Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of the key glycolytic enzymes phosphofructokinase (PFK), pyruvate kinase (PK) and hexokinase in addition to adenosine deaminase, purine nucleoside phosphorylase (PNP) and lactate dehydrogenase (LDH) have been measured in lymphocytes from 39 cases with B-chronic lymphocytic leukaemia (B-CLL). According to the percentage of circulating large non-granular atypical lymphocytes (AL) the B-CLL cases were classified as: typical (less than 10% of AL; 28 cases) and atypical (10-25% AL; 11 cases). In both groups the median lymphocyte volume (MLV) was assessed and correlated with the correspondent enzyme activities. The MLV of B-CLL lymphocytes was significantly (p less than 0.001) decreased (149.9 +/- 19.4 fl) as compared to normal B lymphocytes (175.1 +/- 14.5 fl) and it was significantly (p less than 0.001) lower in typical B-CLL (141.8 +/- 12.2 fl) than in atypical B-CLL (172.0 +/- 17.2 fl). Furthermore, in patients with typical B-CLL, all enzyme activities when expressed as U/10(9) cells were, with the exception of PFK, significantly decreased compared to normal B lymphocytes. However, when the results were expressed as U/ml cells, only PK, PNP and LDH remained significantly low. These findings demonstrate that the determination of MLV in addition to morphology may be a useful tool to distinguish the two previously described morphological B-CLL variants (typical and atypical) and that these two different B-CLL groups are also distinguishable on the basis of three enzyme activities, PK, PNP and LDH which have been shown to be less dependent on cell size than the other enzymes, also studied here.
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PMID:Relationship between lymphocyte size and enzyme activities in two morphological variants of B-chronic lymphocytic leukaemia. 252 63

The levels of activity of three enzymes have been measured in the circulating malignant lymphocytes of 47 patients with B chronic lymphocytic leukemia (CLL). These were the purine degradative enzymes, adenosine deaminase (ADA) and ecto-5'-nucleotidase (5'NT) and the enzyme responsible for the polyadenylation of mRNA, poly(A) polymerase. The patterns of activity of the above enzymes and the expression of surface immunoglobulin light chains were examined. A heterogeneity in the specific activity of the enzymes was observed which could not be attributed to variations of the percentage of B lymphocytes. A positive correlation was found between ADA and poly(A)polymerase activity (r = 0.383, p less than 0.01). Furthermore, the expression of immunoglobulin light chain phenotype was inversely related to 5'NT specific activity; CLL cases in which less than 20% of the cells expressed lambda chain phenotype, presented 5'NT specific activity of 16.7 +/- 3.3 (S.E.) nmol/h/10(6) cells, whereas in CLL cases with more than 20% of the cells expressing this phenotype the enzyme specific activity was 4.8 +/- 1.6 (S.E.) nmol/h/10(6) cells (p less than 0.02). These findings suggest that the simultaneous determination of enzymatic activities and immunological markers, might be useful in defining subsets in CLL and the subsequent clinical treatment.
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PMID:Patterns of adenosine deaminase, ecto-5'-nucleotidase, poly(A)polymerase and surface light chain expression in chronic lymphocytic leukemias. 253 69

Agents that cause the accumulation of DNA strand breaks are directly cytotoxic to non-dividing normal human peripheral blood lymphocytes, and to chronic lymphocytic leukemia (CLL) cells. Activation of poly(ADP-ribose) polymerase (ADPRP), and the resultant consumption of NAD, play an essential role in mediating the toxicity of these agents. Human peripheral blood lymphocytes contain a substantial number of alkali-sensitive DNA sites, reflecting ongoing DNA strand breakage and repair. However, resting lymphocytes have a limited capacity to synthesize NAD. Pulse-chase experiments indicate that approximately 75% of their NAD turnover is due to ADPRP activity. Exposure of the cells in vitro to deoxyadenosine, or to 2-chlorodeoxyadenosine (CdA, an adenosine deaminase resistant deoxyadenosine congener), caused an increase in DNA strand breaks, rapid NAD consumption, ATP depletion and cell death. Supplementation of the medium with inhibitors of poly(ADP-ribose) polymerase blocks the fall in cellular NAD and ATP, and protects the lymphocytes from the toxicity of DNA damaging agents. Slowly dividing malignant lymphocytes from patients with CLL are also susceptible to lethal NAD depletion following DNA damage. 2-chlorodeoxyadenosine (CdA) induced massive DNA strand break formation in CLL cells in vitro and a fall in NAD and ATP pools. In an initial clinical trial, several CLL patients, and two patients with hairy cell leukemia, have responded to treatment with CdA, with minimal toxicity. Thus, the suicidal activation of ADPRP in response to DNA damage has been rationally exploited in the treatment of chronic lymphoid malignancies.
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PMID:Programmed cell death and adenine deoxynucleotide metabolism in human lymphocytes. 290 67

Activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) as well as their ratio in chronic lymphocytic leukemia (CLL) were found to be several times lower as compared with normal cells and to depend upon the duration and severity of leukemic process. Ratio of ADA and PNP activities in CLL was inverted as compared with those of normal cells; 5'-nucleotidase activity varied within all the stages of the disease from zero values to supernormals. There was a correlation between beneficial effects of treatment of the CLL patients and an increase in ADA and PNP activities in their peripheral lymphocytes.
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PMID:[Enzymes of purine nucleotide catabolism in lymphocytes in normal states and in chronic lymphoid leukemia]. 299 63

Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.
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PMID:Low-dose deoxycoformycin in lymphoid malignancy. 299 34

Investigations of the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and ecto-5'-nucleotidase (5'NT) have been shown to be of value in defining subsets of lymphoid malignancies. We have studied the activities of these enzymes in the circulating malignant cells of 35 patients with chronic B lymphocytic leukaemia and have correlated the biochemical data with immunological phenotypes. Classification of the cases into those without evidence of secretory activity ('true' CLL, 14 patients) and those with cytoplasmic immunoglobulin (CIg) ('immunocytoma'; 21 patients) revealed that immunocytomas are phenotypically and biochemically associated with more mature features. Malignant cells without CIg were characterized by low activities of ADA, PNP and 5'NT. In malignant cells with evidence of secretory activity (immunocytoma), low activity of ADA was also observed, but the activities of PNP and 5'NT were relatively high and approached the range of normal B lymphocytes. The differences in PNP (P less than 0.05) and in 5'NT (P less than 0.01) between these two groups were significant. Phenotypically the cells without CIg were predominantly associated with IgM (+k light chains) as surface membrane immunoglobulin (SmIg) whereas expression of IgG was more often observed in the leukaemic cells with CIg. No correlation between enzyme patterns and the stage of the disease was apparent. Thus both biochemical and immunological criteria show that cases of CLL vary within a range of maturity and that those with CIg might be more mature in the B cell axis. The present study emphasizes the value of purine enzyme studies in defining subsets of B cell neoplasia.
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PMID:Purine degradative enzymes and immunological phenotypes in chronic B-lymphocytic leukaemia: indications that leukaemic immunocytoma is a separate entity. 300 40

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.
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PMID:Enzymes of purine metabolism in hairy cell leukemia. 301 Dec 39

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T-cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B-chronic lymphatic leukemia (B-CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with 'common' acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B-CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.
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PMID:Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia. 303 62

Promising results in the treatment of indolent lymphomas have been reported with the use of 2'deoxycoformycin. This antimetabolite, an adenosine deaminase inhibitor, also shows particular efficacy in hairy cell leukemia. Of 65 patients treated to date, 44 have achieved complete and lasting remission after a limited course of deoxycoformycin. While results are not as striking as those in hairy cell leukemia, deoxycoformycin may also be a valuable adjunct to alkylating agents in the treatment of CLL. The drug also is being studied in the treatment of mycosis fungoides and other lymphoid neoplasms. Side effects in all neoplasms are dose- and schedule-dependent.
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PMID:Deoxycoformycin: an active new drug for indolent lymphomas and hairy cell leukemia. 307 30

The levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), lactic dehydrogenase (LDH), and LDH isoenzyme patterns (LD1 to LD5) have been measured in lymphocyte extract from 28 patients with B-chronic lymphocytic leukemia (B-CLL). The activities of ADA, PNP, and LDH have been correlated with two morphological groups of B-CLL classified according to the percentage of large, nongranular, atypical lymphocytes (AL) in peripheral blood: "typical" B-CLL (less than 10% of AL, 21 cases) and "atypical" B-CLL (10-25% of AL, seven cases). Patients with atypical B-CLL had significantly (P less than 0.001) higher activities of ADA (0.46 +/- 0.17 U/10(9) cells), PNP (1.74 +/- 1.0 U/10(9) cells), and LDH (48.3 +/- 9.7 U/10(9) cells) than patients with typical B-CLL (ADA, 0.29 +/- 0.1 U/10(9) cells; PNP, 0.58 +/- 0.23 U/10(9) cells; and LDH, 29 +/- 10 U/10(9) cells). In addition, the "treatment-free period" was also significantly (P less than 0.025) shorter in the group of atypical B-CLL compared with the typical B-CLL group. No clear-cut statistical differences in lymphocyte surface markers or in several other prognostic factors between the two subgroups of B-CLL were found. The present study supports the idea that in B-CLL the simultaneous determination of ADA, PNP, and LDH might be helpful in better understanding the pathophysiology, prognosis, and natural history of the disease.
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PMID:Combined assay of adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in the early clinical evaluation of B-chronic lymphocytic leukemia. 312 50


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