Fundamentals of Molecular Biology. Part 1: Molecular Biology of the Cell - A. N. Ogurtsov 2011

Glucose and Fatty Acid Oxidation
Fatty Acid Oxidation

Fatty acids are stored in the body as triacylglycerols, predominantly as droplet inclusions within adipose tissue Cells, or adipocytes. In response to Hormones such as adrenaline, triacylglycerols are hydrolyzed in the Cytosol into Fatty Acids and glycerol (Figure 159).

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Figure 159 – Scheme of triacylglycerol Hydrolysis

Fatty acids then enter the bloodstream and are utilized (oxidized) by most cells in the body, serving as a major energy source. Specifically, the Oxidation of Fatty acids in The Human Body quantitatively yields more ATP than glucose METABOLISM. The oxidation of 1 gram of triacylglycerols to CO₂ yields six times more ATP than the oxidation of 1 gram of Glycogen.

Triacylglycerols are more efficient for energy storage compared to CARBOHYDRATES because the carbons in their —(Н—С—Н)_n— chains are much more reduced than the carbons in the -(Н-С-ОН)- groups of carbohydrates; consequently, their oxidation releases more energy.

In the cytosol, fatty acids are esterified with coenzyme A in a reaction coupled with ATP hydrolysis, forming activated fatty acids in the form of acyl-CoA:

Subsequent hydrolysis of pyrophosphate PP_i drives this reaction to completion. Next, the enzyme carnitine acyltransferase attaches the activated fatty acid to carnitine (Figure 160).

Figure 160 – Scheme of acylcarnitine formation

7.9.1. Fatty acid oxidation in Cell/35.html">Mitochondria. In the form of acylcarnitine, the fatty acid is transported across The inner mitochondrial membrane by the acylcarnitine transporter protein (Figure 154, left). Within the matrix, the fatty acid is detached from carnitine and reattached to coenzyme A, regenerating acyl-CoA.

Through a cyclic sequence of four reactions, each fatty acyl-CoA molecule in the mitochondrial matrix is oxidized, becoming shorter by two CH₂ groups in each cycle and generating acetyl-CoA, along with NADH and FADH₂ (Figure 161(a)).

For instance, the mitochondrial oxidation of each 18-carbon stearic acid molecule, CH₃(CH₂)₁₆COOH, results in The formation of 9 molecules of acetyl-CoA, 9 molecules of NADH, and 9 molecules of FADH₂.

The acetyl-CoA molecules synthesized during this oxidation are subsequently utilized in the citrate cycle, where they are oxidized to CO₂.

Meanwhile, the electrons released from the reduced Coenzymes (which are generated during the oxidation of fatty acyl-CoA to acetyl-CoA, and subsequently in the citrate cycle during the oxidation of acetyl-CoA to CO₂, and are delivered to the Respiratory Chain as NADH and FADH₂) travel along the Respiratory Chain and ultimately reduce molecular oxygen to O₂. This electron transfer is energetically coupled with the generation of a proton-motive force, which is then utilized for ATP synthesis.

Figure 161 – Scheme of fatty acid oxidation processes: a – in the mitochondrial matrix (left part of the figure); b – in Peroxisomes (right part of the figure)

7.9.2. Fatty Acid Oxidation in Peroxisomes. Fatty acid oxidation also occurs in peroxisomes, much like in mitochondria. Peroxisomes are present in all mammalian cells except erythrocytes, as well as in plants and Yeasts—they are likely found in all Eukaryotic cells. Peroxisomes are responsible for the oxidation of a substantial portion of fatty acids. Notably, fatty acids with a hydrocarbon tail longer than 20 CH₂ groups are oxidized exclusively in peroxisomes. In mammalian cells, medium-chain fatty acids (10–20 CH₂ groups) are degraded in both mitochondria and peroxisomes.

Unlike mitochondria, where fatty acid oxidation is coupled with ATP synthesis, oxidation processes in peroxisomes are not linked to ATP production, and the released energy is simply dissipated as heat.

In peroxisomes, The sequence of reactions by which fatty acids are degraded to acetyl-CoA is similar to that in mitochondria (Figure 161(b)). However, peroxisomes lack respiratory chains; instead, electrons from FADH₂ molecules generated during fatty acid oxidation are transferred to O₂ by two Enzymes. First, an oxidase regenerates FAD molecules and synthesizes hydrogen peroxide H₂O₂; then, since hydrogen peroxide is a toxic metabolite, it is immediately decomposed by the enzyme catalase.

NADH molecules produced during fatty acid oxidation are exported from the peroxisome and subsequently oxidized to NAD^⊕ in the cytosol. Peroxisomes lack the Enzymes of the citrate cycle; therefore, the acetyl-CoA molecules resulting from fatty acid oxidation are transported out of the peroxisome into the cytosol, where they are subsequently used in the synthesis of Cholesterol and other metabolites.

Review Questions

1. What is The Role of ATP in providing cells with the energy required to drive endergonic reactions?

2. Through which processes is the energy required for the synthesis of ATP from ADP and P_i obtained?

3. What is chemiosmosis?

4. What is the proton-motive force? Through which processes is it generated?

5. Which Proteins utilize the proton-motive force for ATP synthesis?

6. How is ATP synthase oriented within the membranes of mitochondria, Chloroplasts, and Bacteria?

7. What does the Endosymbiotic Hypothesis propose?

8. In what forms is chemical potential energy stored during bioenergetic processes?

9. How do ATP Pumps, Ion Channels, and carriers differ from one another?

10. Which type of transmembrane transport is referred to as active?

11. How do uniport, symport, and antiport differ?

12. How does secondary Active Transport differ from primary active transport?

13. Compare the rates of molecular transport across membranes mediated by ATP pumps, ion channels, and secondary active transporters.

14. How many ATP molecules are synthesized As a result of the complete aerobic oxidation of a single glucose molecule?

15. What is Glycolysis? Write out the overall equation for glycolysis.

16. What are the Similarities and differences between the oxidation processes of nicotinamide adenine dinucleotide and flavin adenine dinucleotide?

17. What is substrate-level phosphorylation? At which stages of glycolysis does substrate-level phosphorylation take place?

18. How does glucose metabolism differ between obligate aerobic and facultative anaerobic cells?

19. Which type of glucose metabolism is referred to as Fermentation? How does fermentation differ from glycolysis?

20. How does anaerobic Glucose metabolism in Yeast cells differ from that in mammalian Muscle cells?

21. Which process is known as cellular Respiration?

22. Which energy-yielding processes are associated with the inner mitochondrial membrane?

23. Name the three main groups of reactions involved in the Oxidation of Pyruvate and fatty acids within mitochondria.

24. What is the role of The Citric Acid Cycle in cellular respiration?

25. What is the role of acetyl-CoA in The Tricarboxylic Acid Cycle?

26. At which stage of the Krebs cycle does substrate-level phosphorylation occur?

27. How many molecules of the coenzymes NADH and FADH₂ are reduced per molecule of glucose during glycolysis and The Citric Acid cycle combined?

28. Which mitochondrial membrane complex mediates The transfer of electrons from cytosolic NADH to mitochondrial matrix NADH?

29. What are the Components of the malate-aspartate shuttle?

30. How do fatty acids cross from the cytosol into the mitochondrial matrix during mitochondrial fatty acid oxidation? What is the role of acyl-CoA in this process?

31. How does fatty acid oxidation in peroxisomes differ from the same process in mitochondria?

32. What is the role of the enzyme catalase in peroxisomal fatty acid oxidation?