chain and the introduction of double bonds. When mammals produce f.acids with longer chains than that of palmitate, the reaction does not involve cytosolic f-acid synthase.

There are two sites for chain lengthening reactions: ER (endoplasmic reticulum) and mitochondrion.

Fig. 21-17, p.586

Table 21-3, p.599

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