Information about Fatty Acid Metabolism

Fatty acids are an important source of energy for many organisms. Excess glucose can be stored efficiently as fat. Triglycerides yield more than twice as much energy for the same mass as do carbohydrates or proteins. All cell membranes are built up of phospholipids, each of which contains two fatty acids. Fatty acids are also used for protein modification. The metabolism of fatty acids, therefore, consists of catabolic processes which generate energy and primary metabolites from fatty acids, and anabolic processes which create biologically important molecules from fatty acids and other dietary carbon sources.

Overview

• Lipolysis is carried out by lipases.
• Once freed from glycerol, free fatty acids can enter blood and muscle fiber by diffusion.
• Beta oxidation splits long carbon chains of the fatty acid into Acetyl CoA, which can eventually enter Krebs Cycle.

Briefly, β-oxidation or lipolysis of free fatty acids is as follows:

1. Dehydrogenation by Fatty Acyl-CoA Dehydrogenase, yielding 1 FADH₂
2. Hydration by Enoyl-CoA Hydratase
3. Dehydrogenation by 3-Hydroxyacyl-CoA dehydrogenase, yielding 1 NADH
4. Cleavage by Thiolase, yielding 1 Acetyl-CoA and a fatty acid that has now been shortened by 2 carbons

This cycle repeats until the FFA has been completely reduced to Acetyl-CoA or, in the case of Fatty acids with odd numbers of carbon atoms, Acetyl-CoA and 1 mol of Propionate per mol of fatty acid.

Fatty acids as an energy source

Fatty acids, stored as triglycerides in an organism, are an important source of energy because they are both reduced and anhydrous. The energy yield from a gram of fatty acids is approximately 9 kcal (39 kJ), compared to 4 kcal/g (17 kJ/g) for proteins and carbohydrates. Since fatty acids are non-polar molecules, they can be stored in a relatively anhydrous (water free) environment. Carbohydrates, on the other hand, are more highly hydrated. For example, 1 g of glycogen can bind approximately 2 g of water, which translates to 1.33 kcal/g (4 kcal/3 g). This means that fatty acids can hold more than six times the amount of energy. Put another way, if the human body relied on carbohydrates to store energy, then a person would need to carry 67.5 lb (31 kg) of hydrated glycogen to have the equivalent energy of 10 lb (5 kg) of fat. Hibernating animals provide good example for utilizing fat reserve as fuel. For example bears go on hibernation for about 7 months and during this entire period the energy is derived from degradation of fat stores.

Ruby-throated Hummingbirds fly non-stop between New England and West Indies (approximately 2400 km) at a speed of 40 km/h for 60 hours. This is possible only due to the stored fat.

Digestion

Fatty acids are usually ingested as triglycerides, which cannot be absorbed by the intestine. They are broken down into free fatty acids and monoglycerides by lipases with the help of bile salts. Most are absorbed as free fatty acids and 2-monoglycerides, but a small fraction is absorbed as free glycerol and as diglycerides. Once across the intestinal barrier, they are reformed into triglycerides and packaged into chylomicrons or liposomes, which are released in the lymph system and then into the blood. Eventually, they bind to the membranes of adipose cells or muscle, where they are either stored or oxidized for energy. The liver also acts as a major organ for fatty acid treatment, processing liposomes into the various lipoprotein forms, namely VLDL, LDL, IDL or HDL.

Degradation

See Fatty acid degradation

Synthesis

See Fatty acid synthesis

Regulation and control

Triacylglyceride lipase (TAG lipase), or hormone-sensitive lipase (HSL), is the enzyme that hydrolyses triacylglycerides to diacylglyceride, releasing free fatty acids from fats (lipolysis). HSL is regulated by the hormones insulin, glucagon, norepinephrine, and epinephrine.

Glucagon is associated with low blood glucose, and epinephrine is associated with increased metabolic demands. In both situations, energy is needed, and the oxidation of fatty acids is increased to meet that need. Glucagon, norepinephrine, and epinephrine bind to the G protein-coupled receptor, which activates adenylate cyclase to produce cyclic AMP. cAMP consequently activates protein kinase A, which phosphorylates (and activates) hormone-sensitive lipase.

When blood glucose is high, lipolysis is inhibited by insulin. Insulin activates protein phosphatase 2A, which dephosphorylates HSL, thereby inhibiting its activity. Insulin also activates the enzyme phosphodiesterase, which break down cAMP and stop the re-phosphorylation effects of protein kinase A.

For the regulation and control of metabolic reactions involving fat synthesis, see lipogenesis.

See also

• Fatty acid synthase
• Essential fatty acid
• List of fatty acid metabolism disorders

References

1. Berg, J.M., et al., Biochemistry. 5th ed. 2002, New York: W.H. Freeman. 1 v. (various pagings).
2. Dr.Mahmoud A.Z (own formula for ATP calculation) 2006

External links

• The chemical logic behind the metabolism of fatty acid

•  • [ e] Lipid metabolism: Lipid metabolism/Fatty acid metabolism
Fatty acid degradation (Lipolysis, Beta oxidation) - Fatty acid synthesis

•  • [ e] Metabolism map

Glucuronate metabolism Pentose interconversion Inositol metabolism Cellulose and sucrose metabolism Starch and glycogen metabolism Other sugar metabolism Pentose phosphate pathway Glycolysis and Gluconeogenesis Amino sugars metabolism Small amino acid synthesis Branched amino acid synthesis Purine biosynthesis Histidine metabolism Aromatic amino acid synthesis Pyruvate decarboxylation Anaerobic respiration Fatty acid metabolism Urea cycle Aspartate amino acid group synthesis Porphyrins and corrinoids metabolism Citric acid cycle Glutamate amino acid group synthesis Pyrimidine biosynthesis   •  • [ e]  All pathway labels on this image are links, simply click to access the article. A high resolution labeled version of this image is available here.