Ch 23 - Biosynthesis of Fatty acids & eicosanoids Flashcards
Fatty acids are synthesized by an ______________, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the CYTOSOL.
extramitochondrial system
In most mammals, __________ is the primary substrate for lipogenesis, but in ruminants it is __________, the main fuel molecule they obtain from the diet.
Glucose
Acetate
However, inhibition of lipogenesis occurs in _______________, and variations in the activity of the process affect the nature and extent of _________.
type 1 (insulin-dependent) diabetes mellitus
Obesity
______________ in phospholipids of the cell membrane are important in maintaining membrane fluidity.
Unsaturated fatty acid
A high ratio of ______________ in the diet is considered to be beneficial in preventing coronary heart disease.
polyunsaturated fatty acids to saturated fatty acids (P:S ratio)
______________ mediate inflammation, pain, and induce sleep and also reg-ulate blood coagulation and reproduction.
Prostaglandins
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as __________ and _________ act by inhibiting prostaglandin synthesis.
aspirin and ibuprofen
_______________ have muscle contractant and chemotactic properties and are important in allergic reactions and inflammation.
Leukotrienes
THE MAIN PATHWAY FOR DE NOVO SYNTHESIS OF FATTY ACIDS (LIPOGENESIS) OCCURS IN THE ______________.
CYTOSOL
This system is present in many tissues, including liver, kidney, brain, lung, mammary gland, and adipose tissue. Its cofactor requirements include:
- NADPH
- ATP
- Mn2+
- biotin
- HCO3 (as a source of CO2)
_____________ is the immediate substrate, and ____________ is the end product.
Acetyl-CoA
free palmitate
production of ____________ is the Initial & Controlling Step in Fatty acid Synthesis
Malonyl-Coa
_____________ as a source of CO2 is required in the initial reaction for the carboxylation of acetyl-CoA to malonyl-CoA in the presence of ATP and ________________.
Bicarbonate
acetyl-CoA carboxylase
This enzyme has a major role in the regulation of fatty acid synthesis.
Acetyl-CoA carboxylase
_______________ has a requirement for the B vitamin biotin and is a multienzyme protein containing biotin, biotin carboxylase, biotin carboxyl carrier protein, and a carboxyl transferase, as well as a regulatory allosteric site.
Acetyl-CoA carboxylase
The _______________ Is a homodimer of Two polypeptide Chains Containing Six Enzyme activities.
Fatty acid Synthase Complex
After the formation of malonyl-CoA, fatty acids are formed by the _______________.
fatty acid synthase enzyme complex
The individual enzymes required for fatty acid synthesis are linked in this multienzyme polypeptide complex that incorporates the _______________, which has a similar function to CoA in the β-oxidation pathway. It contains the vitamin ____________ in the form of 4′-phosphopantetheine.
acyl carrier protein (ACP)
pantothenic acid
X-ray crystallography of the three-dimensional structure, however, has shown that the complex is a __________, with two identical subunits, each containing 6 enzymes and an ACP, arranged in an ___________.
homodimer
X shape
The position of the ACP and thioesterase domains cannot be resolved as yet by x-ray crystallography, possibly because they are too __________, but they are thought to lie close to the _______________ enzyme.
Flexible
3-ketoacylreductase
The use of one _________________ has the advantages of achieving the effect of compartmentalization of the process within the cell without the erection of permeability barriers, and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene.
multienzyme functional unit
Initially, a priming molecule of acetyl-CoA combines with a ______________ while malonyl-CoA combines with the adjacent ´SH on the _________________ of ACP of the other monomer.
cysteine ‘SH group
4′-phosphopantetheine
These reactions are catalyzed by _____________, to form acetyl (acyl)-malonyl enzyme.
malonyl acetyl transacylase
The acetyl group attacks the methylene group of the malonyl residue, catalyzed by ________________, and liberates CO2, forming 3-ketoacyl enzyme (acetoacetyl enzyme) (reaction 2), freeing the cysteine —SH group.
3-ketoacyl synthase
_______________ allows the reaction to go to completion, pulling the whole sequence of reactions in the forward direction.
Decarboxylation
The 3-ketoacyl group is reduced, dehydrated, and reduced again (reactions 3-5) to form the corresponding _____________.
saturated acyl-S-enzyme.
The sequence of reactions is repeated six more times until a saturated _________________ has been assembled.
16-carbon acyl radical (palmitoyl)
It is liberated from the enzyme complex by the activity of the sixth enzyme in the complex, _______________.
thioesterase (deacylase)
The free palmitate must be activated to ___________ before it can proceed via any other metabolic pathway
acyl-CoA
In mammary gland, there is a separate thioesterase specific for acyl residues of ______________, which are subsequently found in milk lipids.
C8, C10, or C12
The acetyl-CoA used as a primer forms carbon atoms ____ and ____ of palmitate.
15 and 16
The addition of all the subsequent C2 units is via __________.
malonyl-CoA
_____________ acts as primer for the synthesis of long-chain fatty acids having an odd number of carbon atoms, found particularly in ruminant fat and milk.
Propionyl CoA
The Main Source of NADPH for Lipogenesis Is the _____________.
pentose phosphate pathway
________ is involved as a donor of reducing equivalents in both the reduction of the 3-ketoacyl and of the 2,3-unsaturated acyl derivatives.
NADPH
The oxidative reactions of the pentose phosphate pathway are the chief source of the ___________ required for the reductive synthesis of fatty acids.
hydrogen