Serum pseudocholinesterase and very-low-density lipoprotein metabolism.

Serum pseudocholinesterase (PChE) was discovered in 1932. Since this protein mimics many of the catalytic properties of acetylcholinesterase, it has traditionally been referred to as PChE, even though its true biological function is unknown. Serum PChE is synthesized in the liver and secreted into the circulation as a sialated glycoprotein. Although no convincing evidence of biological function exists, a significant number of obese and diabetic patients have elevated levels of PChE. The same phenomenon is found in experimental animal models of obesity, diabetes and hyperlipoproteinemia. Streptozotocin-induced diabetic mice showed increased serum PChE activity concomitant with increased serum triacylglycerol and PChE activity declined with treatment. Iso-OMPA, a nontoxic inhibitor of serum PChE, reduced serum and liver triacylglycerols and serum VLDL in streptozotocin-induced rodent diabetes. These findings suggest that PChE may have a role in VLDL metabolism.

Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats.

This study was designed to understand the reasons for the increase in serum pseudocholinesterase activity in diabetes mellitus. Streptozotocin-induced diabetic rats were used for the study. Serum pseudocholinesterase activity increased with the induction of diabetes (381.5 units/l +/- 11.8) compared to the non-diabetic rats (243.1 units/l +/- 7.2). Serum triglycerides, total low density lipoprotein and glycerol also increased concurrently with the development of diabetes. Insulin treatment of the diabetic rats normalized serum glucose concomitant with the reduction of pseudocholinesterase activity, triglycerides, total low density lipoprotein and glycerol. Heparin injection appeared to activate lipoprotein lipase in the diabetic rats by showing a marked fall in serum triglyceride and total low density lipoprotein levels but not in pseudocholinesterase activity. Administration of tetraisopropylpyrophosphoramide a specific pseudocholinesterase inhibitor, inhibited serum and adipose tissue pseudocholinesterase activity by greater than 80% and liver greater than 50%. Concurrent with the inhibition of pseudocholinesterase activity serum triglyceride, low density lipoprotein and glycerol decreased significantly. In normal rats treatment with tetraisopropylpyrophosphoramide also reduced serum lipoproteins markedly, while glycerol only showed a marginal decrease. Glycerol was used as a marker of adipose tissue lipolysis and total low density lipoprotein which is defined as lipoproteins of density less than 1.063 (LDL + VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)

A study of pseudocholinesterase induction in experimental obesity.

Liver pseudocholinesterase (PChE) activity was significantly higher in genetically obese (ob/ob) mice than in lean littermates as early as 23 days after birth. By cytochemical electron microscopy, increased staining for PChE was observed in the rough endoplasmic reticulum of ob/ob mice. Albino mice with different diets showed that high-protein diets produced the greatest increase in PChE activity in the liver compared to carbohydrate or high fat. Mice fed a normal mouse diet ad lib had significantly higher liver PChE activity than those fed a restricted diet of 2 g of a normal mouse chow per day. In albino mice liver PChE activity varied directly with the protein content in the diet. These studies suggest that liver PChE induction is a function of the level of protein in the diet.

A study of fat absorption in cystic fibrosis patients and controls by a rapid micro procedure: a comparison with fecal fat excretion method.

Fat absorption was studied in 11 Cystic Fibrosis patients and 6 controls by measuring a) fecal fat excretion and b) serum turbidity using a nephelometer between 0 and 2 hours after a butter-fat load. Cystic Fibrosis patients showed a mean +/- SEM fecal fat excretion of 21.6 +/- 5.5%, and controls a mean of 2.7 +/- 0.45%, of the dietary fat. The turbidity change expressed as delta turbidity showed a mean value of 1.37 +/- 0.57 in Cystic Fibrosis patients and 31.8 +/- 5.7 in controls. Fecal fat excretion method showed a good negative correlation with the butter fat method. The butter fat absorption method was also compared with fecal fat excretion in rats with induced malabsorption and control rats. The results obtained were comparable to those in the patients. The method described here is rapid and can be performed with small blood volumes and therefore may be suitable to study fat malabsorption in pediatric patients.

Pseudocholinesterase/high-density lipoprotein cholesterol ratio in serum of normal persons and of hyperlipoproteinemics.

The proposed complementary risk factor, pseudocholinesterase/high-density lipoprotein cholesterol ratio, was significantly higher in patients with type IIb and IV hyperlipoproteinemias then in controls. In contrast, the established risk factor, total cholesterol/high-density lipoprotein cholesterol ratio, was significantly higher in patients with type IIa and IV hyperlipoproteinemias. Discriminant analysis indicated that prediction of risk for coronary heart disease on the basis of lipoprotein phenotypes can be improved by about 20% when both the above factors are assessed concurrently. On the basis of earlier studies in humans and animals, we also suggest that the proposed risk factor may provide a better understanding of events leading to enhanced risk for coronary heart disease as a consequence of nutrition and of abnormal metabolism of lipids and lipoproteins.

Pseudocholinesterase in obesity: hypercaloric diet induced changes in experimental obese mice.

Pseudocholinesterase activity is significantly higher in liver and serum, but lower in adipose tissue of genetically obese, diabetic and gold thioglucose treated mice. Similar enzyme changes were also observed in lean mice on a high carbohydrate diet. A marked reduction (40%) in PChE activity occurred in the liver of genetically diabetic mice when starved for 24 h. These observations suggest that pseudocholinesterase induction in the liver and repression in the adipose tissue is affected by excessive caloric intake in obesity. This provides a model to study the biological function of PChE in health and disease.

Serum pseudocholinesterase: high density lipoprotein cholesterol ratio as an index of risk for cardiovascular disease.

