Pteridines and Lipid Metabolism

Abstract

Summary The effect of 9 different pteridines on fatty acid incorporation into phospholipids as well as on cholesterol and phospholipid content was compared in vitro using rat liver homogenate, Krebs-Ringer phosphate buffer containing 0.3 % albumin (pH=7.4), fatty acid mixture and glycerol. D-neopterin (5-30 pmol/g) induced an increase of saturated, a decrease of unsaturated fatty acids incorporation into phospholipids and elevated the cholesterol content in samples. The phospholipid amount in samples remained unchanged. Sepiapterin, 7,8-dihydrobiopterin, 5,6,7,8-tetrahydrobiopterin, biopterin, monapterin and 7,8-dihydroneopterin addition to samples induced an inverse relationship: a decrease of saturated, an increase of unsaturated fatty acid, especially arachidonic acid, incorporation into phospholipids and the decrease of cholesterol content in samples. The phospholipid amount in samples remained unchanged or increased. Lipid metabolism was not altered after addition of xanthopterin and isoxanthopterin to samples. It was suggested that neopterin decreased membrane fluidity, prevented cell cycle, induced cell dystrophy and apoptosis, and promoted the cholesterol precipitation while tetrahydrobiopterin, its precursors, biopterin, monapterin and dihydroneopterin increased membrane fluidity, stimulated cell cycle, prevented cholesterol precipitation. The data point to a potential role of increased neopterin concentrations in vivo to support atherosclerosis development and progression whereas the other pteridines may have a protective effect. Moreover, these pteridines can also promote cell transformation.

Role of the Phenylalanine-Hydroxylating System in Aromatic Substance Degradation and Lipid Metabolism in the Oleaginous Fungus Mortierella alpina

“…Mutations in the human PAH gene result in the metabolic disorder known as phenylketonuria (PKU) (67), and PKU patients present with lower concentrations of long-chain polyunsaturated fatty acids (LCPUFA), such as arachidonic acid (AA) and eicosapentaenoic acid, and higher con-centrations of oleic acid 18:1 (31,32). It has also been suggested that the PAH cofactor BH 4 is essential for the desaturation or omega oxidation of long-chain fatty acids and the incorporation of unsaturated fatty acids into phospholipids (33)(34)(35)(36). Significant changes were observed in the concentration of total 6 PUFA and AA in M. alpina grown on PAH inhibitor medium compared to M. alpina grown on medium without inhibitor (Fig.…”

“…However, the molecular mechanism of efficient lipid biosynthesis is still not well understood in oleaginous fungi in general and in M. alpina in particular. PAH and its cofactor BH 4 have been suggested to be essential for lipid metabolism in higher organisms (31)(32)(33)(34)(35)(36), and some amino acid metabolism pathways have been postulated to be involved in fatty acid biosynthesis in oleaginous fungi (37,38). However, the functional significance of the phenylalanine-hydroxylating system in the biosynthesis of lipids and closely related compounds has yet to be fully elucidated.…”

Role of dihydrofolate reductase in tetrahydrobiopterin biosynthesis and lipid metabolism in the oleaginous fungus Mortierella alpina

“…However, the role of alternative NADPH sources in fatty acid synthesis is not well understood. BH 4 has been suggested to be essential for lipid metabolism in higher organisms (Forrest & Van Baalen, 1970;Giovannini et al, 1995;Kaufman, 1967Kaufman, , 1993Moseley et al, 2002;Rudzite et al, 1998). In our previous study, a requirement for BH 4 in phenylalanine hydroxylation has been reported in Mort.…”

“…alpina. In higher organisms, BH 4 is suggested to be essential for lipid metabolism, including the concentration of long-chain PUFAs (LCPUFAs), the desaturation or omega oxidation of LCPUFA and the incorporation of unsaturated fatty acids into phospholipids (Forrest & Van Baalen, 1970;Giovannini et al, 1995;Kaufman, 1967;Kaufman, 1993;Moseley et al, 2002;Rudzite et al, 1998). The function of BH 4 in Mort.…”

Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the oleaginous fungus Mortierella alpina

“…It has been suggested that BH 4 might be essential for the desaturation or omega oxidation of long-chain fatty acids, the conversion of dihydrosphingosine into sphingosine, or in sterol metabolism, but the functional significance of BH 4 and closely related compounds remains to be fully elucidated (Forrest & Van Baalen, 1970;Kaufman, 1967Kaufman, , 1993. The effect of BH 4 on lipid metabolism has been investigated in vitro (Rudzite et al, 1998). BH 4 increases the incorporation of unsaturated fatty acids into phospholipids (particularly arachidonic acid) at the expense of saturated varieties, and it also decreases the cholesterol content, which means that BH 4 may act to increase membrane fluidity, stimulate the cell cycle and prevent cholesterol precipitation.…”