Hereditary erythrocyte adenylate kinase deficiency: a defect of multiple phosphotransferases?
Adenylate kinase (AK) modulates the interconversion of adenine nucleotides (AMP + adenosine triphosphate----2 ADP). We evaluated the fifth kindred with hereditary erythrocyte (RBC) AK deficiency. The proband had chronic hemolytic anemia. Her RBC had undetectable AK activity when measured spectrophotometrically, whereas those of her parents had half-normal AK activity. AK electrophoresis showed only AK-1 in the parents. The activities of pyruvate kinase and phosphoribosylpyrophosphate synthetase were decreased given the young age of the proband's RBC. Despite the absence of spectrophotometric AK activity, the proband's RBC were able to incorporate 14C-adenine into 14C-adenine nucleotides at 50% of the rate expected for her young RBC population, suggesting the possibility of an alternative pathway for the formation of ADP from AMP. Normal hemolysate had AMP:guanosine triphosphate (GTP) phosphotransferase activity, which produced ADP at 8% to 9% of the rate of AK (6.8 +/- 0.8 IU/mL RBC). AMP:GTP phosphotransferase activity was not detectable in the proband's or parent's hemolysates. These additional biochemical defects in the AK-deficient RBC further support the concept that AK deficiency per se may not cause hemolytic anemia. We propose that defects occur in multiple phosphotransferases in the AK-deficient RBC and that these other biochemical defects may produce deleterious lesions that promote the shortened RBC survival in AK deficiency.
Lachant
N A
NA
Department of Medicine, Harbor UCLA Medical Center, UCLA School of Medicine, Torrance.
Zerez
C R
CR
Barredo
J
J
Lee
D W
DW
Savely
S M
SM
Tanaka
K R
KR
D000244:Adenosine Diphosphate / Q000097:blood; D000249:Adenosine Monophosphate / Q000097:blood; D000255:Adenosine Triphosphate / Q000097:blood; D000263:Adenylate Kinase / Q000097:blood / Q000172:deficiency*; D000743:Anemia, Hemolytic / Q000201:enzymology* / Q000235:genetics; D002675:Child, Preschool; D004588:Electrophoresis, Cellulose Acetate; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005978:Glutathione / Q000097:blood; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009703:Nucleoside-Phosphate Kinase; D010770:Phosphotransferases / Q000097:blood*; D011189:Potassium Chloride / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D013439:Sulfhydryl Reagents; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D006427:Hemin; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C021894:nucleoside triphosphate-adenylate kinase; D000263:Adenylate Kinase; D009703:Nucleoside-Phosphate Kinase; D005978:Glutathione; D008274:Magnesium