Section 7. Lipid Metabolism

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Section 7. Lipid Metabolism

• Membrane lipids

11/08/05
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Some Control Sites of Fatty Acid Metabolism
Synthesis increased by ATP, NADH, acetyl CoA,
citrate, insulin and malonyl CoA.
Oxidation increased by AMP, palmitoyl CoA,
glucagon and epinephrine.
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Essential Fatty Acids

• linoleate C182 ??9??12
• linolenate C183 ??9?12?15
• arachidonate C204 ??5??8?11?14
• eicosapentaenoate C205 ??5??8?11?14?17
• These polyunsaturated fatty acids (also called
  w-fatty acids) are precursors of eicosanoid
  hormones.
• Humans lack the enzymes needed to introduce
  double bonds beyond the 9-position.

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Biosynthesis of Eicosanoid Hormones
Fig. 22.30

• These families of signal molecules include a
  variety of structures and have varied localized
  effects.
• They modulate inflammation, hemostasis, ion
  transport, synaptic transmission and sleep.

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Selected Eicosanoid Hormone Structures

• Synthesized intracellularly, starting with
  arachidonic acid.
• Bind 7TM receptors of nearby cells.

Fig. 22.31
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Platelet Aggregation

• Marine and terrestrial fatty acids produce
  slightly different products.
• Blood platelet aggregation is sensitive to these
  differences.
• A2 activates
• A3 does not.
• I2 and I3 inhibit.

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Aspirin Anti-Inflammatory Mechanism
Fig.12.25

• Aspirin acetylates serine 530 in a tunnel
  leading to the active site of prostaglandin
  synthetase, which blocks arachidonate binding.
• Fewer prostaglandins and prostacyclins made.
• This also reduces thromboxane production which
  makes asprin antithrombic, as well as
  anti-inflammatory.

Fig.12.22
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Prostaglandin H2 Synthase-1

• Membrane bound

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Membrane Lipids

• Hydrophobic enough to be insoluble in water with
  highly localized hydrophilic portion.
• Examples are
• Phosphoglycerides??
• ??Sphingolipids
• Cholesterol (not shown) is also common in
  membranes.

Stryer 4th
Stryer 4th
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Lipid Bilayers

• Phosphoglycerides and sphingolipids have two
  non-polar alkyl chains and a polar head group.
• These amphipathic structures spontaneously form
  sheet-like bilayer structures in aqueous
  solutions.
• The polar head groups face the water.
• The non-polar tails are not in contact with the
  water.

Fig. 12.8
Fig. 12.10
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Phosphoglyceride Structure

• The structure of the alcohol moiety, attached by
  a phosphoester bond, is variable.

Fig. 12.3
(p 323)
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Phosphoglyceride Biosynthesis

• CDP-diacylglycerol is an activated intermediate
  for several phosphoglycerides.
• Phosphatidate is also the precursor for
  triacylglycerol.

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Biosynthesis of Sphingolipids (I)

• First the palmitoyl chain is extended.
• Then it is reduced.

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Biosynthesis of Sphingolipids (2)
Fig. 26.3

• A second acyl group is attached.
• A variety of polar head groups are added (see
  next slide).

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Sphingolipids
Fig. 26.3
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Gangliosides
Fig. 26.4

• Gangliosides have at least one acidic sugar.
• Are prevalent in neural tissue.
• The number and structures of the sugars vary.
• Tay-Sachs disease is due to ?-N-acetylhexosamidase
  deficiency, which inhibits ganglioside turnover.

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(p 722)
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Membrane Structure
Fig. 12.17

• Lipid bilayer provides membranes impermeability
  to polar solutes.
• Proteins determine membrane function.
• Channels, carriers, receptors, signal
  transducers, pumps.

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Amphipathic Molecules in Water

• Oils (left) are too hydrophobic to be
  significantly soluble in water. They form
  monolayers at the water air surface.

Stryer 4th

• Bilayers (see above) are formed by less
  hydrophobic, but amphipathic, structures.
  Typically they have two acyl chains.

• Structures with one acyl chain (right), such as
  fatty acids and some detergents, form micelles.
  Examples of micelle function are fat uptake (in
  vivo) and protein isolation (in vitro).

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Fig. 12.9
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Vesicles

• Vesicles are small spherical bilayer
  structures.
• They are produced in vivo and in vitro.

Fig. 12.12

• Dentin matrix vesicles have a role in dentin
  formation.
• Acetyl choline release is via vesicles.
• Membranes are isolated as vesicles for
  experimental study.
• Targeted drug and gene delivery by vesicles is
  being developed.

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Detergents

• Water soluble, with substantial hydrophobic
  portions.
• Binds to hydrophobic portions of other molecules
  and makes them soluble in water.
• Bile salts and soaps are detergents.
• Chlorhexidine is strong enough to solubilize oral
  bacterial membranes.
• Other detergents are gentle enough to solubilize
  membrane enzymes without denaturation.

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• Web links
• Lipids and Membranes. A web page reviewing the
  topic.
• Next topic Steroids