Question

It has been stated many times that fatty acids cannot yield a net gain in carbohydrates. Why can odd-chain fatty acids be thought to break this rule to a small extent?

Short answer

Odd-chain fatty acids yield propionyl-CoA, which converts to succinyl-CoA and can enter gluconeogenesis, enabling some carbohydrate synthesis.

Step-by-step solution

Identifying the Problem

Understand that the premise is about fatty acids typically not yielding a net gain in carbohydrates. The task is to examine how odd-chain fatty acids might deviate from this rule.

Understanding Fatty Acid Metabolism

First, recognize that during β-oxidation, fatty acids are broken down to produce acetyl-CoA, which enters the citric acid cycle. Even-chain fatty acids fully convert to acetyl-CoA.

Odd-Chain Fatty Acids Breakdown

Odd-chain fatty acids undergo β-oxidation, but their final products are one acetyl-CoA and one propionyl-CoA, unlike even-chain fatty acids that only yield acetyl-CoA.

Conversion of Propionyl-CoA to Succinyl-CoA

Understand that propionyl-CoA can be converted to succinyl-CoA, which is an intermediate in the citric acid cycle. This step distinguishes odd-chain fatty acids.

Succinyl-CoA's Role

Since succinyl-CoA is a citric acid cycle intermediate, it can be converted to oxaloacetate, which can then be used in gluconeogenesis to form glucose, contributing to carbohydrate synthesis.

Gluconeogenesis

Explain gluconeogenesis: the process in which oxaloacetate is ultimately converted into glucose, allowing for a net gain of carbohydrates from odd-chain fatty acids to a small extent.

Key concepts

β-oxidation

Fatty acid metabolism primarily begins with β-oxidation. This is the process by which fatty acids are broken down in the mitochondria to generate acetyl-CoA, the key molecule for several metabolic pathways. Each cycle of β-oxidation shortens the fatty acid chain by two carbon atoms, resulting in the production of acetyl-CoA. Understanding this is crucial because it lays the foundation for how different types of fatty acids are metabolized. Regularly, even-chain fatty acids only produce acetyl-CoA through this process.

acetyl-CoA

Acetyl-CoA is an essential molecule in metabolism. Formed through β-oxidation, it enters the citric acid cycle (or Krebs cycle) to release energy. This molecule is involved in several metabolic processes, but one critical point to note is that it cannot be converted back to pyruvate or generate glucose directly through gluconeogenesis. This is why fatty acids are usually not considered glucogenic. However, they provide energy through the citric acid cycle while continuing to highlight the unique case of odd-chain fatty acids.

propionyl-CoA

Propionyl-CoA is a product unique to the metabolism of odd-chain fatty acids. Unlike even-chain fatty acids that fully break down into multiple acetyl-CoA molecules, odd-chain fatty acids eventually yield propionyl-CoA in the final step of β-oxidation along with one acetyl-CoA. Propionyl-CoA is a three-carbon molecule, which places it in a distinct metabolic pathway that ultimately connects to the citric acid cycle.

succinyl-CoA

Propionyl-CoA undergoes a series of reactions to be converted into succinyl-CoA. This is a crucial step, as succinyl-CoA is an intermediate in the citric acid cycle. The conversion involves several enzymes and cofactors, notably biotin and vitamin B12. The transition from propionyl-CoA to succinyl-CoA is one of the key factors that allows odd-chain fatty acids to break the general rule about fatty acids and carbohydrate production, leading us to our next important process.

citric acid cycle

The citric acid cycle, also known as the Krebs cycle or TCA cycle, is central to cellular respiration. Acetyl-CoA and succinyl-CoA both enter this cycle, contributing to energy production through the series of reactions that release stored energy from carbohydrates, fats, and proteins. When succinyl-CoA enters the citric acid cycle, it transforms further and can produce oxaloacetate. This is the entry molecule for gluconeogenesis, leading to the potential production of glucose from odd-chain fatty acids.

gluconeogenesis

Gluconeogenesis is the process through which glucose is synthesized from non-carbohydrate sources. In the case of odd-chain fatty acids, the intermediate succinyl-CoA from the citric acid cycle can convert to oxaloacetate. Then, oxaloacetate serves as a precursor in gluconeogenesis to generate glucose. This unique pathway allows for a net gain in carbohydrates, albeit small, breaking the conventional rule that fatty acids do not contribute to carbohydrate synthesis. The process highlights the exceptional metabolic flexibility present in odd-chain fatty acid metabolism.