Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zellweger syndrome: direct, unequivocal evidence for the new, revised pathway of phytanic acid alpha-oxidation in humans

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which accumulates in a number of inherited diseases in human. Because beta-oxidation is blocked by the methyl group at C-3, phytanic acid first undergoes decarboxylation via an alpha-oxidation mechanism. The structure and subcellular localization of the phytanic acid alpha-oxidation pathway have remained enigmatic through the years, although they have generally been assumed to involve phytanic acid and not its CoA-ester. This view has recently been challenged by the findings that in rat liver phytanic acid first has to be activated to its CoA-ester before alpha-oxidation and by the discovery of a new enzyme, phytanoyl-CoA hydroxylase, which converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. We now show that this newly discovered enzyme is also present in human liver. Furthermore, we show that this enzyme is located in peroxisomes and deficient in liver from Zellweger patients who lack morphologically distinguishable peroxisomes, which provides an explanation for the long-known deficient oxidation of phytanic acid in these patients. These results suggest that phytanic acid alpha-oxidation is peroxisomal and that it utilizes the coenzyme A derivative as substrate, thus giving further support in favour of the new, revised pathway of phytanic acid alpha-oxidation.     

Levels of soluble stem cell factor in serum of patients with aplastic anemia

Aplastic anemia (AA) is a rare bone marrow (BM) disorder characterized by an unexplained failure of hematopoietic precursors to proliferate. In vitro growth of AA BM cells can be improved by the addition of the hematopoietic growth factor SCF (stem cell factor), which suggests that deficiency of SCF may be one of the underlying causes of the disease. In this study, we measured the concentration of SCF in sera of patients with severe AA. One hundred twenty-eight serum samples from 32 patients, at diagnosis and following therapy, were analyzed. Before treatment, SCF levels varied between 0.33 and 6.1 ng/mL; no correlation between hematopoietic function and SCF serum levels was apparent. Therapy with antilymphocyte globulin (ALG) or bone marrow transplantation (BMT) did not result in a recognizable pattern of changes in SCF levels. However, serum concentration of SCF in many patients with AA was at the low range of control serum levels determined in healthy blood donors. Of 128 AA serum samples tested before and after therapy, 107 were below the mean normal value of 3.3 ng/mL, including 26 samples below the minimum normal value of 1.3 ng/mL, as estimated in 267 controls. We also found that SCF levels in peripheral blood serum correlate well with factor concentrations in the BM plasma. Clinical observations suggest that higher SCF serum levels are often associated with a better clinical status of the patients in terms of survival and transfusion requirements. The data indicate that a deficient production of soluble SCF may contribute to AA in some patients; thus, suggesting a potential therapeutic benefit of SCF in this disorder.     

Thermodynamic properties of magnesium-lead alloys

Magnesium activities in liquid magnesium-lead alloys have been measured with electromotive force cells over the temperature range 745 to 868 K and over the mole fraction range 0.03 <X _Mg<0.50. The exper imental data were used to evaluate the parameters in the empirical temperature-composition relationship proposed by Krupkowski for describing the activity coefficients. Values generated from the Krupkowski formulae were utilized with data for liquidus compositions to evaluate the free energies of formation of the solid intermediate phases and compared with available experimental data for Mg₂Pb.     

Flavor and oxidative stability of northern-grown sunflower seed oil

Flavor and oxidative stabilities of a northern-grown sunflower seed oil were investigated. Taste panel and oxidative evaluations were made on alkali-refined, deodorized, unbleached samples treated with commercial antioxidant mixtures, phenolic antioxidants, metal scavengers and added trace metals. Similar evaluations were conducted on a sample of the same oil after bleaching. Commercial antioxidant mixtures containing both phenolic antioxidants and a metal scavenger improve the flavor and oxidative stabilities of refined unbleached oil. Although phenolic antioxidants alone improve oxidative stability as measured by the active oxygen method test, flavor stability did not improve significantly for antioxidant-treated refined, unbleached samples after accelerated storage. Conversely, alkali-refined and bleached sunflower oil responded to treatment with certain phenolic antioxidants. Although iron and copper are deleterious to oil stability at concentrations of 0.1 ppm, such metal-inactivating agents as citric acid are effective in improving flavor stability. N. Market. Nutr. Res. Div., ARS, USDA.