Fatty acid human disorders

A method for quantitative acylcamitine profiling in human skin fibroblasts using unlabelled palmitic acid diagnosis of fatty acid oxidation disorders and differentiation between biochemical phenotypes of MCAD deficiency. 

In humans, several genetic disorders of fatty acid catabolism, such as the most common MCAD-deficiency, have been reported but their description falls beyond the scope of this review. Several recent reviews have described many of these diseases and their symptoms in more detail (Longo et al., 2006 Rinaldo et ah, 2002 Wanders and Waterham, 2006 Yang et ah, 2005). For mitochondrial fatty acid oxidation disorders the symptoms often develop at infancy during an episode of increased energy demand such as fasting, exercise or illness. Peroxisomal fatty acid oxidation enzyme deficiencies often involve neuropathy and retinopathy. 

Wanders, R. J. A., Komen, J., Kemp, S. (2011). Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans. FEES Journal, 278(2), 182-194. doi 10.1111/j. 1742-4658.2010.07947.X... 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

In summary, these varied therapeutic strategies for using NO and fatty acids have potential for usefulness in human disease. The examples given are for cancer, but the potential extends to a variety of other human disorders. 

More than 20 other human genetic defects in fatty acid transport or oxidation have been documented, most much less common than the defect in MCAD. One of the most severe disorders results from loss of the long-chain /3-hydroxyacyl-CoA dehydrogenase activity of the tri-functional protein, TFP. Other disorders include defects in the a or /3 subunits that affect all three activities of TFP and cause serious heart disease and abnormal skeletal muscle. ... 

The antiscurvy (antiscorbutic) activity was called vitamin C, and when its structure became known it was called ascorbic acid. The fat-soluble factor preventing rickets was designated vitamin D. By 1922, it was recognized that another fat-soluble factor, vitamin E, is essential for full-term pregnancy in the rat. In the early 1930s vitamin K and the essential fatty acids were added to the list of fat-soluble vitamins. Study of the human blood disorders "tropical macrocytic anemia" and "pernicious anemia" led to recognition of two more water-soluble vitamins, folic acid and vitamin B12. The latter is required in minute amounts and was not isolated until 1948. Have all the vitamins been discovered Rats can be reared on an almost completely synthetic diet. However, there is the possibility that for good health humans require some as yet undiscovered compounds in our diet. Furthermore, it is quite likely that we receive some essential nutrients that we cannot synthesize from bacteria in our intestinal tracts. An example may be the pyrroloquinoline quinone (PQQ).e... 

Stallberg-Stenhagen S, Svennerhohn L. Fatty acid composition of human brain sphingomyelins. Normal variation with age and changes during myelin disorders. J. Lipid Res. 1965 6 146-155. 

Intake of dietary sources of n-3 fatty acids is associated with reduced incidence and severity of inflammatory disorders, cardiovascular diseases, and some cancers in humans (12, 98-103). Populations consuming fish that are rich in n-3 fatty acids are known to have a low incidence of atherosclerotic disorders (104). Dietary fish oil, which is high in EPA and DHA, also was shown to reduce myocardial ischemic damage (105) and ventricular fibrillation (106). The antitumorigenic effect of n-3 fatty acids was demonstrated in breast cancer (107), colon cancer (108-110), and pancreatic neoplasm (111). In addition to their beneficial influence on cardiovascular disorders and cancers, n-3 fatty acids are also known to decrease the severity and minimize symptoms of inflammatory diseases, including rheumatoid arthritis (15) and inflammatory bowel disease (16), and may be of benefit in correcting psychological disorders (17). 

Numerous animal and human studies suggest that dietary cholesterol and certain saturated fatty acids increase serum as well as LDL-cholesterol concentrations. Even though humans with elevated serum cholesterol levels may be at risk, evidence also is mounting to suggest that the complicated processes that occur during atherosclerosis involve not only the participation of modified lipoproteins, but also low level and chronic inflammation and related disorders of the immune... 

Wanders RJ, Ijlst L, Poggi F, Bonnefont JP, Munnich A, Brivet M, et al. Human trifimctional protein deficiency a new disorder of mitochondrial fatty acid beta-oxidation. Biochem Biophys Res Commun 1992 188 1139-45. 

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