Human spleen heme oxygenase in normal, hemolytic and other pathological states.
Heme oxygenase (HO), the primary enzyme responsible for heme catabolism, was measured in spleens from 10 normal subjects, 14 patients with chronic hemolytic anemia (HA), 12 with idiopathic thrombocytopenic purpura (ITP), and 10 with various lymphoproliferative disorders (LD) to determine the splenic enzymatic capacity for heme catabolism and the response of splenic HO to hemolysis. Splenic NADPH-cytochrome c reductase activity and cytochrome P-450 levels were also measured. Splenic HO specific activity in normal spleens was 0.235 +/- 0.106 (SE) nmoles bilirubin/mg protein/min; in HA, 0.276 +/- 0.050; in ITP, 0.228 +/- 0.036; and in LD, 0.420 +/- 0.105. However, the total HO activity per spleen was significantly greater in HA (742.9 +/- 137.4 (SE) nmoles/min, p less than 0.001) and LD (681.9 +/- 180.3, p less than 0.005) than in normal spleens (137.1 +/- 55.0), but was not significantly increased in ITP (269.5 +/- 121.5). In normal spleens cytochrome P-450 was 0.052 +/- 0.006 (SE) nmoles/mg and NADPH-cytochrome c reductase activity was 8.3 +/- 2.2 (SE) nmoles/mg/min; neither of these specific activities was significantly altered in HA, ITP, or LD. Again, total activity was significantly increased in HA and LD associated with increased splenic size. Although total HO activity is greater in the larger spleens, HO activity does not increase per unit weight of tissue. In normal spleen the calculated capacity for bilirubin production by HO was 115 mg per day. This accounts for only 50% of normal daily production from erythroid sources and suggests that other sites are of major importance for hemoglobin degradation.
D000743:Anemia, Hemolytic / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D009196:Myeloproliferative Disorders / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size; D010105:Oxygenases / Q000378:metabolism*; D011696:Purpura, Thrombocytopenic / Q000201:enzymology*; D013154:Spleen / Q000201:enzymology*
D006454:Hemoglobins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase