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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.

Blood serum neopterin, high sensitivity C-reactive protein (hsCRP), total homocysteine, pyridoxal-5-phosphatc ( P-5-P) and total phospholipid concentrations have been examined in 30 healthy individuals as well as in patients with coronary artery disease (CAD) verified by coronary angiography (43 patients with 1-artery disease, 24 patients with 2-or 3-artery disease, 17 patients with restenosis) before percutaneous transluminal coronary angioplasty. We have observed increased mean concentrations of neopterin, hsCRP and homocysteine as well as decreased mean concentration of P-5-P and phospholipids in all groups of CAD patients. The positive correlation between neopterin and hsCRP in all CAD patients (r = 0.536; Ρ <0.01 ) as well as an increased frequency of these indices above the upper limit of normal during the course of CAD (30.1 % in eases with 1-artery disease, 54.2% of cases in 2-or 3-artery disease, 76.5% of cases in restenosis) allow to conclude that inflammation has a pivotal role in the progression of CAD. In restenosis the determination ot neopterin was of more significance than the determination of hsCRP. The combination of a mild increase of neopterin and homocysteine concentrations points to the worst prognosis of CAD, both after percutaneous transluminal coronary angioplasty and coronary bypass, restenosis was most liekly to appear. Mild increase of homocysteine concentration in patients with CAD docts not only indicate possible thickening of arterial wall and narrowing of lumen but also to impaired trans-sulfuration and remethylation pathways of homocysteine metabolism as well as to delayed methylation processes in the organism. A decrease of serum P-5-P concentration, which in all groups of CAD patiens reached about 50% as compared with healthy individuals, points to impairment of all metabolic processes, which require the biologically active form of vitamin B6 for their action. The decrease of mean serum phospholipid concentration in all groups of CAD patients may indicate both, impaired phospholipid biosynthesis due to delayed processes of methylation in the organism and increased loss of phosphatidylcholine necessary for transportation of oxidised low density lipoproteins into macrophages. Therefore the determination of serum phospholipid concentration and phosphatidylcholine concentration, especially, has the same significance in the course of CAD as the determination of total cholesterol, high and low density lipoprotein cholesterol widely used at present.

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