Fatty acids are fuel molecules that yield large amounts of energy when degraded in a series of reactions in the mitochondria. Other important functions of fatty acids include:
1) serving as building blocks of phospholipids and glycolipids:
2) acting (as derivatives) as hormones and intracellular messengers:
3) modfying proteins through covalent attachment, and so affecting their cellular targeting and functioning.
Fatty acids contain a long hydrocarbon chain and a terminal carboxylate group. Most contain between 14 and 24 carbon atoms. The chains may be saturated or contain double bonds. The complete oxidation of fatty acids yields about 9 kcal/g, which is over 2 times the energy that can be obtained from the same weight of carbohydrate.
Fatty acid catabolism is initiated when triacylglycerol (in adipose tissue) is hydrolyzed by lipases. Lipases are activated when high levels of cyclic AMP stimulate protein kinase A to phosphorylate the lipase. This reaction yields 3 fatty acids and glycerol. The fatty acids are then transported to tissues for oxidation.
Inside these tissues, before fatty acids can be oxidized, they must be attached to coenzyme A. This reaction is driven by ATP and is catalyzed by acyl CoA synthase, in the cytosol.
Fatty acids are oxidized inside the mitochondria where the beta-oxidation system is located. The translocation of fatty acids (as acyl-CoA molecules) from outside of the mitochondria to the inside is accomplished by joining the the acyl broups to carnitine. The fatty acid is able to cross as an acylcarnitine ester. Once inside the mitochondrion, the acyl-CoA form is regenerated, ready for beta-oxidation. A deficiency of carnitine or the carnitine palmitoyltransferase (CPT) would limit this process. A common symptom is cramping in the muscles.
The degradation of fatty acids occurs in 4 reactions:
In each reaction cycle the fatty acid is shortened by 2 carbon atoms, with one FADH2, NADH, and acetyl CoA being formed. The acetyl CoA can then enter the TCA cycle, to generate energy (ATP), while the NADH and FADH2 can be used in oxidative phosphorylation to generate more ATP.
Back to Intro to Carnitine Deficiency
Back to Clinical Cases in Carnitine Deficiency