A significant increase in the ratio of serum pseudocholinesterase/high density lipoprotein cholesterol (the Complementary Risk Factor ratio) was found in individuals classified as high risk for cardiovascular disease on the basis of the ratio of total cholesterol/high density lipoprotein cholesterol (the Established Risk Factor ratio) compared to the individuals with average and low risks. This Complementary Risk Factor ratio also showed good correlation with serum low density lipoprotein, triglycerides and the Established Risk Factor ratio. These results indicate that serum cholinesterase has a parallel relationship with low density lipoproteins and a reciprocal relationship with high density lipoproteins. We propose that the Complementary Risk Factor ratio may be an additional marker in predicting the risks for cardiovascular disease.

Immunocompetence in obesity.

Thirty-eight % of obese children and adolescents showed a variable impairment of cell-mediated immune responses in vivo and in vitro and reduction of intracellular bacterial killing by polymorphonuclear leukocytes. The obese group had a higher incidence of iron deficiency and moderately lower serum zinc concentrations. Levels of serum immunoglobulins, complement components C3 and C4, and numbers of T and B lymphocytes were comparable in the two groups. Serum triglycerides, cholesterol and lipoproteins were normal in all subjects. Immunologic changes correlated with the presence of subclinical deficiencies of iron and zinc. Therapy with these micronutrients for 4 weeks resulted in improvement in immunologic responses.

A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis.

1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients.

Cholinesterase in the atherosclerotic intima and in fibroblast cultures.

Cholinesterase activity was present in the atheromatous plaque of the rabbit's atherosclerotic aorta. Cholinesterase activity was significantly increased in rat fibroblast cultures grown in the presence of hypercholesterolemic serum. Cholesterol ester synthesis in these cultures was inhibited by neostigmine, a cholinesterase inhibitor.

Histidinemia and infantile autism.

A 10-year-old boy first showed features of infantile autism at age 24 months. Histidinemia was also diagnosed, with histidine blood levels seven times higher than the upper normal values. If the coexistence of autism and histidinemia was not coincidental, histidinemia may have constituted a necessary but not sufficient factor leading to the clinical condition of autism. Other members of the patient's family had high blood levels of histidine, but did not show symptoms that have been related to histidinemia.

Cholinesterase in serum and low density lipoprotein of hyperlipidemic patients.

Cholinesterase activity in the low density lipoprotein fraction of serum is increased in types IIa, IIb and IV hyperlipoproteinemic patients, whereas only types IIb and IV show increases in serum cholinesterase activity. In obese patients, cholinesterase activity is increased both in the serum and low density lipoprotein fraction only when hyperlipidemia is present. Cholinesterase activity is also found to increase in proportion with increases in low density lipoprotein, cholesterol, and triglycerides both in the serum and low density lipoprotein fraction. We suggest on the basis of these findings that cholinesterase has a function in lipid and lipoprotein metabolism.

Serum lipids in hypothyroidism--a re-evaluation.

One hundred and forty-two persons referred for assessment of thyroid function were studied in relation to their thyroid function and fasting serum lipids. Forty-five individuals, who had no family history of thyroid disease, were euthyroid, and were negative for thyroid antibodies formed the control group. The remaining 97 patients were fitted into six groups as follows--euthyroid Hashimoto's thyroiditis, thyroiditis with exagggerated TSH response to TRH, and four groups of increasing grades of thyroid failure based on the level of serum TSH. Only in the two most severely hypothyroid groups was cholesterol significantly elevated as compared with control levels. A graded increase in mean serum triglyceride, was observed as thyroid failure increased; however, values were not different (P greater than 0.05) from the control group. However, partial correlation analysis indicated that serum cholesterol was related to increasing levels of serum TSH and that this dependency was not influenced by age or weight. Although serum cholesterol was related to thyroid function in the study population, it was an insensitive indicator of the metabolic effects of thyroid hormone.

A study of the salivary glycoprotein in cystic fibrosis patients and controls: fucose incorporation and protein pattern.

The incorporation of fucose to glycoprotein acceptors prepared from the saliva of Cystic Fibrosis (CF) patients was compared with the incorporation into acceptors from controls. The CF acceptor glycoprotein incorporated significantly more fucose in the presence of either patients' or control plasma. The fucosyl transferase activity in the patients' plasma was not significantly different from controls. Fucosidase activity was similar also for both groups. The protein bands of the acceptor glycoproteins from the patients' saliva differed from those of the control in number and electrophoretic mobility. On the basis of these studies of fucose incorporation we propose that glycoprotein in the salivary secretion of CF patients are qualitatively different from normal.

Serum cholinesterase: function in lipoprotein metabolism.

Human serum beta-lipoproteins, isolated by percipitation with heparin-calcium mixture, showed cholinesterase activity. The enzyme activity was almost proportional to the lipoprotein concentration. Rats, treated with neostigmine, a cholinesterase inhibitor, showed a significant decrease in serum beta-lipoprotein and in the incorporation of H3-lysine into the lipoprotein compared to untreated controls. The decreased incorporation of H3-lysine into beta-lipoprotein was associated with increased labelling of alpha-lopoprotein. There was no significant difference in the labelling of pre-beta-lipoprotein. We propose that LDL is formed from VLDL in the presence of cholinesterase.

Thymus-dependent lymphocytes and delayed hypersensitivity in low birth weight infants.

The proportion of thymus-dependent (T) lymphocytes in the blood and the ability to mount cutaneous delayed hypersensitivity to a battery of antigens were evaluated in 50 low birth weight (LBW) infants when they were 3 months to 5 years old. There was a significant reduction in the number of T lymphocytes. Delayed hypersensitivity was impaired. The abnormalities were more pronounced in those with persistent growth retardation. It is suggested that continued postnatal depression of cell-mediated immunity in LBW infants may contribute to increased frequency of infections and immunopathological diseases.