BIOCHEMISTRY LECTURES

Figure 10-2 2

Stages in the extraction of energy from foodstuffs.

Enzyme is inhibited by malonyl CoA!

Why?

heartmusclekidneybrain

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.

positions 6,9 or 3,6,9 from plants. We must get fatty acids

withs in

To make prostaglandins and leucotrienes, animals useC20 fatty acids with 3,4 or 5 cis s in key positions.

CH3

1 2 43 5 6 7 8 9 10 11 12 13 14 15 16 17 18

18 17 1516 14 13 12 11 10 9 8 7 6 5 4 3 2 1

C16

9

Animals and plants place first cis at 9

9

C18

6

new

9

by –CH2– from an existing , towards the –COO- group,regardless of the length (C16, C18, C20) of the fatty acid.

Animals and plants can place a subsequent , separated

existing

9

by –CH2– from an existing , towards the CH3– group.Only plants can place a subsequent , separated

existing

12

new

9

9

9

9

6

3 6

In plants C18:0

C18:1

C18:2

C18:3

In animals or plants

6 9 12 15

6 9 12

6 9 12

6 9

PGs1

PGs2

C18:2

C18:3

C20:3

C20:4

C18:3 3,6,9 C18:4 3,6,9,12 C20:5 3,6,9,12,15

3 6 9 12 15PGs3

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?

N-Acetylneuraminate

All the carbons and hydrogens can have come from glucose.

Additional liver enzyme