Pteridines (Nov 2000)
Impairment of Lipid Metabolism Due to Deficiency of Pyridoxal-5-phosphate and/or Activated Immune system: its Interpretation
Abstract
Impairment of lipid metabolism due to excess metabolite accumulation induced by pyridoxal-5-phosphate (P-5-P)-deficiency and/or stimulated immune system has been studied and interpreted. Decreased amounts of phospholipids as well as deviations in phospholipid classes and fatty acid composition of phospholipids have been demonstrated due to kynurenine accumulation in the blood of P-5-P-deficient cardiovascular patients and white rats as well as in cardiovascular patients with activated immune system identified by an increased neopterin concentration in the blood (dilated cardiomyopathy). The addition of P-5-P to the incubation medium for phospholipid biosynthesis in vitro did not change fatty acid incorporation into phospholipids, whereas it normalised fatty acid incorporation into phospholipids in liver homogenates received from P-5-P-deficient rats: The addition of kynurenine, neopterin and noradrenalin (accumulated m isolated heart tissue after addition of kynurenine and neopterin to incubation medium for isolated heart) to incubation medium for phospholipid biosynthesis in vitro induced an increase of saturated and a decrease of polyunsaturated fatty acid incorporation into phospholipids. These changes in fatty acid incorporation into phospholipids were followed by increased cholesterol concentrations in samples and an increased cholesterol/phospholipid ratio. Our results suggest that these changes in lipids are characteristic for decreased membrane fluidity, depressed cell cycle and lowered possibility of phospholipids to keep cholesterol in solution. P-5-P-deficiency is also accompanied with excess accumulation of homocysteine in the blood. The addition of L-homocysteine to the incubation medium for phospholipid biosynthesis in vitro was followed by inverse changes in fatty acid incorporation into phospholipids when compared with kynurenine, neopterin and noradrenalin. L-homocysteine induced a decrease of saturated and an increase of polyunsaturated fatty acid incorporation into phospholipids. The cholesterol concentration decreased in samples and the cholesterol/ phospholipid ratio decreased, too . These findings suggest that changes in lipids induced by L-homocysteine are characteristic for increased membrane fluidity and stimulated cell cycle. In this study, we have observed a similar effect to L-homocysteine effect when L-homocysteine, L-tryptophan and 5,6,7,8-tetrahydrobiopterin were added to the incubation medium for phospholipid biosynthesis in vitro. The comparison of our results with data from the literature allows to suggest that excess metabolite accumulation due to activated formation and inactivated catabolism of it plays a significant role in quantitative and qualitative changes of lipids, especially phospholipids, and therefore participates in the regulation of membrane fluidity, cell cycle of normal and malignant cells as well as in keeping cholesterol in the state of solution.
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