Plasma aspirin esterases in normal individuals, patients with alcoholic liver disease and rheumatoid arthritis: characterization and the importance of the enzymic components

Abstract

Abstract. Two enzymes in human plasma capable of hydrolysing aspirin (‘aspirin esterases’) were isolated (by ion exchange and gel chromatography) and characterized, since their activity has been reported to be important in certain disease/therapeutic situations. The optimum pH and calcium concentration for plasma aspirin esterases were 80 and 5 mmol/1 respectively. The main enzymic activity (enzyme ‘C’) was associated with plasma cholinesterases. This component had a Km of 6‐5 mmol/1 for aspirin and a Kmax of 0–27 /imol salicylate/mg protein/min at pH 80 (Ca2+ present). It was not acetylated by aspirin but was inhibited by anti‐cholinesterase agents (eserine, echothiophate) and the neuromuscular blocking agent, decameth‐onium. The other enzymic component in plasma was albumin esterase. The sex difference in aspirin esterase activity in normal individuals previously reported by Menguy and co‐workers [1] was re‐investigated since it appeared that they had employed non‐optimal assay conditions. No significant differences were observed between the sexes in either normal individuals or patients with rheumatoid arthritis when the enzyme was assayed at either pH 7‐4 or the optimal pH of 80 (with Ca2+ added). The plasma albumin esterase activity was, however, markedly depressed in patients with alcoholic liver cirrhosis when assayed at pH 7‐4 and 80. Plasma aspirin esterases were elevated in nine rheumatoid arthritic patients receiving gold salt or D(‐)penicil‐lamine. Aspirin esterase 'C activity was negatively correlated with pain score in the plasma of female but not male rheumatoid arthritics. Also the percentage activation by calcium of aspirin esterase was correlated with the concentration of plasma calcium indicating that small changes in plasma calcium concentration may markedly affect enzymic activity. These results suggest that certain drugs (anti‐cholinesterase agents), disease states (e.g. alcoholic liver cirrhosis) or genetic deficiences (e.g. inactive pseudo‐cholinesterase) may be potentially important in the pharmacological and iatrogenic activities of aspirin.

Erythrocyte and plasma aspirin esterase [letter]

“…The cellular enzyme is probably a 'non specific' esterase whereas the plasma enzyme activity is due to cholinesterase as previously demonstrated by Rainsford et al (1980).…”

“…Rainsford et al (1980) have shown that the main plasma aspirin esterase activity is associated with the plasma cholinesterases.…”

Metabolic Mechanism of Delamanid, a New Anti-Tuberculosis Drug, in Human Plasma

“…Albumin, the most abundant protein in plasma (Theodore, 1996), displays pseudo-enzymatic properties and has been found to catalyze the hydrolysis of numerous compounds, such as cinnamoyl imidazole (Ohta et al, 1983), p-nitrophenyl esters (Means and Bender, 1975;Kurono et al, 1979;Watanabe et al, 2000;Sakurai et al, 2004;Lockridge et al, 2008), olmesartan medoxomil (Ma et al, 2005), carbaryl (Sogorb et al, 2004), aspirin (Rainsford et al, 1980;Liyasova et al, 2010), organophosphate insecticides (Sultatos et al, 1984), and Fig. 8.…”

Aspirin metabolism and efficacy in postoperative dental pain.

“…Although plasma and liver esterases capable of hydrolysing aspirin have not been purified, Rainsford et al (1980) has separated two components from plasma. One component appears to be similar to plasma cholinesterase, and the other is an aryl esterase.…”