Download Dominant Dietary Fatty Acids

Kin 217 - November 14th
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Slide on Dominant Dietary Fatty Acids
Peroxisome – 20 C fatty acids that don’t enter mitochondrial oxidation…18 C can
enter it
o In times of need, structural (long) can be β-oxidized (shortened down) and
shunted to break down to get energy (?)
Mechanism of fat synthesis
o Conversion to fat
 Excess carbohydrate after glycogen filled
 Ethanol and some amino acids
General principles
o Fatty acids
 Synthesized from acetyl-CoA (2 Carbons)
 Fatty acids tend to have even numbers of carbon atoms
o Carbohydrates
 Pyruvate
 Acetyl-CoA
o Some bacteria and plants
 Can make glucose from acetyl-CoA (ch 15)
 One of the reason you can’t find a lot of fat in plants
Synthesis of malonyl-CoA
o Acetyl-CoA
 Lacks energy to drive fatty acid syntheis
 WHY do we do this?
 Acetyl-CoA has very low energy
 Need energy to drive fatty acid synthesis
 Need energy into Acetyl-CoA…equivalent to using a Red
Bull shot so that reaction that occurs is irreversibly
Diagram on Malonyl CoA synthesis
o Good old biotin is involved
 Can use carbonate to add CO2 group
Malonyl-CoA
o (2 carbons plus 1 carbon)
o Acetyl-CoA plus a CO2
o Supplies 2-Carbons t fatty acid synthase
 Lose a CO2 immediately
 WHY? (it seems stupid that we gain a carbon just to lose 2..)
 Need a thermodynamically irreversible reaction
Fatty Acid Synthase
o Text ignores details
 Focus on:
 Acyl-carrier protein (ACP)
 β-ketoacyl synthase (has thiol group  sulphur-hydrogen
group)
 Ignores:
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Dimer (do you remember what this is? TWO identical
subunits linked together)
 7 catalytic sites + acyl-carrier protein (ACP)
 Mentions:
 Bacteria have separate enzymes
 Animas have a enzyme complex
Structure of fatty acid synthase (diagram)
o Top half is one unit, bottom is the other unit (dimmer)
Acyl carrier protein (ACP)
o β-oxidation
 CoA is the carrier
o Fatty acid synthesis
 Acyl group carrier is ACP
 Contains part of the CoA molecule
 Homology in acyl carrier group and CoA molecule (?)
Acetyl CoA slide…
Fig 14.1
o Priming reaction at first
Reactions catalyzed by fatty acid synthase (Diagram)
o Two business enzymes
o Ying-yang…fully activated at both ends of enzymes
o Why would mammals benefit from 7 sites?
 Tends to be a little more efficient
 The players are all together, substrate there
Fig 14.2
o The 3 steps missing from the cycle
The reductive steps in fatty acid synthesis
o The reductant is NADPH rather than NADH!
o Difference between NADPH and NADH?
 Extra phosphate group on NADPH
What is NADP+?
o Extra phosphate
 Identification signal
 Reductive power for energy use
 Reductive power for synthesis
o NAD+ and NADP+ reduction occur using separate mechanisms
 Compartmentalization
Where does fatty acid synthesis take place?
o Fatty acids synthesis to palmitate
 Cytosol
o Acetyl-CoA formed in mitochondria
 Restrictions on getting mitchondria into cytosol for fatty acid
synthesis (?)
Fig 12.10
o What enzyme?
 Pyruvate dehydrogenase
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Making acetyl-CoA inside mitochondria
Fig 14.4
o How do we get acetyl-CoA outside mitochondria?
o Form citrate with Citrate synthase that can be shunted outside
mitochondria
 Need ATP to break down citrate to make acetyl-CoA
 Not a bad thing of having to use ATP when we have a situation of
excess storage/energy (?)
o Pyruvate can re-enter mitchondria
o Somehow, we need to make NADPH
 Oxaloacetate back to pyruvate
 Sacrificing NADH to form NADPH (?)
Fig 14.3
Metabolism of pyruvate
o Pyruvate carboxylase reaction
o Topping up mechanism(?)
NADPH
o NADPH from “malic enzyme”
 ½ reducing power required for fatty acid synthesis
 Other ½ form pentose phosphate pathway (ch 17)
o Linked to excess glucose supply (NADPH will be more abundant when
energy supply is abundant)
Unsaturated Fatty Acid Synthesis
o Acetyl-CoA  16:0 (fairly important fatty acids)
 How do we get other fatty acids?
 Elongase reaction (gain 2 to get 18:0)
 Desaturases..
 ∆9 Desaturase can add double bond into saturated fatty acid
length to give 18:1n-9 (something about alpha and omega
ends????)
 How do we make polyunsaturated fatty acids?
 Need a ∆12 desaturase…add double bond 12 carbons from
alpha end…6 from the omega end
 ∆12 and ∆15 don’t occur in mammals (only in plants and
bacteria)…
 Where do we get it then?
 DIET!
 We can’t synthesize 18:2n-6 and 19:3n-3
 We can make 16:1n-7…
PUFA Biosynthesis
o Once we make 18:2n-6, we can add or take away carbons from 18C
precursor
o But humans depend on getting longer fats from the diet…
o Cats lack ∆5 Desaturase
 Carnivores don’t need to synthesize long fatty acids because
they’re eating a lot of meat (?)
o 18:2, 18:3, essential fatty acids! WE can synthesize everything else…dry
skin is a first sign of fatty acid deficiency
 If we don’t have these 2 in our diet, 18:2n9 can enter and be
worked on by to get a 23n9 (?)…
 Peroxisome – remember all fatty acids attached to a CoA group