12 Questions
What is the first step in the synthesis of odd chain fatty acids?
Decarboxylation of acetoacetyl ACP
What is the reducing agent in the reduction of acetoacetyl ACP in the synthesis of odd chain fatty acids?
NADPH
How is the link between the fatty acid and ACP broken to free the fatty acid for further processing?
Hydrolytic cleavage
Where does the major source of NADPH for synthetic reactions come from in the context of fatty acid synthesis?
Pentose Phosphate Pathway (PPP)
In which step of fatty acid synthesis are 2-C units added to the carboxyl end of both saturated and unsaturated fatty acids?
Synthesis by fatty acid synthase
Which enzyme is responsible for adding double bonds to fatty acids in mammals due to their inability to introduce double bonds after carbon 9?
Oxidase
Which enzyme is responsible for converting oxaloacetate to malate in the citrate cycle?
Malic enzyme
What is the function of pyruvate carboxylase in the citrate cycle?
Formation of citrate from acetyl CoA and oxaloacetate
Which enzyme catalyzes the conversion of acetyl CoA to malonyl CoA?
Acetyl CoA carboxylase
What is the function of fatty acid synthase in fatty acid synthesis?
Synthesizing palmitate in a five-step elongation cycle
What component of fatty acid synthase contains a phosphopantetheine prosthetic group linked to it?
Acyl carrier protein (ACP)
Which enzymes are responsible for linking acetyl CoA and malonyl CoA with the acyl carrier protein (ACP) in fatty acid synthesis?
-SH group and -OH group
Study Notes
Fatty Acid Synthesis
- Odd chain fatty acids are synthesized starting with propionyl CoA, involving 5 steps: decarboxylation, reduction, dehydration, reduction, and final product formation.
- Acetoacetyl ACP (4C) is formed in step 1, releasing CO2 and ACP from acetyl ACP.
- In step 2, acetoacetyl ACP is reduced to 3-hydroxybutyryl ACP using NADPH.
- Step 3 involves dehydration, forming crotonyl ACP with a double bond.
- Crotonyl ACP is reduced to butyryl ACP in step 4, consuming NADPH.
Synthesis of Palmitate
- The final product of fatty acid synthesis is palmitate (16C) linked to ACP by a thioester bond, requiring 6 more rounds of synthesis.
- An enzyme thioesterase is used to hydrolytically cleave the link between the carboxyl group of the fatty acid and the -SH group of ACP.
Energy Requirements
- 8 acetyl CoA, 7 ATP, and 14 NADPH are required for palmitate synthesis, producing 14 NADP+, 8 CoA, 6 H2O, 7 ADP, and 7 Pi.
- NADPH is generated from the pentose phosphate pathway (PPP) and from the entry of acetyl CoA into the cytosol.
Unsaturated Fatty Acids
- Longer fatty acids are synthesized by adding 2-C units to the carboxyl end using malonyl CoA as a substrate, carried by fatty acid synthase.
- Double bonds are introduced by an oxidase using O2 and NADH.
- Dietary essentials like linoleate (18:2) and linolenate (18:3) are omega fatty acids, precursors to other unsaturated fatty acids used in hormone synthesis.
Regulation of Acetyl CoA Carboxylase
- Acetyl CoA carboxylase is regulated by covalent modification and allostery.
- In low-energy states, the enzyme is inhibited due to limited carbohydrates.
- AMP-activated protein kinase phosphorylates and inhibits acetyl CoA carboxylase when AMP levels are high.
Transport of Acetyl CoA
- Acetyl CoA is transported from mitochondria to cytosol by reacting with oxaloacetate to form citrate.
- Citrate is cleaved into acetyl CoA and oxaloacetate in the cytosol.
- Oxaloacetate is reduced to malate using NADH, then to pyruvate by malic enzyme, producing NADPH.
Test your knowledge on the citric acid cycle pathway, which involves the conversion of acetyl CoA to citrate in the mitochondria, followed by a series of enzymatic reactions in the cytosol and mitochondria resulting in the production of NADH and NADPH.
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