38 Fatty Acid Synthesis Flashcards
what is the storage mechanism for excess glucose?
lipid biosynthesis
what structure is the major site for lipid biosynthesis?
the liver to care for its membrane and exported out into the blood to the adipose to be stored and this is done under an insulin signal; remember that fats are oxidized under glucagon and they are formed during insulin
where are the FAs synthesized?
in the cytosol
what provides the reducing equivalents in FA synthesis?
NADPH
what is the starting material for FA synthesis?
acetyl CoA
How are the FAs synthesized? meaning through the addition of this incrementally?
by the incremental addition of 2 carbon units from acetyl CoA leading to the predominance of even numbered FA chains
since we know that acetyl CoA is the starting material for FA synthesis and that it begins in the cytosol, how can this happen?
Acetyl CoA is formed in the mitochondrial matrix but cannot cross the inner mitochondrial membrane
Acetyl CoA condenses with oxaloacetate (OAA) to form citrate (first reaction of the TCA cycle)
Citrate is transported out of the mitochondrion
where is acetyl CoA formed again?
in the mitochondrial matrix but cannot cross the inner mitochondrial membrane
what converts pyruvate to acetyl CoA under normal conditions?
pyruvate dehydrogenase
what converts pyruvate to OAA under normal conditions?
pyruvate carboxylase and used more frequently when Acetyl CoA is being produced more and citrate is produced and if liver is okay on energy then TCA activity is halted and citrate builds up and so it can leave become cleaved by citrate lyase to produce acetyl CoA
what is the number one user for carbs?
the brain
in terms of the TCA, is OAA favored or less favored?
less favored because there is a malate OAA that has a positive delta G that favors malate and so less OAA under times when the TCA cycle is not running very fast and this is why pyruvate carboxylase is important
what enzyme is necessary for fat/cholesterol synthesis?
citrate lyase
what are the two pathways where NADPH is produced?
in the PPP and conversion of malate to pyruvate
what is the first enzyme of the PPP?
G-6-P dehydrogenase
why is malic enzyme important to note?
Malic enzyme is a key enzyme to have on the “need to know list. If a patient has a problem with NADPH production (Pentose Phosphate pathway), malic enzyme is also a producer of NADPH and can help make up for that deficiency – in liver.
what is the function of Malonyl CoA?
primarily for FA synthesis, so once here the pathway is committed to FA synthesis
what is palmitate derived from in relation to fatty acid synthase complex?
malonyl CoA to a growing acyl chain
what is fatty acid synthase?
a single multifunctional protein with 7 different enzyme activities in a single polypeptide chain which forms a homodimer
what protein cofactor is also needed for the fatty acid synthase complex?
Acyl Carrier Protein (ACP) which contains phosphopantetheine, a prosthetic group very similar to coenzyme A
in the fatty acid synthase complex, where does the malonyl CoA attach?
to the -SH on ACP
what are the 5 stages in FA synthesis?
loading condensation reduction dehydration reduction
what does the ACP (Acyl Carrier Protein) do?
it carries the Acyl for the fat
T/F, fatty acid synthesis requires Malonyl CoA?
true
two main takeaways for FA synthesis?
loading phase through acetyl CoA and then Malonyl CoA used for elongation
why is NADPH a critical factor in fatty acid biosynthesis? or what would happen if it is deficient and its effect on fatty acid biosynthesis
trouble making fat
trouble with membranes
trouble with adipose storage
how many times does the FA synthesis cycle continue?
this cycle is repeated 7 times forming palmitate (16 carbon chain) which uses malonyl ACP each time
in the final reaction of the FA synthesis what happens?
you have the cleavage of palmitoyl ACP by a thioesterase to release the free fatty acid and so palmitate is rapidly converted to palmitoyl CoA by acyl CoA synthetase
in terms of elongation of fatty acids besides palmitate like stearate (C18:0) and oleate (18:1) how and where does this happen?
The elongation and desaturation enzymes are localized to the cytoplasmic face of the endoplasmic reticulum
The elongase uses fatty acyl CoA as substrate and extends the chain two carbons at a time using malonyl CoA condensation followed by reduction, dehydration and reduction using NADPH in analogous fashion to FA synthase.
since human desaturates can not introduce double bonds in a saturated fat past carbon 10 what positions can they saturated at?
C5, C6 and C9 examples being palmitic acid to palmitoleic acid (16:1, Δ9) and stearic acid to oleic acid (18:1, Δ9)
what are the limitations to where humans cannot place double bonds?
between carbon 10 and the ω-carbon (terminal methyl group)
what is an important precursor for the production of arachidonic acid?
linoleic acid and so this can be modified through use of desaturase and elongation to produce the arachidonic acid
