Postnatal hematologic development in phosphofructokinase-deficient dogs.
Adult dogs with phosphofructokinase (PFK) deficiency have compensated hemolytic anemia, due to an absolute or functional deficiency of the muscle-type (M-type) subunit that normally accounts for a majority of total erythrocyte PFK activity in dogs. Potential effects of PFK deficiency on hematologic development were evaluated in dogs. Routine hematologic parameters were similar in normal and affected dogs when 1 day old, because all newborn dogs had erythrocyte PFK activities about three times that of normal adult dogs. Based on chromatographic separation of PFK isozymes and enzyme immunoprecipitation studies, the high PFK activity at birth was attributed to the predominance of the liver-type (L-type) subunit of PFK, which is negligible or absent in normal adult dog erythrocytes. Both total PFK activities and the amounts of L-type subunit present decreased dramatically during the first 6 to 8 weeks of life. The muscle-type subunit was negligible or absent at birth, but appeared and increased as the L-type decreased in normal dogs. These changes may result from the replacement of erythrocytes formed in the fetus with those formed after birth. A postnatal physiologic anemia developed to a similar degree in both affected and normal dogs because of decreases in both mean corpuscular volume and erythrocyte numbers. Reticulocyte counts were high in all dogs at birth and remained high in affected dogs, but decreased from 2 months of age onward in normal dogs. Erythrocyte 2,3-diphosphoglycerate (DPG) values were very low in all newborn pups and increased to values expected for adults in the respective groups by 2 to 4 weeks of age. A low 2,3-DPG concentration occurs in affected dogs because PFK deficiency inhibits glycolysis above the side shunt that forms 2,3-DPG.
Harvey
J W
JW
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610.
Reddy
G R
GR
D000255:Adenosine Triphosphate / Q000097:blood; D000367:Age Factors; D000743:Anemia, Hemolytic / Q000201:enzymology / Q000662:veterinary*; D000818:Animals; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D004285:Dogs; D004906:Erythrocyte Count; D007527:Isoenzymes / Q000378:metabolism; D010375:Pedigree; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000235:genetics; D011770:Pyruvate Kinase / Q000097:blood; D012156:Reticulocytes
D007527:Isoenzymes; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase