Lecture 23b

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Questions and Answers

What is the location of fatty acid biosynthesis in animal cells?

Cytosol (correct)

Mitochondria

Chloroplast

Nucleus

What is the product of catabolism of fatty acids?

Acetyl-CoA and NADH (correct)

Malonyl-CoA and NADH

Malonyl-CoA and FADH2

Acetyl-CoA and NADPH

What is the role of NADPH in fatty acid synthesis?

Activates the fatty acid synthase complex

Donates an acetate unit to the growing fatty acid chain

Inhibits the acetyl-CoA carboxylase reaction

Provides reducing power for the reaction (correct)

In which organelle does fatty acid biosynthesis take place in plant cells?

Chloroplast Signup and view all the answers

What is the function of the acetyl-CoA carboxylase reaction in fatty acid synthesis?

Converts acetyl-CoA to malonyl-CoA Signup and view all the answers

How are fatty acids built during synthesis?

One acetate unit at a time Signup and view all the answers

What is the net result of each cycle of condensation and reduction in palmitate synthesis?

Addition of 2 carbon atoms to the fatty acyl chain Signup and view all the answers

How many ATP molecules are required to synthesize 7 malonyl-CoA molecules?

7 ATP Signup and view all the answers

What is the role of NADPH in palmitate synthesis?

To reduce the b-keto group and trans-double bond Signup and view all the answers

What is the functional role of the —SH group in phosphopantetheine during fatty acid synthesis?

Site of entry of malonyl groups Signup and view all the answers

What is the byproduct of the reaction that forms malonyl-CoA from acetyl-CoA?

CO2 + ADP + Pi Signup and view all the answers

What is the primary function of the enzyme thioesterase in fatty acid synthesis?

Releases the palmitate product from ACP Signup and view all the answers

What is the final product of the seven cycles of condensation and reduction in palmitate synthesis?

A fatty acid with 16 carbon atoms Signup and view all the answers

What is the additional energy cost in eukaryotes for palmitate synthesis?

2 ATP Signup and view all the answers

What is the byproduct of the condensation reaction between an activated acyl group and malonyl-CoA?

CO2 only Signup and view all the answers

What is the role of the enzyme β-ketoacyl-ACP reductase in fatty acid synthesis?

Reduction of the carbonyl to hydroxyl Signup and view all the answers

What is the function of the acyl carrier protein (ACP) in fatty acid synthesis?

Carries the growing fatty acyl chain Signup and view all the answers

What is the characteristic of the mammalian fatty acid synthase (FAS I)?

A homodimer of a single 240 kD polypeptide with all catalytic activities Signup and view all the answers

What is the effect of an increase in acetyl-CoA concentration on citrate production?

Citrate production is activated Signup and view all the answers

Which of the following hormones phosphorylates and inactivates ACC when energy is needed?

Two answers are correct Signup and view all the answers

What is the feedback inhibitor of ACC?

Palmitoyl-CoA Signup and view all the answers

What is the result of insulin signaling on ACC activity?

ACC is dephosphorylated and activated Signup and view all the answers

What is the purpose of citrate in fatty acid synthesis regulation?

To signal energy excess Signup and view all the answers

What is the primary source of electrons for the desaturation of fatty acids in vertebrates?

NADPH Signup and view all the answers

Study Notes

Lipid Metabolism: Fatty Acid Biosynthesis

Origin of cytoplasmic acetyl-CoA is crucial for fatty acid synthesis.
Acetyl-CoA carboxylase (ACC) catalyzes the conversion of acetyl-CoA to malonyl-CoA, a key regulatory step.
Fatty acid synthesis occurs in the cytosol of animals and chloroplasts of plants; it requires NADPH as a reducing agent.

Catabolism vs. Anabolism

Catabolism: Oxidation of fatty acids, producing acetyl-CoA and NADH; occurs in mitochondria.
Anabolism: Synthesis of fatty acids using acetyl-CoA and malonyl-CoA; accompanied by NADPH reduction in the cytosol.

Overview of Fatty Acid Synthesis

Fatty acids are constructed by adding two-carbon units from activated malonate.
The initial acetyl group from acetyl-CoA starts the synthesis process, followed by dehydration and reductions.
Final product of the synthesis is palmitate (16:0).

Stoichiometry of Palmitate Synthesis

Formulation involves seven malonyl-CoA derived from carboxylating seven acetyl-CoA.
Synthesis uses 7 acetyl-CoA, 14 NADPH, and ATP contributing to the overall energy balance.
Eukaryotes incur an extra ATP cost to shuttle acetyl-CoA into the cytosol.

Fatty Acid Synthase Type I (FAS I)

FAS I is a multi-catalytic complex responsible for fatty acid synthesis in mammals.
Contains specific sites: condensation (KS), reduction (KR), dehydration (DH), and a thioesterase (TE) for product release.

Repeating Sequence of Reactions

Process involves the condensation of an acyl group with malonyl groups, elongating the fatty acyl chain by two carbon units.
The overall ATP cost is three per two-carbon unit after considering initial costs and reductions.

Regulation of ACC

Acetyl-CoA carboxylase is the rate-limiting enzyme in fatty acid synthesis.
ACC activity is regulated via allosteric mechanisms (inhibited by palmitoyl-CoA and activated by citrate).
Hormonal regulation occurs; insulin activates while glucagon and epinephrine inhibit ACC through phosphorylation.

Regulation in Vertebrates

Both allosteric and hormonal signalings influence malonyl-CoA flow, impacting fatty acid synthesis.
Insulin triggers accumulation of active ACC while glucagon promotes its inactivation.

Desaturation of Fatty Acids

Humans can only desaturate fatty acids up to position D9; cannot further desaturate beyond this.
Plants can produce essential fatty acids such as linoleate and α-linolenate, which are crucial for human health.
Polyunsaturated fatty acids (PUFAs) maintain membrane fluidity and serve as precursors to eicosanoids.

Mechanism of Fatty Acyl Desaturase

Vertebrate fatty acyl desaturase is a mixed-function oxidase utilizing O2 to convert saturated fatty acids to unsaturated forms.
Electron transfer involves NADPH and cytochrome b5, occurring on the smooth endoplasmic reticulum's lumenal face.

These notes capture various fundamental aspects of lipid metabolism and fatty acid biosynthesis as relevant to biochemistry studies.

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