(from OMIM) Markey et al. (1987) studied monocyte esterase activity in 1,000 doctor-attending patients with normal hematologic indices and in 56 patients with non-Hodgkin lymphoma (NHL; see 605027) or B-cell chronic lymphocytic leukemia (CLL). The incidence of esterase deficiency was significantly greater in the NHL-CLL patients (7.1%) than in the population group (1.7%). Study of the families in the NHL-CLL group showed that the esterase deficiency was a familial characteristic. There were 2 instances of apparent male-to-male transmission_a man with NHL and the deficiency had a sister and brother with the deficiency and their father also had the deficiency. Bell et al. (1992) described familial monocyte esterase deficiency in 4 patients with rheumatoid arthritis.
References
Title: Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase Becker A, Bottcher A, Lackner KJ, Fehringer P, Notka F, Aslanidis C, Schmitz G Ref: Arterioscler Thromb, 14:1346, 1994 : PubMed
An enzyme with acyl coenzyme A:cholesterol acyltransferase (ACAT) activity was isolated from porcine liver, and sequences derived from trypsinized peptides indicated homology to liver carboxylesterase. By use of degenerate primers, human cDNA clones were identified, which were identical to human liver carboxylesterase. Expression of the full-length cDNA in Chinese hamster ovary (CHO) cells led to an approximately threefold increase in cellular ACAT activity. This was accompanied by an approximately 20-fold increase of cellular cholesteryl ester content. By light and electron microscopy, recombinant CHO cells contained numerous lipid droplets that were not present in control CHO cells. Expression of an antisense cDNA in HepG2 cells reduced cellular ACAT activity by 35% compared with control. To further investigate the role of the enzyme in cellular cholesterol homeostasis, regulation of the mRNA was investigated in 7-day cultured human mononuclear phagocytes (MNPs). When these cells were incubated in lipoprotein-deficient serum for 18 hours, the mRNA for ACAT/carboxylesterase was almost not detectable on Northern blots, whereas after incubation with acetylated low-density lipoproteins, a strong hybridization signal was obtained. This is evidence that the mRNA of ACAT/carboxylesterase is induced by cholesterol loading. It is concluded from the data presented that ACAT/carboxylesterase is relevant for cellular cholesterol esterification in vivo. The regulation in MNPs indicates that the enzyme is also involved in foam cell formation during early atherogenesis.
A cDNA encoding human liver carboxylesterase and its gene were isolated. Nucleotide sequence analyses of the cDNA revealed that the predicted enzyme protein consists of 567 amino acids, including 18 amino acids of a putative signal peptide. Comparison of the deduced amino acid sequences of this enzyme with those of seven other carboxylesterases in various mammalian species, together with experimental data from several other laboratories, showed that these enzymes can be classified into three groups depending on the sequences at their carboxyl terminals and the presence or absence of one exon. A human carboxylesterase gene was found to span approximately 30 kb and to have 14 small exons. Alignments of this gene with those of human cholinesterase and rat cholesterol esterase indicated insertional sites at some introns and homologous amino acid sequences around them, although these genes have different numbers of exons. Thus the results supported the conclusion that these esterases evolved from a common ancestral gene.
Deficiency of the monocyte ectoenzyme non-specific esterase is described in a heredofamilial pattern in four patients with rheumatoid arthritis. No association with HLA status or rheumatoid factor seropositivity was found.
Title: Assignment of human monocyte/macrophage serine esterase 1 (HMSE1) to human chromosome 16q13-q22.1 and of its homologue to the proximal esterase cluster on mouse chromosome 8. (Abstract) Becker-Follmann J, Zschunke F, Parwaresch MR, Radzun HJ, Scherer G Ref: Cytogenet Cell Genet, 58:1997, 1991 : PubMed
A human liver carboxylesterase (CE)-encoding cDNA has been cloned using synthetic oligodeoxyribonucleotides (oligos) based on the known amino acid (aa) sequences of rabbit and rat liver CEs. The oligos hybridize specifically to DNA encoding liver CEs. The longest cDNA obtained from screening several cDNA libraries encodes about 80% of the protein and translates into an aa sequence which has a high degree of similarity with the sequences of liver CEs from other species. On hybridization to mRNA isolated from human liver, the cDNA gave a single band of about 2.0 kb consistent with its encoding a protein of less than 68 kDa. DNA obtained from a number of human livers and probed with the CE cDNA gave identical hybridization patterns. These patterns were moderately complex by comparison with published data.
Title: Purification and characterization of two human liver carboxylesterases Ketterman AJ, Bowles MR, Pond SM Ref: International Journal of Biochemistry, 21:1303, 1989 : PubMed
1. Two carboxylesterases (EC 3.1.1.1) purified from human livers were distinguished by pI (isoelectric point), nondenaturing polyacrylamide gel electrophoresis, molecular weight, catalytic activity, N-terminus and immunological cross-reactivity. 2. The low pI carboxylesterase has not been reported previously. 3. Numerous bands seen when each enzyme was focused on analytical IEF gels could not be separated. 4. When sections of the band pattern was refocused, the original complete band pattern was generated. 5. Both the mid and low pI carboxylesterases had catalytic activity for xenobiotics as well as medium and long chain fatty acid esters.
Monocyte esterase activity was studied in 1,000 doctor-attending patients with normal hematological indices and in 56 patients with non-Hodgkin's lymphoma (NHL) or B chronic lymphocytic leukemia (CLL). The incidence of esterase deficiency was significantly greater in the NHL-CLL patients (7.1%) than in the population group (1.7%; p less than 0.05). In the NHL-CLL group, study of the families showed the esterase deficiency to be a familial characteristic. We postulate that the presence of the anomaly may be either a factor predisposing to the development of the NHL or CLL or a factor indicating a predisposition to these disorders.
An inherited cytochemical staining abnormality of monocytes is described, affecting members of three generations of one family. alpha-Naphthyl acetate and alpha-naphthyl butyrate esterase staining reactions have been consistently negative in 95% of the monocytes of the propositus and her son and in 60-70% of the monocytes in two of four grandchildren.
