Overview:

Fatty acids are an important fuel for energy production in most cells and in particular for heart and skeletal muscle. The presence of free fatty acids in the circulatory system of mammals, coupled with insulin levels, determines whether a given tissue uses glucose or fatty acids to derive electrons for cellular respiration. The currency of electron transfer from fatty acids is acetyl coenzyme A which is metabolized by the Krebs Cycle to provide NADH for oxidative phosphorylation. There is one remarkable exception to the above, the brain is unable to use fatty acids but must instead rely on glucose or on ketone bodies as a source of energy for ATP production.

As a reminder, acetyl CoA has other cellular functions besides in energy metabolism. This compound is the substrate for an important and only recently discovered signaling mechanism in cells, the reversible acetylation of proteins. Acetylation using acetylCoA as substrate, is catalyzed by a class of enzymes called histone acetyltransferases (HATs), e.g. p300, which have now been proven to react with many cellular proteins besides histones. Deacetylation is catalyzed by a novel set of proteins called the sirtuins. Although not fully explored, the levels of acetylCoA, and indirectly the levels of fatty acids, are likely to affect this signaling process and hence overall cellular homeostasis.

Dietary fatty acids are diverse, depend on food source, and include saturated and unsaturated fatty acids of different chain lengths as well as branched chain and omega fatty acids. Beta fatty acid oxidation occurs within mitochondria and begins with entry of the fatty acid into the organelle linked to carnitine via the transporters CPT1 and CPT2. Initial chain shortening involves a set of acylCoA dehydrogenases that react specifically with substrates of different chain length e.g. very long chain, long chain, medium chain and short chain isoforms. Further processing involves the enzymes shown in a simplified pathway diagram (click the thumbnail to the right).

Several forms of fatty acids are processed prior to uptake into mitochondria. This takes place predominantly in the peroxisome and to a lesser extent in the endoplasmic reticulum. More information on peroxisomal fatty acid is provided here.

There are several inherited disorders of fatty acid metabolism, the most common of which is MCAD deficiency. The ability to utilize fatty acids as fuel and the regulation of this process relative to use of glucose is at the heart of diabetes, metabolic disorders and is a factor in cancer. This notwithstanding, the antibodies available for and assays of activity of the various fatty acid oxidation enzymes have been sparse until now. MitoSciences has recently released a set of mAbs to a majority of the key enzymes of the fatty acid pathway (both mitochondrial and peroxisomal) that are provided in combinations for screening the relative levels of the different enzymes. The levels of many of the key fatty acid oxidation enzymes are expected to be sensitive to diet, exercise and to various drug treatments, particularly ones for controlling diabetes and metabolic syndrome.

Selected Readings:

Houten SM, Wanders RJ. A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation. J Inherit Metab Dis. 2010 Mar. (Epub ahead of print)

Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010 Jan;90(1):207-58.

Moczulski D, Majak I, Mamczur D. An overview of beta-oxidation disorders. Postepy Hig Med Dosw (Online). 2009 Jun;63:266-77.

Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E578-91.

Cat. No.	Name	Reactivity	Apps.	Amount	Price
MS722	CPT2 antibody	human, rat, mouse, bovine	ICC, IP, ICE	100 µg	$325.00
MS711	DECR1 antibody	human	ICC, IHC, IP, ICE	100 µg	$325.00
MS782	ETF subunit alpha (ETFA) antibody	human, mouse, rat	WB, ICC, IP, ICE	100 µg	$325.00
MS726	MCAD antibody	human, bovine, rat, mouse	WB, ICC, IHC, IP, ICE	100 µg	$325.00
MS706	SCHAD antibody	human	ICC, IHC, IP, ICE	100 µg	$325.00
MS702	TFP subunit alpha (HADHA) antibody	human	WB, ICC, IP, ICE	100 µg	$325.00
MS733	TFP subunit beta (HADHB) antibody	human	WB, ICC, IP, ICE	100 µg	$325.00
MS734	TFP subunit alpha and beta (HADHA / HADHB) IHC antibody	human, bovine, rat	ICC, IHC, IP	100 µg	$325.00
MS707	VLCAD antibody	human, mouse, rat, bovine	ICC, IHC, IP	100 µg	$325.00	<

Cat. No.	Name	Reactivity	Amount	Price
MSX32	MetaPath™ Fatty Acid Oxdiation 4-Plex Dipstick Array	human	30 tests	$545.00
			90 tests	$995.00