Phytanic

Phytane is a naturally occurring alkane produced by the alga Spirogyra and is a constituent of petroleum The lUPAC name for phytane is 2 6 10 14 tetramethylhexadecane Write a structural formula for phytane... 

Although /3-oxidation is universally important, there are some instances in which it cannot operate effectively. For example, branched-chain fatty acids with alkyl branches at odd-numbered carbons are not effective substrates for /3-oxidation. For such species, a-oxidation is a useful alternative. Consider phy-tol, a breakdown product of chlorophyll that occurs in the fat of ruminant animals such as sheep and cows and also in dairy products. Ruminants oxidize phytol to phytanic acid, and digestion of phytanic acid in dairy products is thus an important dietary consideration for humans. The methyl group at C-3 will block /3-oxidation, but, as shown in Figure 24.26, phytanic acid a-hydroxylase places an —OFI group at the a-carbon, and phytanic acid a-oxidase decar-boxylates it to yield pristanie add. The CoA ester of this metabolite can undergo /3-oxidation in the normal manner. The terminal product, isobutyryl-CoA, can be sent into the TCA cycle by conversion to succinyl-CoA. 

The a-oxidation pathway is defective in Refsum s disease, an inherited metabolic disorder that results in defective night vision, tremors, and other neurologic abnormalities. These symptoms are caused by accumulation of phytanic acid in the body. Treatment of Refsum s disease requires a diet free of chloro-... 

FIGURE 24.26 Branched-chain fatty acids are oxidized by o -oxidation, as shown for phytanic acid. The product of the phytanic acid oxidase, pristanic acid, is a suitable substrate for normal /3-oxidation. Isobutyryl-CoA and propionyl-CoA can both be converted to suc-cinyl-CoA, which can enter the TCA cycle. 

Phytanic acid, the product of chlorophyll that causes problems for individuals with Refsum s disease, is 3,7,11,15-tetramethyl hexa-decanoic acid. Suggest a route for its oxidation that is consistent with what you have learned in this chapter. Hint The methyl group at C-3 effectively blocks hydroxylation and normal /3-oxidation. You may wish to initiate breakdown in some other way.)... 

Identification becomes more difficult in the case of isoparaffins since many structural isomers are possible with increasing carbon number. Nevertheless, all possible isoalkanes from through have been found in crude oils, along with several isomers of and some of Many isoprenoids (e.g., pristane and phytane) which serve as biomarkers to the genesis of petroleum have been detected in significant... 

Schluter, A. et al.. The chlorophyll-derived metabolite phytanic acid induces white adipocyte differentiation, Int. J. Obes., 26, 1277, 2002. 

Arnhold, T, Ehnazar, M.M.A., and Nau, H., Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all frara-retinoic acid, Toxicol. Sci., 66, 274, 2002. 

Lipids from marine products have been studied less frequently. The detection of co-(o-alkylphenyl)alkanoic acids with 16,18 and 20 carbon atoms together with isoprenoid fatty acids (4,8,12-trimethyltetradecanoic acid and phytanic acid) and substantial quantities of bones from fish and molluscs has provided evidence for the processing of marine animal products in vessels [58 60]. C16, C18, and C20 co-(o-alkylphenyl)alkanoic acids are presumed to be formed during the heating of tri-unsaturated fatty acids (C16 3, C18 3 and C20 3), fatty acyl components of marine lipids, involving alkali isomerization, pericyclic (intermolecular Diels-Alder reaction) and aromatization reactions. 

Isoprenoid fatty acids (4,8,12 trimethyl tetradecanoic acid and phytanic acid), acids with 16, 18 and 20 carbon atoms Heated marine lipids [42,43]... 

Another relevant feature of the gas chromographic profile is the acyclic isoprenoid hydrocarbon pattern that is made evident with capillary columns or by the inclusion of the saturated fraction in 5 A (0.5 nm) molecular sieves or in urea. The predominant peaks usually correspond to the C19 (pristaine) and C20 (phytane) isomers, which ratios serve as an identification parameter [87], although the series extends to lower and higher homologues. 

Refsum s disease is an autosomal recessive peroxisomal disorder characterized by accumulation of phytanic acid and other 3-alkyl-branched fatty acids [55]. Patients develop hypertrophic demyelinative polyneuropathy, retinitis pigmentosa, ichthyosis and deafness. The disorder can be successfully treated by institution of a diet poor in phytanic acid, in conjunction with plasmapheresis to remove circulating phytanic acid. 

Refsum s disease AR Oxidation of branched chain fatty acids phytan-olyl CoA 2-hydroxylase in some cases Increase of branched-chain phytanic acid, especially in PNS myelin 1, 38, Ch. 40... 

Refsum s disease. This disorder, first described nearly 60 years ago, was recently been shown due to a defect in the enzyme phytanoyl-CoA hydroxylase. Phytanic acid is a 3-methyl fatty acid that because of this methyl group cannot be oxidized directly. It is degraded by a peroxisomal a-oxidation to pristanic acid, a 2-methyl fatty acid which can be degraded by P-oxidation. The principal clinical features of Refsum s disease are progressive polyneuropathy, retinal degeneration, hearing loss, cardiomyopathy and ichthyosis, beginning in late childhood or later. 

Most, and possibly all of these changes result from the tissue accumulation of phytanic acid. Phytanic is of dietary origin exclusively, and dietary restriction of phytanic and plasmapheresis are of clinical benefit. The defective gene and pathogenic mutations have been identified. The clinical manifestations can also be mimicked by defects of PEX7. 

The isoprenoid hycrocarbons pristane and phytane (derived from the phytol side chain of chlorophyll), as well as porphyrins, have been detected in organic extracts of the Nonesuch Shale of 1.1 billion year age [23]. Their presence points to the existence of photosynthetic pigments in the Precambrian era, but it is also possible that these extractable substances could have been contributed to the rock at a later time. However, in this instance contamination appears to be less likely on account of the large abundance of organic material in this shale. 

Physiological functions, of vitamins, 25 784 Physiology, of ascorbic acid, 25 766-773 Physisorbed water, 23 71-72 Physostigmine, 2 817-818 Phytane, 18 592... 

Figure 7.12 Potential biomarkers in bitumen the isoprenes (a) pristane (Ci9H40) and (b) phytane (C2oH42), and (c) the hopane 17o (H), 21/3(H)-pentakishomohopane (22R).

Tsai, Su-Chen, Steinberg, D., Avigan, J., Fales, H. M. Studies on the stereospecificity of mitochondrial oxidation of phytanic acid and of a-hydroxyphytanic acid. J. Biol. Chem. 248, 1091-1097 (1973). 

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