Fatty acids, binding protein desaturation

Several studies have evaluated the effects of oral di(2-ethylhexyl) adipate on various aspects of hepatic lipid metabolism. Feeding di(2-ethylhexyl) adipate (2% of diet) to male Wistar rats for seven days resulted in increased hepatic fatty acid-binding protein as well as in increased microsomal stearoyl-CoA desaturation activity (Kawashima et al., 1983a,b). Feeding the compound at this dose for 14 days resulted in increased levels of hepatic phospholipids and a decline in phosphatidyl-choline phosphatidylethanolamine ratio (Yanagita et al., 1987). Feeding di(2-ethyl-hexyl) adipate (2% of diet) to male NZB mice for five days resulted in induction of fatty acid translocase, fatty acid transporter protein and fatty acid binding protein in the liver (Motojima et al., 1998). 

Kawashima, Y., Nakagawa, S., Tachibana, Y. Kozuka, H. (1983a) Effects of peroxisome proliferators on fatty acid-binding protein in rat liver. Biochim. biophys. Acta, 754, 21-27 Kawashima, Y, Hanioka, N., Matsumura, M. Kozuka, H. (1983b) Induction of microsomal stearoyl-CoA desaturation by the administration of various peroxisome proliferators. 

The EFA metabolism is presented in several extensive reviews.9 16 17 Much of the information concerning EFA physiology and biochemistry has been derived from work in hepatocytes and may be of limited relevance to epidermis since a major role of the liver is to convert dietary lipids into energy stores. Meanwhile, keratinocytes are involved in the fatty acid metabolism required both for normal cellular processes and the specialized role in the permeability barrier. Unlike the liver, the epidermis does not possess the capacity to desaturate at the A5 or A6 position, and therefore the skin relies on a supply of AA, LA, and ALA from the bloodstream. There is evidence for a distinct fatty acid binding protein in keratinocyte plasma membranes that is involved in EFA uptake into the skin and also recycling of free fatty acids from the stratum corneum.18 The transport mechanism in epidermis differs from that in hepatocytes since there is preferential uptake of LA over OA, which may function to ensure adequate capture of LA for barrier lipid synthesis.18... 

The active site similarities listed above belie a remarkable functional diversity, which includes phosphate ester hydrolysis, dioxygen and NO reduction, reversible O2 binding, and O2 activation, the last of which includes enzymes involved in ribonucleotide reduction, hydrocarbon monooxygenation, and fatty acyl desaturation. At the overall protein level, the purple acid phosphatases (PAPs) seem to be completely unrelated, both structurally and functionally, to any of the others in this class. Similarly, the flavo-diiron enzymes form a structurally and probably functionally distinct family of proteins, catalyzing both dioxygen and NO reduction. These last two examples illustrate that attempts to shoehorn all of these enzymes into a single class can sometimes provide a simplistic and misleading view of their chemistry and biochemistry. 

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