Chapter 28 Flashcards
Fatty Acid Synthesis Occurs in 3 Stages
- Transfer of acetyl-CoA out of mitochondria (where its produced) and into the cytoplasm (site of synthesis)
- Acetyl-CoA is transported in the form of citrate, which is cleaved (split) to yield acetyl-CoA and oxaloacetate - Fatty acid synthesis begins in cytoplasm w/ activation of acetyl-CoA (2-step reaction) to form malonyl-CoA
- Fatty acid is synthesized, 2 carbons at a time (repetitive addition and reduction) in a 5-step elongation cycle, to synthesize a c16 fatty acids
- Reaction intermediates are attached to acyl carrier protein, serving as a molecular foundation for the fatty acid being constructed (molecular scaffold)
Fatty Acids Synthesis: Stage 1 – Transport
Fatty acids synthesis takes place in cytoplasm
- Citrate is synthesized in mitochondria ~ from condensation reaction w/ acetyl-CoA + oxaloacetate
- Citrate must be transported into cytoplasm ~ citrate transporters
- Citrate cleaved by ATP-citrate lyase
- Generates acetyl-CoA for fatty acid synthesis
- Oxaloacetate released
- Entire reaction cost = 1 ATP - During transport of citrate from mitochondria into cytoplasm, the oxaloacetate generated is converted to malate by malate-dehydrogenase
- Malate converted to pyruvate by malic enzyme
- Produces 1 NADH reducing power - Pyruvate enters mitochondria and converted to oxaloacetate by pyruvate carboxylase
Fatty Acids Synthesis: Stage 2 – Activation of Acetyl-CoA
Synthesis starts w/ carboxylation of acetyl-CoA to form malonyl-CoA (3-C)
The synthesis is a commitment, irreversible, and regulatory step
Catalyzed by acetyl-COA carboxylase 1
- A biotin-requiring enzyme
- A regulatory enzyme
Formation of malonyl-CoA occurs in two steps:
- The biotin carboxylase (BC) activity of the enzyme catalyzes formation of a carboxybiotin intermediate at expense of the hydrolysis of 1 ATP
Biotin enzyme + ATP + HCO3 = CO2-biotin
- The activated CO2 group is then transferred to acetyl-CoA to form malonyl-CoA by the carboxyltransferase (CT) activity of the enzyme
CO2-biotin + acetyl-CoA = malonyl-CoA + biotin-enzyme
What is the net reaction for the formation of malonyl-CoA
acetyl-CoA + ATP + HCO3 –> Malonyl-CoA + ADP + Pi + (H+)
Fatty Acids Synthesis: Stage 3 – Repeated Addition/Reduction of 2-C Units
Involves a series of repeated reactions:
- Condensation, reduction, dehydration, and reduction reactions
Fatty acid synthase = the enzyme that catalyzes the synthesis of saturated long fatty acids from acetyl-CoA, malonyl-COA, and NADH
- The synthase is a complex of distinct enzymes, each w/ different functions in fatty acids synthesis ~ a multifunctional enzyme complex
In animals, all the enzymes required for fatty acid synthesis are components of a single polypeptide chain
- Multifunctional enzyme is composed of 2 identical chains w/ 2-active sites
- The multifunctional enzyme also consists of two distinct compartments:
- Condensing compartment: binds the acetyl and malonyl substrates and condenses them
- Modification compartment: carries out reduction and dehydration activities required for elongation during fatty acid synthesis
Fatty Acid Synthesis via FA Synthase
Fatty acid synthesis occurs on acyl carrier protein (ACP) ~ a polypeptide w/ CoA like thiol
Intermediates are linked to sulfhydryl group of the phosphopanthetine group attached to ACP
Acetyl transacylase and malonyl transacylase (MAT) attach substrates to ACP
B-ketoacyl synthase (KS; condensing enzyme) catalyzes condensation of acetyl ACP and malonyl ACP to form acetoacetyl ACP
Next three steps – reduction (KR; ketoacyl reductase), dehydration (DH; dehydratase), and another reduction (ER; enoyl reductase)
- through these reactions a keto group at carbon 3 is converted to a methylene group (-CH2-), forming butyryl ACP
NADPH = source of reducing power for the reactions
Fatty acid synthesis ______ generate fatty acids longer than ___________ and _______ generate double bonds
a) cannot; C16 palmitate; cannot
b) can; C16 palmitate; can
c) can C18 palmitate; cannot
c) cannot; C18 palmitate; cannot
a) cannot; C16 palmitate; cannot
Longer fatty acids are synthesized by ________________
a) epithelial cells attached to the intestine
b) membrane bound enzymes attached to ER
c) membrane bound enzymes attached to lysosomes
d) membrane bound enzymes attached to golgi body
b) membrane bound enzymes attached to ER
With regards to longer fatty acids that are synthesized by membrane bound enzymes attached to the ER, these enzymes can extend past palmitate (C16) by _____________
a) adding 2 carbon units, using acetyl-CoA as a substrate
b) adding 4 carbon units, using malonyl-CoA as a substrate
c) adding 2 carbon units, using propionyl-CoA as a substrate
d) adding 2 carbon units, using malonyl-CoA as a substrate
d) adding 2 carbon units, using malonyl-CoA as a substrate
True or False: With respect to the membrane bound enzymes attached to the ER, they cannot introduce double bonds into saturated fatty acids
False
Enzymes bound to ER can introduce double bonds into saturated fatty acids
True or False: Mammals lack the enzymes that introduce double bonds beyond carbon 9 ~ demonstrates physiological limits to the types of fatty acids we can synthesize in our cells
True
True or False: Linoleate is an essential fatty acid that must be must be obtained from the diet, while linolenate is a non-essential fatty acid
False
Linoleate and linolenate are both essential fatty acids, needed to be obtained from the diet
Which of the following is TRUE with respect to Arachidonate?
a) is a 20-carbon fatty acid with 4 double bonds
b) is also referred to as eicosanoids
c) is an 18-carbon fatty acid with 2 double bonds
d) is derived from linolenate
e) is derived from lineolate
f) is a precursor for a variety of signal molecules
a, b, e, f
Which of the following is TRUE with respect to Acetyl-CoA carboxylase?
a) it is a key regulator of fatty acid metabolism
b) it is regulated by conditions in the cells
c) it is not a key regulator of fatty acid metabolism
d) acetyl-CoA carboxylase 1 and 2 are subject to regulation on several levels
a, b, d
Which of the following is TRUE with respect to carboxylase 1?
a) is is a mitochondrial enzyme
b) it is a cytoplasmic enzyme
c) it is Inhibited when phosphorylated by AMP-activated kinase (AMPK)
d) Phosphorylation is reversed by protein phosphatase 2A
e) it inhibits carnitine acetyltransferase I
b, c, d
