HUMAN SERUM, CYSTEINE AND HISTIDINE INHIBIT THE OXIDATION OF LOW-DENSITY-LIPOPROTEIN LESS AT ACIDIC PH

Low concentrations of serum or interstitial fluid have been shown to i nhibit the oxidation of low density lipoprotein (LDL) catalysed by cop per or iron, and may therefore protect against the development of athe rosclerosis, As atherosclerotic lesions may have an acidic extracellul ar pH, we have investigated the effect of pH on the inhibition of LDL oxidation by serum and certain components of serum. Human serum (0.5%, v/v), lipoprotein-deficient human serum at an equivalent concentratio n and the amino acids L-cysteine (25 mu M) and L-histidine (25 mu M), but not L-alanine (25 mu M), inhibited effectively the oxidation of LD L by copper at pH 7.4, as measured by the formation of conjugated dien es, The antioxidant protection was reduced considerably at pH 6.5, and was decreased further at pH 6.0. These observations may help to expla in why LDL becomes oxidised locally in atherosclerotic lesions in the presence of the strong antioxidant protection offered by extracellular fluid. (C) 1998 Federation of European Biochemical Societies.