TY - JOUR
T1 - Schistosoma mansoni
T2 - Mechanisms in regulation of glycolysis
AU - Shapiro, Theresa A.
AU - Talalay, Paul
N1 - Funding Information:
These studiesw ere supportedb y U.S. National In-stituteso f Health Research Grants GM 16492a nd AI 18349,T raining Grant GM 1183,a nd United States Agency for International Development Contract D.P.E.-5921-G-00-1009-00T.h eresa A. Shapiro is a Fellow of the StetlerF oundation.T he helpful advice of our colleague Professor Ernest Bueding is acknowledged with gratitude. Miss Marguerite Renaud provided expert technical assistance. REFERENCES AMELUNXEN, R. E., AND CARR, D. 0. 1975. Glyc-eraldehyde-3-phosphated ehydrogenasef rom rab-bit muscle. In “Methods in Enzymology” (W. A. Wood, ed.), Vol. 41, pp. 264-267. Academic Press, New York. BOXER, G. E., AND SHONK, C. E. 1960.L ow levels of soluble DPN-linked-cY-glycerophosphated ehydro-genasei n tumors.C ancer Research 20, 85-91. BRAZIER, J. B., AND JAFFE, J. J. 1973.T wo types of pyruvate kinase in schistosomesa nd tilariae. Com-parative Biochemistry and Physiology 44B, 145-155. BRUCE, J. I., AND RADKE, M.G. 1971. Culturing Biomphalaria and Oncomalania (Gastropoda) for large-scales tudieso f schistosomiasisI.n “Biomedi-
PY - 1982/12
Y1 - 1982/12
N2 - Adult pairs of Schistosoma mansoni convert glucose to lactate rapidly and almost quantitatively under aerobic and anaerobic conditions E. Bueding, 1950, Journal of General Physiology 33, 475-495). Glycolysis is the principal source of energy of schistosomes and its inhibition by trivalent organic antimonials, at the phosphofructokinase step [EC 2.7.1.11], may be the basis for the chemotherapeutic effects of these agents E. Bueding and J. M. Mansour, 1957, British Journal of Pharmacology and Chemotherapy 12, 159-165). We have developed standardized conditions for the comparison of rates of glucose consumption and lactate production by intact schistosomes in vitro and by centrifuged homogenates of worms. The rates of glycolysis of homogenates prepared from freshly isolated worms, and from worms that have been lyophilized immediately after harvesting and stored for prolonged periods at -80 C were identical, when measured in media containing appropriate concentrations of glucose, NAD, ATP, MgCl2, KCl, and phosphate. The specific activities of the 11 glycolytic enzymes and of 3 related enzymes (fructose-biphosphatase [EC 3.1.3.11], glycerol-3-phosphate dehydrogenase [EC 1.1.1.8], and malate dehydrogenase [EC 1.1.1.37]) were measured in homogenates under optimal conditions. The profile of the relative activities of glycolytic enzymes of S. mansoni resembles closely that of Ehrlich ascites tumor cells, and differs markedly from that observed in erythrocytes or skeletal muscle. As is the case in many animal tissues, hexokinase [EC 2.7.1.1] was the enzyme of lowest specific activity, and the rate of glycolysis of homogenates was almost the same as the hexokinase activity. Several other lines of evidence support the view that the hexokinase reaction is the rate-limiting step in the glycolysis of worm homogenates. Hexokinase activity was not particulate in schistosome homogenates, and there was no detectable high Km glucokinase-like activity. The rate of glycolysis by homogenates exceeded that of intact worms by a factor of nearly 5. The contributions of glucose transport, availability of ADP and inorganic phosphate, regulatory enzymes, and a substrate cycle catalyzed by fructose-bisphosphatase are considered as possible mechanisms for the restraint of glycolysis in intact worms. The mechanisms contributing to the rapid rates of glycolysis of adult S. mansoni have not been identified, although several can be excluded (unusually high capacity of the glycolytic enzymes, the presence of mitochondrial hexokinase, the occurrence of glycosomes, and the operation of defective mitochondrial shuttles). In view of the regulatory role of hexokinase in the glycolysis of S. mansoni, inhibition of this enzyme is a potentially important target for the development of new antischistosomal drugs.
