A) Fats are hydrolyzed in the presence of carbohydrates
B) Fatty acids and glucose are simultaneously oxidized
C) Acetyl co A is the common product of fatty acid and glucose oxidation
D) Acetyl co A is oxidized completely in the presence of oxaloacetate in TCA cycle
The correct answer is D) – Acetyl co A is oxidized completely in the presence of oxaloacetate in TCA cycle.
Fats burn in the flame of carbohydrates means fats can only be oxidized in the presence of carbohydrates.
Oxidation of fats
Fats includes triglycerides, cholesterol (free or esterified), free fatty acids and their derivatives such as phospholipids and other complex lipids. The end product of metabolism of almost all these fats is Acetyl co A. Hence, Acetyl co A can be considered a fat derivative. There are many other sources (figure-1), but fatty acid oxidation is the major source of Acetyl co A.
Figure-1- Sources of Acetyl co A: The major contribution of Acetyl Co A is from fatty acid oxidation, the pathways of fatty acid oxidation (minor and major), end up forming Acetyl Co A. Pyruvate, ketogenic amino acids and acetylcholine also contribute to Acetyl co A pool. The ketone bodies are synthesized from and are metabolized to Acetyl Co A.
Fate of Acetyl Co A
Acetyl Co A can be metabolized in many ways (figure-2); It is a precursor of fatty acids, cholesterol, steroids, ketone bodies, and Acetylcholine. It is also required for the detoxification of xenobiotics, but the major fate involves complete oxidation in the TCA cycle to provide energy.
Figure-2- Central role of Acetyl co A: Acetyl Co A can be utilized in multiple ways depending upon the cell type and under different cellular conditions. Under low energy states, Acetyl co A is completely oxidized in the TCA cycle to provide energy.
Oxidation of Acetyl Co A in TCA cycle
The citric acid cycle is the central metabolic hub of the cell. It is the final common pathway for the oxidation of fuel molecule such as amino acids, fatty acids, and carbohydrates. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid. The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) includes a series of oxidation-reduction reactions in mitochondria that result in the oxidation of an acetyl group to two molecules of carbon dioxide and reduce the coenzymes that are reoxidized through the electron transport chain, linked to the formation of ATP.
A four- carbon compound (oxaloacetate) condenses with a two-carbon acetyl unit to yield a six-carbon tricarboxylic acid (citrate). An isomer of citrate is then oxidatively decarboxylated. The resulting five-carbon compound (α-ketoglutarate) also is oxidatively decarboxylated to yield a four carbon compound (succinate) (Figure-3).
Figure-3- An overview of TCA cycle
Oxaloacetate is then regenerated from succinate. Two carbon atoms enter the cycle as an acetyl unit and two carbon atoms leave the cycle in the form of two molecules of carbon dioxide. This is considered as the complete oxidation of Acetyl co A having two carbon atoms in its structure.1 acetate unit generates approximately 12 molecules of ATP.
The four-carbon molecule, oxaloacetate that initiates the first step in the citric acid cycle is regenerated at the end of one passage through the cycle. The oxaloacetate acts catalytically: it participates in the oxidation of the acetyl group but is itself regenerated. Thus, one molecule of oxaloacetate is capable of participating in the oxidation of many acetyl molecules.
Sources and Fate of Oxaloacetate
Oxaloacetate can be synthesized from or metabolized to Aspartate (figure-4) in reversible transamination reaction. Aspartate can be used for the synthesis of purines and pyrimidines; it is also used in urea cycle. The major source of Oxaloacetate is pyruvate in a reaction catalyzed by Pyruvate carboxylase.
Pyruvate is mainly used up for Anaplerotic reactions to compensate for oxaloacetate concentration. Thus without carbohydrates (Pyruvate), there would be no Anaplerotic reactions to replenish the TCA-cycle components. With a diet of fats only, the acetyl CoA from fatty acid degradation would not get oxidized and build up due to non- functioning of TCA cycle. Thus fats can burn only in the flame of carbohydrates -Figure-5
Figure-4- Role of Oxaloacetate in TCA cycle. Oxaloacetate acts as a catalyst of TCA cycle; it starts the cycle and is regenerated at the end of the cycle.
It can now be well concluded that the complete oxidation of Acetyl Co A, a derivative of fats cannot take place without the availability the derivative of carbohydrates, that is oxaloacetate,. Hence the statement “fats burn in the flame of carbohydrates”, is absolutely correct.
Figure-5- Significance of oxaloacetate in TCA cycle operation.
As regards other options
A) Fats are hydrolyzed in the presence of carbohydrates -is incorrect. Fats are not hydrolyzed in the presence of carbohydrates.
B) Fatty acids and glucose are simultaneously oxidized- It is also not true. The location, enzymes, the nutritional states, the regulatory hormones are different for these oxidative processes. Fatty acid oxidation mainly takes place during period of starvation, in the presence of glucagon or catecholamines whereas glycolysis takes place in the well fed state in the presence of insulin as the regulatory hormone.
C) Acetyl co A is the common product of fatty acid and glucose oxidation- The end product undoubtedly is Acetyl Co A but without oxaloacetate, Acetyl co A cannot be oxidized.
Therefore, D) Acetyl co A is oxidized completely in the presence of oxaloacetate in TCA cycle, is the correct option.
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