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BIOCHEMISTRY LECTURES. Figure 10-2 2. Stages in the extraction of energy from foodstuffs. Enzyme is inhibited by malonyl CoA! Why?. heart muscle kidney brain. 1. Synthesis takes place in the cytosol, in contrast with degradation, which occurs in the mitochondrial matrix.
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heart muscle kidney brain
1. Synthesis takes place in the cytosol, in contrast with degradation, which occurs in the mitochondrial matrix. 2. Intermediates in fattv acid synthesis are covalently linked to the sulf-hydryl groups of an acyl carrier protein (ACP), whereas intermediates in fatty acid breakdown are bonded to coenzyme A. 3. The enzymes of fatty acid synthesis in higher organisms are joined in a single polypeptide chain called fatty acid synthase. In contrast, the degradative enzymes do not seem to be associated. 4. The growing fatty acid chain is elongated by the sequential addition of two-carbon units derived from acetyl CoA. The activated donor of two-carbon units in the elongation step is malonyl-ACP. The elongation reaction is driven by the release of CO2. 5. The reductant in fatty acid synthesis is NADPH, whereas the oxidants in fatty acid degradation are NAD+ and FAD. 6. Elongation by the fatty acid synthase complex stops upon formation of palmitate (C16). Further elongation and the insertion of double bonds are carried out by enzyme systems of the endoplasmic reticulum with the fatty acyl groups as CoA derivatives.
Schematic diagram showing the proposed movement of the biotin prosthetic group from the site where it acquires a carboxyl group from HCO3- to the site where it donates this group to acetyl CoA.
Acetyl CoA carboxylase, which catalyzes the committed step in fatty acid synthesis, is a key control site.
Citrate transport system. The system achieves net transport of acetyl CoA from the mitochondrion to the cytosol and net conversion of cytosolic NADH to NADPH. Up to two molecules of ATP are expended for each round of the cyclic pathway.
All the carbons and all the hydrogens of fatty acids can have come from glucose. Know how.
To make prostaglandins and leucotrienes, animals use C20 fatty acids with 3,4 or 5 cis s in key positions. We must get fatty acids with s in positions w 6,9 or w 3,6,9 from plants.
18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 D CH3 w
Animals and plants place firstcis atD9 D 9 C16 D 9 C18
Animals and plants can place a subsequent Only plants can place a subsequent , separated , separated by –CH2– from an existing , towards the –COO- group, regardless of the length (C16, C18, C20) of the fatty acid. 6 new by –CH2– from an existing , towards the CH3– group. D 12 9 new existing D 9 existing
D C18:1 w C18:2 w C18:3 w C18:0 In plants 9 9 6 9 3 6 9
C18:2 w C18:3 w C20:3 w PGs1 C20:4 w PGs2 In animals or plants 6 9 6 9 12 6 9 12 6 9 12 15
C18:3 w3,6,9 C18:4 w3,6,9,12 C20:5 w3,6,9,12,15 w 3 6 9 12 15 PGs3
Important eicosanoids Vascular endothelial cells: vasdilatory inhibits platelet aggregation Platelets: aggregates platelets White blood cells, mast cells inflammatory, allergic
Aspirin COX
Structure of the active site of prostaglandin H2 synthase (COX)
Cyclooxygenases COX 1: constitutive - in plateletts - in gastrointestinal epithelial cells COX 2: induced in inflammatory process Selective inhibitors – non steroidal (NSAIDs) ? How do steroids reduce inflammation?