Question

During the synthesis of palmitate in liver cells, A. the addition of malonyl CoA to fatty acid synthase elongates the growing chain by three carbon atoms. B. \(a \beta\) -keto residue on the \(4^{\prime}\) -phosphopantetheine moiety is reduced to a saturated residue by NADPH. C. palmitoyl CoA is released from the synthase. D. transfer of the growing chain from ACP to another - SH occurs prior to addition of the next malonyl CoA. E. the first compound to add to fatty acid synthase is malonyl CoA.

Short answer

A) The addition of malonyl CoA to fatty acid synthase elongates the growing chain by three carbon atoms. B) An \(a \beta\) -keto residue on the \(4^{\prime}\) -phosphopantetheine moiety is reduced to a saturated residue by NADPH. C) Palmitoyl CoA is released from the synthase when the desired length of the fatty acid chain is achieved. D) Transfer of the growing chain from ACP to another - SH occurs prior to the addition of the next malonyl CoA. E) The first compound to add to fatty acid synthase is malonyl CoA. Answer: B, C, and D are true statements regarding the synthesis of palmitate in liver cells.

Step-by-step solution

Understanding the process of fatty acid synthesis involving malonyl CoA

Fatty acid synthesis is a process where the chain of growing fatty acids is elongated by the addition of new carbon atoms. Malonyl CoA plays an important role in this elongation as it donates the carbon atoms to the growing chain.

Elongation by three carbon atoms

The addition of malonyl CoA to fatty acid synthase elongates the growing chain by three carbon atoms. This statement is true. The malonyl CoA molecule donates two carbon atoms to the fatty acid synthase enzyme, but one carbon atom is released as carbon dioxide during this elongation process. Thus, it means that the net addition of carbon atoms is actually two, not three. Answer A is incorrect.

Reduction of \(a \beta\) -keto residue by NADPH

\(a \beta\) -keto residue on the \(4^{\prime}\) -phosphopantetheine moiety is reduced to a saturated residue by NADPH. This statement is true. During fatty acid synthesis, NADPH reduces the \(a \beta\) -keto residue forming a saturated residue and oxidizing NADPH to NADP+. Answer B is correct.

Release of palmitoyl CoA from the synthase

Palmitoyl CoA is released from the synthase when the desired length of the fatty acid chain is achieved. This statement is true. Once the fatty acid chain reaches 16 carbon atoms, palmitoyl CoA is released from the fatty acid synthase. Answer C is correct.

Transfer of the growing chain prior to the addition of next malonyl CoA

Transfer of the growing chain from ACP to another - SH occurs prior to the addition of the next malonyl CoA. This statement is true. The growing chain is transferred from the -SH of the ACP to the -SH of the cysteine residue on the fatty acid synthase enzyme. The transfer allows for the addition of another malonyl CoA molecule. Answer D is correct.

Malonyl CoA as the first compound to add to fatty acid synthase

The first compound to add to fatty acid synthase is not malonyl CoA. Instead, the first compound that adds to fatty acid synthase is acetyl CoA, which provides the first two carbon atoms to initiate the chain. After the initial addition, subsequent carbon molecule additions use malonyl CoA. Answer E is incorrect.

Key concepts

Malonyl CoA

Malonyl CoA serves as a critical two-carbon donor in fatty acid synthesis. When we dive into the cellular mechanics of synthesizing fatty acids, we encounter malonyl CoA as the building block that contributes to chain elongation.

During the synthesis process, malonyl CoA adds its two carbons to the nascent fatty acid chain, but here's a twist: one carbon is released as CO2, effectively resulting in the net addition of just one carbon to the chain. This reaction is catalyzed by the fatty acid synthase complex, an intricate enzyme system, which is capable of performing multiple steps in a cyclic fashion until a long fatty acid chain is synthesized.

A common misconception, highlighted in the exercise, is the belief that malonyl CoA adds three carbons to the growing chain rather than two, which is worth noting to avoid errors in understanding fatty acid biosynthesis.

NADPH Reduction in Fatty Acid Synthesis

Rain or shine, NADPH is the favorite reducing agent for cellular biosynthetic processes, with fatty acid synthesis being no exception. After acetyl CoA initiates the fatty acid chain, each addition of a two-carbon unit from malonyl CoA results in an intermediate called \( \beta \) -ketoacyl-ACP, which needs to be reduced to continue growing the chain.

This is where NADPH steps in, heroically donating electrons to convert the \( \beta \) -keto group to a hydroxyl group, and subsequently, to a fully saturated carbon chain via a series of reduction and dehydration reactions. Learning this is crucial because it delineates how the energy-rich NADPH is oxidized to NADP+, illustrating its key role in the biogenesis of fatty acids.

Palmitoyl CoA Release

In the grand finale of fatty acid synthesis, when the carbon chain gracefully reaches a sweet 16 - that is, 16 carbon atoms long - it's known as palmitate. This molecule is still tethered to the fatty acid synthase complex through a thioester bond to Coenzyme A (CoA).

The release of palmitate as palmitoyl CoA marks the end of the fatty acid synthesis cycle. This liberating step is significant because it releases the completed fatty acid for further modifications or for being shunted into cellular processes such as the formation of phospholipids or being stored as energy in the form of triglycerides. The understanding of this release mechanism is vital because it controls the termination of the chain-elongating process and dictates the primary product of fatty acid synthesis.

Fatty Acid Synthase Mechanism

Fatty acid synthase is akin to a mini-factory within our cells, primarily responsible for churning out saturated fatty acids. This multi-enzyme complex performs a series of reactions to synthesize fatty acids, initiated by acetyl CoA and further elongated by malonyl CoA.

The mechanism involves repetitive cycles of chain elongation, each comprising of loading, condensation, reduction, dehydration, and another reduction. In each cycle, the fatty acid synthase complex transfers the growing fatty acid chain on its acyl carrier protein (ACP) to the active site cysteine via a transacylation reaction, making room for the next malonyl CoA molecule to join the cascade. This intricate dance of enzymatic steps is orchestrated with precision, and each step is crucial for the efficient synthesis of fatty acids. Clear understanding of the fatty acid synthase mechanism requires focusing on the details of each reaction step and the enzyme's structural choreography.