Fatty acid metabolism

Overview

• lipases.
• Once freed from glycerol, free fatty acids can enter blood and muscle fiber by diffusion.
• 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 propionyl-CoA 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 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 energy equivalent to 10 lb (5 kg) of fat.   Hibernating animals provide a good example for utilizing fat reserves as fuel. For example, bears hibernate 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 and Transport

Fatty acids are usually ingested as LDL receptors. This provides a mechanism for absorption of LDL into the cell, and for its conversion into free fatty acids, cholesterol, and other components of LDL.

When blood sugar is low, serum albumin transports fatty acids to organs such as muscle and liver for oxidation when blood sugar is low.

Degradation

Main article: Fatty acid degradation

Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, resulting in release of energy to the target cells. It includes three major steps:

• Lipolysis of and release from adipose tissue,
• Activation and transport into mitochondria,
• β-oxidation

Synthesis

See Fatty acid synthesis

Regulation and control

It has long been held that hormone-sensitive lipase (HSL) is the enzyme that hydrolyses triacylglycerides to free fatty acids from fats (lipolysis). However, more recently it has been shown that at most HSL converts triacylglycerides to monoglycerides and free fatty acids. Monoglycerides are hydrolyzed by monoglyceride lipase; adipose triglyceride lipase may have a special role in converting triacylglycerides to diacylglycerides, while diacylglycerides are the best substrate for HSL.^[1]. HSL is regulated by the hormones 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 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 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. ^ Zechner R., Strauss J.G., Haemmerle G., Lass A., Zimmermann R. (2005) Lipolysis: pathway under construction. Curr. Opin. Lipidol. 16, 333-340.

Berg, J.M., et al., Biochemistry. 5th ed. 2002, New York: W.H. Freeman. 1 v. (various pagings).

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