FA Synthesis Flashcards
In humans, the ___ is the main site for FA synthesis
liver
note: other sites include: kidney, brain, lung, mammary gland, and adipose
The process of FA synthesis occurs in what part of the cell?
cytoplasm
FAs are synthesized from 2 carbon units (acetyl-CoA). ___ is the main source of the acetyl-CoA, with some contribution from ___
glucose; AAs
note: other cofactors/substrates include: NADPH, ATP, biotin, and HCO3-
The process of using acetyl CoA to produce FA in the cytosol requires two important enzymes. What are they?
- acetyl CoA carboxylase
2. FA synthase
When glucose is plentiful, glycolysis in the liver will produce “excess” ___ which enters mitochondria and produces ___-___ for the TCA cycle
pyruvate; acetyl-CoA
note: citrate, which is not further metabolized by the TCA can exit the mitochondria
In the cytosol, citrate is the substrate for ATP citrate lyase. What does this enzyme do? What does it require?
citrate is split back to oxaloacetate and acetyl-CoA
ATP is required
note: this enzyme is inducible
Cytosolic malate dehydrogenase reduces ___ to malate
OAA
What does the Malic enzyme do?
- converts malate to pyruvate
- produces NADPH which is necessary for FA synthesis
note: this enzyme is inducible
Acetyl-CoA carboxylase catalyzes the reaction producing ___-___ from acetyl-CoA
malonyl-CoA
Acetyl-CoA carboxylase requires ___ and is the rate-limiting enzyme of ___ ___
biotin; FA synthesis
Acetyl-CoA carboxylase is the regulated step of FA synthesis. It exists as either inactive ___ __ or as active ___.
proteomeric dimers; polymers
Acetyl-CoA carboxylase is stimulated by what? inhibited by what?
stimulated by citrate (feed forward)
inhibited by long-chain fatty acyl-CoA (feed back)
Acetyl-CoA carboxylase is also controlled by phosphorylation/dephosphorylation. True or false?
true
note: an AMP-dependent protein kinase phosphorylates the enzyme
Phosphorylation causes ___ of acetyl-CoA carboxylase?
inactivation
In regards to acetyl-CoA carboxylase, AMP would increase during times of ____
fasting
Glucagon stimulates the activity of the AMP-dependent kinase, which results in ___ of FA synthesis
inhibition
note: mechanism via cAMP-dependent protein kinase
A protein phosphatase dephosphorylates acetyl-CoA carboxylase. This causes ___ of the enzyme. This protein phosphatase is stimulated by ___
activation; insulin
Prolonged consumption of a diet containing excess calories results in increased synthesis of this enzyme
acetyl-CoA carboxylase
note: a low-calorie diet reduces synthesis of this diet
FA synthase is a multi-functional enzyme in eukaryotes. It is active as a ___. Each monomer contains ___ different enzymatic activities.
dimer; 7
FA synthase allows only one fatty acyl chain to be synthesized at a time. True or false?
false; two fatty acyl chains
FA synthase sequentially adds two-carbon units from ___-___ to a growing ___ ___ chain
malonyl-CoA; fatty acyl
The starting unit of FA synthase is ___-___ and the product is ____
acetyl-CoA; palmitate
- In the first round of the synthesis cycle, acetyl transacylase adds an acetyl group to the ___ of a cysteine residue of ketoacyl synthase domain of one monomer
SH
- Malonyl transacylase adds a malignly group to the SH of the ____-___ group of acyl carrier protein (ACP) domain of the other monomer
phospho-pantetheine
- 3-ketoacyl synthase catalyzes the FA synthase reaction adding the acetyl group to the malignly group and decarboxylation, leaving the product (a 3-ketoacyl group) bout the the ___ domain
ACP
- 3-ketoacyl reductase reduces the 3-keto group to an hydroxyl, using ___ as the reducing agent
NADPH
- The hydrates catalyzes the removal of H2O resulting in a ___-___ group
2-enoyl
- The enoyl reductase saturates the carbon-carbon double bond to produce a saturated acyl group (2 carbons longer) using ___ as the reducing agent
NADPH
- The lengthened acyl group is transferred from the ACP domain to the opposite monomers ____ ____ cysteine residue for another round
ketoacyl synthase
note: for each round, 2 carbons are added from malonyl-CoA
- A total of 7 rounds is completed to form a palmitoyl group. After the 7th round, the _____ hydrolyzes the palmitate from the ACP domain
thioesterase
In order to be further metabolized, the palmitate is converted to palmitoyl-CoA for what 4 things?
- esterfircation to triacylglycerols
- elongation
- desaturation
- esterfication to cholesteryl ester
Give the 2 steps of the overall equation for palmitate synthesis
- from acetyl-CoA and malonyl-CoA
2. from acetyl-CoA to palmitate - must account for ATP used by acetyl-CoA carboxylase
The major source of NADPH is the ___ ___ pathway with some provided by magic enzyme
pentose phosphate
FA elongation occurs primarily in the ____ ___
endoplasmic reticulum
The preferred substance of FA elongation is ____-___. The preferred product is ____-___
palmitoyl-CoA; stearoyl-CoA (18:0)
The formation of mono-unsaturated FAs begins with stearoyl-CoA desaturase which is an enzyme of the ER that requires what?
NADH or NADPH, molecular O2, cytochrome b5
In regards to stearoyl-CoA desaturase, the desaturation always occurs at carbon ___
9
The product of stearoyl-CoA denatures is what?
oleoyl-CoA or palmitoleoyl-CoA
Poly-unsaturated FAs have 2 important functions. What are they?
- increase membrane fluidity
2. source of important bio-active compounds (eicosanoids)
Formation of PUFAs depends on chain ____ and introduction of ___ bonds
elongation; double
Humans cannot introduce a double bond beyond carbon ___
9
FAs derived from oleic acid are referred to as w-9 or n-9. Why?
because the first double bond encountered rom the w or n carbon is 9 carbons toward the carboxyl carbon
Since humans cannot add double bonds beyond carbon 9, some FAs are required in the diet. Name 2 of these.
w-6 FA: linoleic acid is an essential FA
w-3 FA: alpha-linolenic acid is an essential FA
Synthesis of ____ acid is an example of synthesis of an important PUFA from an essential FA
arachidonic
