Relationship between pseudocholinesterase and lipids in hyperlipoproteinaemia

Abstract

The biological r d e of serum pseudocholinesterase (PChE) is enigmatic: the protein is normally detected and defined in terms of its catalytic hydrolysis of choline esters but no necessity for such enzymic activity in serum has ever been demonstrated. However, the now well-established association between obesity and PChE in genetic and dietary animal models (Kutty et a[., 1981, 1983), and also in clinical situations (Cucuianu et al., 1968; Chu et al., 1978), suggests that PChE may play a significant part in the aetiology of coronary heart disease (CHD), a common end-stage consequence of obesity and hyperlipoproteinaemia. Serum was collected after an overnight fast from 66 patients with confirmed C H D (80% males; age 35-60 years) and 83 matched controls. Sixteen of the C H D patients were re-investigated after treatment for 2-3 months with diet, or medication, or both, to reduce serum lipids. Cholesterol and triglycerides were measured by standard methods. Lowdensity lipoprotein (LDL) was measured by a turbidimetric method (Walton & Scott, 1964) that included both LDL and very-low-density lipoprotein (VLDL). PChE was measured with butyrylthiocholine iodide substrate (Dietz et al., 1973). Serum PChE activities in the control (mean = 3.15 pmol of thiocholine/min per ml of serum; S.D. = 0.40) did not differ significantly with age or sex in adult subjects. However, 34 C H D patients (50%) had PChE activities exceeding the control 95th percentile, and all C H D patients’ PChE activities exceeded the control mean (Fig. 1). As expected, 50% of the patients were hypercholesterolaemic and 80% were hypertriglyceridaemic by accepted clinical criteria. Correlation analysis of the combined observations from patients and controls demonstrated that PChE is positively correlated with LDL (r = 0.51) and its associated lipids, cholesterol ( r = 0.48) and triglycerides (r = 0.52). Of even greater potential significance is that 18% of the C H D patients with significantly elevated PChE had normal lipid levels. During treatment, the patients’ PChE activities dropped from 4.7 f 0.34 to 3.9 k 0.26pmol of thiocholinelmin per ml ( I = 10.1) in concert with declines in cholesterol, triglyceride and total LDL levels. Animal models (Kutty et al., 1981, 1983) suggest that excess dietary intake is a major determinant of the PChE levels. Genetically obese (oblob), diabetic (dbldb) and normal mice with gold thioglucose-induced obesity exhibit a marked increase (50-150%) in liver and serum PChE activity when diet is unrestricted. Levels of PChE are almost normal when these hyperphagic animals are maintained on restricted diets. The parallel between these experimental models and hypertrophic obesity in humans is clear. However, the problem remains of non-obese, normolipidaemic C H D patients with significantly elevated serum PChE: what is the aetiology of hyperpseudocholinesterasaemia in these individuals and is non-dietary elevated serum PChE an independent risk factor in susceptibility to atheroscleortic heart disease? How could elevated PChE levels be implicated in atherosclerosis? It is possible that the true function of PChE