Lipids 5- Metabolism and Fatty Acid Synthesis Flashcards

Vocabulary flashcards covering lipid metabolism, fatty acid synthesis, and related concepts from biochemistry lecture notes.

Fatty Acid Synthesis Location

Occurs in the cytoplasm of prokaryotes and adipocytes, and liver cells of eukaryotes.

Citrate-Malate Shuttle

Transports Acetyl CoA from the mitochondria to the cytoplasm for fatty acid synthesis because the inner mitochondrial membrane is impermeable to Acetyl CoA.

Acetyl CoA Carboxylase I (ACC)

The enzyme that catalyzes the committed step in fatty acid synthesis, converting acetyl CoA to malonyl CoA.

Requires ATP hydrolysis to proceed

Malonyl CoA

Formed when Acetyl CoA is condensed with bicarbonate, catalyzed by acetyl CoA carboxylase I (ACC).

• malonyl CoA is the actual carbon donor for all but two of the carbon atoms of palmitic acid

ACC Regulation: Covalent Modification

Insulin stimulates phosphatase, leading to dephosphorylation and activation of Acetyl CoA carboxylase. Glucagon/Epinephrine stimulates protein kinase, leading to phosphorylation and inactivation.

ACC Regulation: Allosteric

Citrate activates Acetyl CoA carboxylase; Palmitoyl CoA inhibits.

Acyl Carrier Protein (ACP)

Serves as a scaffold in fatty acid synthesis, with intermediates attached to the sulfhydryl end of an ACP group

Malonyl-CoA-ACP Transacylase (MAT)

The enzyme that catalyzes the transfer of the malonate group to Acyl Carrier Protein (ACP).

• generates malonyl ACP upon which the fatty acid is built

Fatty Acid Synthesis Steps

1. Condensation, 2. Reduction of the carbonyl group, 3. Dehydration, 4. Reduction of the double bond.

β-ketoacyl synthase

The enzyme that catalyzes the condensation of malonyl ACP with acetyl ACP, extending the acyl group by two carbons.

3-ketoacyl-ACP reductase

The enzyme that catalyzes the reduction of the carbonyl group using NADPH as the electron donor.

β-hydroxyacyl ACP dehydratase

The enzyme that catalyzes the dehydration of D-3-hydroxybutyryl ACP, generating a trans double bond.

Enoyl ACP reductase

The enzyme that catalyzes the reduction of the C=C bond, using NADPH as the electron donor.

Palmitoyl-protein thioesterase (PPT)

The enzyme that cleaves the thioester linkage connecting the 16C acyl group with ACP, releasing palmitate.

Elongases

Anabolic enzymes attached to the endoplasmic reticulum membrane that are involved in generating products with more than 16 carbons.

Desaturases

Enzymes that introduce cis double bonds at particular locations in fatty acids to generate an unsaturated fatty acid

Essential Fatty Acids

Linolenic acid (ω3) and linoleic acid (ω6) which cannot be synthesized by humans and must come from the diet. Humans cannot introduce double bonds beyond carbon-9.

Odd chain saturated fatty acid synthesis location

Cytoplasm via same anabolic pathway

How many acetyl CoA must be transported?

Depends on hydrocarbon length; actyl CoA a 2-carbon carrier

Synthesis of palmitate (16:0)

Would need 8 acetyl CoA

Acetyl CoA

The end product of fatty acid degradation and is the precursor for all fatty acids

Biochemical Challenge

Link the 2-carbon units together and reduce the carbon atoms to produce palmitate, a C16 fatty acid that serves as a precursor for a variety of fatty acids

Fatty acid synthase

Enzyme system that catalyzes the synthesis of saturated long-chain fatty acids from acetyl CoA, malonyl CoA and NADPH is called

Steps in fatty acid synthesis repeat until

Palmitate (16:0) is made

Generation of a saturated, even chain fatty acid

Pathway extends the hydrocarbon chain two carbons at a time

Step 1: condensation

First reaction is the condensation of malonyl ACP with acetyl ACP

• enzyme= B-ketoacyl synthase

• Reaction extends acyl group by 2 carbons

• products: acetoacetyl ACP and CO2

Step 2: Reduction of carbonyl group

The second reaction is the reduction of the carbonyl group by a reductase

• enzyme= 3-ketoacyl-ACP reductase

• NADPH is the electron donor

• reaction converts keto group to hydroxyl group at carbon-3

• product: D-3-hydroxybutyryl ACP

Step 3: Dehydration

The third reaction is the dehydration of D-3-hydroxybutyryl ACP by a dehydrogenase

• enzyme= B-hydroxyacyl ACP dehydratase

• reaction generates trans double bond between carbon 2 and 3

• Product: crotonyl ACP and H2O

Step 4: Reduction of the double bond

The fourth reaction is reduction of the Carbon carbon double bond by a reductase

• enzyme= Enoyl ACP reductase

• NADPH is the electron donor

• reaction generates single bond between carbon 2 and 3

• product: butyryl ACP

Final product: Butyryl ACP

Condenses with a new molecule of malonyl ACP (step 1)

• forms C6-B-ketoacyl ACP; acyl group now contains 6 carbons

• reduction, dehydration, and reduction (steps 2-4) then follow

• repeats until C16-acyl ACP is formed

Front-end desaturases

Humans have these specifically at delta 4, delta 6, and delta 9 positions. But have no methyl-end desaturases (like omega-3 and omega-6)

Propionate (contains 3-carbons)

Transferred to an ACP and condensed with malonyl ACP which generates a 3-oxovaleryl ACP (has 5 carbons)

Odd chain fatty acid synthesis rounds

each round will add 2 carbons to acyl group (7, 9, 11)

PUFAs

polyunsaturated fatty acids

Acyl chain extension and front-end desaturates process

Humans have enzymes to convert PUFAs within a family

Comparison of beta oxidation and fatty acid synthesis

	FA metabolism	FA synthesis
Location for repeating steps	Mitochondria	Cytoplasm
Carbon number altered via	Thiolysis (step 4)	Condensation (step 1)
Rate-limiting step	Yes with CAT1	No / None
Committed step	No / None	Yes with ACC
Coenzyme(s) involved	NAD+ and FAD	NADPH
Acyl group attached to	CoA	ACP