AB - Adult pairs of Schistosoma mansoni convert glucose to lactate rapidly and almost quantitatively under aerobic and anaerobic conditions E. Bueding, 1950, Journal of General Physiology 33, 475-495). Glycolysis is the principal source of energy of schistosomes and its inhibition by trivalent organic antimonials, at the phosphofructokinase step [EC 2.7.1.11], may be the basis for the chemotherapeutic effects of these agents E. Bueding and J. M. Mansour, 1957, British Journal of Pharmacology and Chemotherapy 12, 159-165). We have developed standardized conditions for the comparison of rates of glucose consumption and lactate production by intact schistosomes in vitro and by centrifuged homogenates of worms. The rates of glycolysis of homogenates prepared from freshly isolated worms, and from worms that have been lyophilized immediately after harvesting and stored for prolonged periods at -80 C were identical, when measured in media containing appropriate concentrations of glucose, NAD, ATP, MgCl2, KCl, and phosphate. The specific activities of the 11 glycolytic enzymes and of 3 related enzymes (fructose-biphosphatase [EC 3.1.3.11], glycerol-3-phosphate dehydrogenase [EC 1.1.1.8], and malate dehydrogenase [EC 1.1.1.37]) were measured in homogenates under optimal conditions. The profile of the relative activities of glycolytic enzymes of S. mansoni resembles closely that of Ehrlich ascites tumor cells, and differs markedly from that observed in erythrocytes or skeletal muscle. As is the case in many animal tissues, hexokinase [EC 2.7.1.1] was the enzyme of lowest specific activity, and the rate of glycolysis of homogenates was almost the same as the hexokinase activity. Several other lines of evidence support the view that the hexokinase reaction is the rate-limiting step in the glycolysis of worm homogenates. Hexokinase activity was not particulate in schistosome homogenates, and there was no detectable high Km glucokinase-like activity. The rate of glycolysis by homogenates exceeded that of intact worms by a factor of nearly 5. The contributions of glucose transport, availability of ADP and inorganic phosphate, regulatory enzymes, and a substrate cycle catalyzed by fructose-bisphosphatase are considered as possible mechanisms for the restraint of glycolysis in intact worms. The mechanisms contributing to the rapid rates of glycolysis of adult S. mansoni have not been identified, although several can be excluded (unusually high capacity of the glycolytic enzymes, the presence of mitochondrial hexokinase, the occurrence of glycosomes, and the operation of defective mitochondrial shuttles). In view of the regulatory role of hexokinase in the glycolysis of S. mansoni, inhibition of this enzyme is a potentially important target for the development of new antischistosomal drugs.
KW - Aldolase [EC 4.1.2.13]
KW - Blood fluke
KW - Enolase [EC 4.2.1.11]
KW - Fructose-bisphosphatase [EC 3.1.3.11]
KW - Glucosephosphate isomerase [EC 5.3.1.9]
KW - Glyceraldehyde-phosphate dehydrogenase [EC 1.2.1.12]
KW - Glycerol-3-phosphate dehydrogenase [EC 1.1.1.8]
KW - Glycolysis
KW - Hexokinase [EC 2.7.1.1]
KW - Lactate dehydrogenase [EC 1.1.1.27]
KW - Malate dehydrogenase [EC 1.1.1.37]
KW - Phosphofructokinase [EC 2.7.1.11]
KW - Phosphoglycerate kinase [EC 2.7.2.3]
KW - Phosphoglyceromutase [EC 2.7.5.3]
KW - Pyruvate kinase [EC 2.7.1.40]
KW - Regulation
KW - Schistosoma mansoni
KW - Trematode
KW - Triosephosphate isomerase [EC 5.3.1.1]
KW - adult
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U2 - 10.1016/0014-4894(82)90047-9
DO - 10.1016/0014-4894(82)90047-9
M3 - Article
C2 - 7151946
AN - SCOPUS:0020356753
VL - 54
SP - 379
EP - 390
JO - Experimental Parasitology
JF - Experimental Parasitology
SN - 0014-4894
IS - 3
ER -