Ch04
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Transcript of Ch04
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