Very Long Chain Fatty Acids

Very Long Chain Fatty Acids • Fatty acids (FAs) are rather diverse in the number of double bonds and in terms of carbon (C) chain-length. Very long-chain fatty acids (VLCFAs) are fatty acids with more than 20 carbons. They are precursors of lipid mediators and also components of cellular lipids like sphingolipids and glycerophospholipids. The mutation in VLCFA metabolizing enzymes encoding genes will result in a series of inherited disorders like ichthyosis, demyelination, myopathy, mental retardation and macular degeneration. With the identification of enzymes associated with VLCFA synthesis and degradation, our knowledge about the function of VLCFAs is increasing accordingly. • All plant cells can produce the essential molecules VLCFAs, which are precursors or components of a large number of specialized metabolites generated in specific cell types. Catalyzed by the fatty acid elongation complex of four core enzymes localized in endoplasmic reticulum, VLCFAs are elongated and two carbon units are added to the growing acyl chain. As these enzymes in Arabidopsis thaliana is identified and characterized, it reveals that three of the four enzymes work as generalists, producing all the VLCFAs needed in all metabolic pathways. The fourth component of the complex is the enzyme response for condensing. This unit determines the specificity and the amount of product being synthesized.

• X-linked adrenoleukodystrophy (X-ALD) is a serious progressive, degenerative genetic disease caused by mutations in the ABCD1 gene, which leads to the defect in a peroxisome enzyme. The lack of this enzyme leads to VLCFA to accumulate in tissues of the body, especially spinal cord, the adrenal glands and white matter of the nervous system. Finally, the myelin sheath that embraces the nerves would be destroyed and results in neurologic problems. Though some of the accumulated VLCFA comes from the diet, most VLCFA result from the elongation of long-chain fatty acids in the body. For example, the accumulation of VLCFA in X-ALD patients is the result of failed degradation of fatty acids, because being lack of one of the proteins responsible for degradation. The degradation of VLCFA occurs in the peroxisome inside the cell, which exist inside all cell types in the body except red blood cells. The protein lacked is ALDP (X-ALD protein), which is essential for the transportation of the VLCFA from the cell into the peroxisome. • Elevated concentration of VLCFA in plasma and tissues are the biomarkers for patients with peroxisomal genetic disorders like X-linked adrenoleukodystrophy (X-ALD). However, it is difficult to quantify these VLCFA simultaneous and most of the detection platforms are laborious and time-consuming. Creative Proteomics has established sensitive, reliable, and accurate GC-MS method for quantification of very long-chain fatty acids.