Phytanic acid structure

Hay and Morrison (1971) later presented additional data on the fatty acid composition and structure of milk phosphatidylethanolamine and -choline. Additionally, phytanic acid was found only in the 1-position of the two phospholipids. The steric hindrance presented by the four methyl branches apparently prevents acylation at the 2-position. The fairly even distribution of monoenoic acids between the two positions is altered when the trans isomers are considered, as a marked asymmetry appears with 18 1 between the 1- and 2-positions of phosphatidylethanolamine, but not of phosphatidylcholine. Biologically, the trans isomers are apparently handled the same as the equivalent saturates because the latter have almost the same distribution. There are no appreciable differences in distribution of cis or trans positional isomers between positions 1 and 2 in either phospholipid. Another structural asymmetry observed is where cis, cis nonconjugated 18 2s are located mostly in the 2-position in both phospholipids. It appears that one or more trans double bonds in the 18 2s hinders the acylation of these acids to the 2-position. 

Cushley, R. J., Forrest, B. J., Gillis, A., Tribe, J. (1981). Structures and properties of mixtures of branched chain compounds and lecithin Phyto, a-tocopherol (vitamin E), and phytanic acid, Photochem. Photobiol, 34 458. 

Recent studies have led to a full resolution of the structure of the phytanic acid a-oxidation pathway. Indeed independent studies by Croes et aC and Verhoeven revealed that 2-hydrox5 hytanoyl-CoA undergoes cleavage to produce formyl-CoA and pristanal respectively, which is than oxidized to pristanic acid (Fig. 3B). The pristanic acid is now ready for p-oxidation after its activation to its CoA-ester. 

Fig. 6.24 Structures of substrate complexes of M. tuberculosis P450s. Expanded structural views of the active site regions ( upper panel) and close-up views of the active site cavity organization (lower panel) of the CYP125A1 complex with cholest-4-en-3-one (a) (PBD 2X5W) [363] the CYP124A1 complex with phytanic acid (b) (PDB 2WM4) [395] and the CYP121A1 complex with cYY (c) (PDB 3G5F) [65], Selected amino acids involved in substrate binding are shown in stick representation, color coded as in Fig. 6.1. The substrates are shown in atom colored sticks with cyan carbons...

The cause of the disease is not known. By analogy with other storage diseases, it is suspected that accumulation of phytanic acid is closely related to the basic cause of HAP. Since lipids are important for the structure and function of the nervous system, it is likely that the morphologic changes observed are related to the appearance of the atypical lipid. However, the abnormalities are not specific similar polyneuritic changes are seen in disorders where phytanic acid does not play any role. 

The mechanism by which accumulation of phytanic acid may produce the features of the disease is not known. The possibility of competitive depression of another, essential fatty acid is not supported by available data low concentrations of acids, such as linoleic or other polyenoic acids are relative rather than absolute when the increase in total lipid content of involved organs is considered. It is possible that certain effects result from the particular molecular structure of phytanic acid, since it possesses four methyl groups and is considerably less polar than acids of similar chain length (palmitic) on one hand and the straight chain fatty acids with the same number of carbon atoms (C-20, eicosanoic acid) on the other. The methyl groups rather than the carboxyl group may determine the behaviour of the acid and its interactions, for instance, with membrane lipids of nerves or with the conducting system. 

Figure 1 Fatty-acid structure and nomenclature. (A) Chemical formula and carbon atom numbering system for a 16-carbon saturated fatty acid (16 0). (B) Schematic representation of 16 0. (C) A monounsaturated fatty add, 18 1n-9, showing the double bond nine carbon atoms from the methyl end (carbon 18). (D) The essential n-6 fatty acid 18 2n-6, where the first double bond is found six carbon atoms from the methyl end. The two double bonds are separated by a methylene (-CH2-) group. (E) The essential n-3 fatty acid 18 3n-3, where the first double bond is found three carbon atoms from the methyl end. (F) Phytanic acid, a dietary / -methyl-branched-chain fatty acid (3,7,11,15-tetramethyl 16 0). The melhyl group on carbon 3 prevents this fatty acid from degradation by /3-oxidation. (G) Pristanic acid (2,6,10,14-tetramethyl 15 0) is the product of phytanic acid o-oxidation, in which a single carbon (carbon 1) is lost. The methyl group on carbon 2 does not preclude subsequent degradation by /3-oxidation.

Structurally, phytanic acid is related to farnesyl pyrophosphate, a precursor of steroid biosynthesis. If a molecule of farnesyl pyrophosphate, formed by the condensation of three molecules of isopentenyl pyrophosphate... 

Several inborn errors of metabolism exist in which the missing enzyme is one that is involved in the breakdown of a specific lipid molecule. Since the biosynthesis of these lipids is not impaired, the result of the enzyme deficiency is the gradual accumulation of lipids in the tissues. Most of the important diseases of this type are ones that involve structural lipids, frequently glycosphingolipids, of the central nervous system and they are summarized in Table 8.8. The diseases are rare and frequently fatal, which serves to indicate how important it is that the amounts and types of lipids in membranes are strictly controlled to preserve biological function. Many of the lipids involved in these disorders are readily synthesized in the body, so that dietary treatment is ineffective. There is one lipid storage disease, Refsum s disease, however, that can be controlled by strict exclusion of a fatty acid from the diet. This disease is due to a failure to break down by a-oxidation, the branched chain fatty acid, phytanic acid (Figure 8.12), which is formed from phytol, a universal constituent of green plants. In patients, there is a characteristic build-up of phytanic acid in the blood where it may represent 30% of the total fatty acids. A condition of ataxic neuropathy develops and the disease is normally fatal. To survive, the patients must have a low phytol diet. 

Only a few major compound series can be recognized at the level of their molecular structures based on relative retention times and distribution patterns by gas chromatography alone. This applies to n-alkanes in the nonaromatic hydrocarbon fraction, n-fatty acids in the carboxylic acid fraction and in some cases n-alkanols in the neutral polar fraction. High abundance of a few single compounds (pristane, phytane, long-chain alkenones) sometimes also allow their direct identification from gas chromatograms. 

When the four sldechaln methyl groups of phytanic or dlhydrophytanlc acid are Incorporated Into lipid bllayer structures their stability Is greatly reduced. The myelin Is broken and no longer an effective insulator for the neuroelectrical activity of mammalian nerves. For this reason we have active alpha oxidase in our brain which we should use to express our appreciation to Paul Stumpf and his avocados and peanuts. 

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