Original article| Volume 102, ISSUE 5, P838-846, November 1983

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Hemopexin metabolism in patients with altered serum levels

  • M. Foidart
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  • H.H. Liem
    From the Departments of Pediatrics and Pharmacology, The New York Hospital-Cornell Medical Center, New York, N. Y., USA
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  • B.T. Adornato
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  • W.K. Engel
    From the Medical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Md., USA
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  • U. Muller-Eberhard
    Reprint requests: Ursula Muller-Eberhard, Departments of Pediatrics and Pharmacology, N-804, The New York Hospital-Cornell Medical Center, 525 East 68th St., New York, N. Y. 10021.
    From the Medical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Md., USA
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  • Author Footnotes
    1 Present address: Department of Physiotherapy, University of Liège, Liège, Belgium.
    3 Present address: Palo Alto Medical Clinic and Research Foundation, 300 Homer Ave., Palo Alto, Calif. 94301.
    4 Present address: USC Neuromuscular Center, Department of Neurology, Hospital of the Good Samaritan, 637 South Lucas, Los Angeles, Calif. 90017.
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      The rates of synthesis and degradation of hemopexin (Hx) were studied in vivo to determine the cause of altered serum levels of this protein as seen in hemolytic anemias, chronic neuromuscular diseases, and acute intermittent porphyria. The synthetic and fractional catabolic rates of Hx were measured in patients exhibiting low, normal, or elevated serum Hx levels. It was found that the elevated levels were mainly due to increased synthesis rather than decreased catabolism of Hx. In patients with elevated serum Hx levels, the mean synthetic rate of Hx (13 ± 1.0 mg/kg/day) was twice that of the patients with normal Hx levels (6.6 ± 0.3), whereas the fractional catabolic rate was 35.3 ± 7.1% of the i.v. pool per day vs. 26.5 ± 0.8 for controls. The low serum Hx levels observed in patients with sickle cell anemia appeared to be due to increased Hx catabolism (36.0 and 40.0% of the i.v. pool per day vs. 26.5 ± 0.8 for controls) with no compensatory increase in synthesis. This latter finding is in agreement with a study in rhesus monkeys in which repeated administration of a large dose of heme caused an increase in the catabolism of hemopexin without a concurrent increase in its synthesis (J Lab Clin Med 100:451, 1982). Our results indicate that although both synthesis and catabolism are increased in patients with elevated Hx levels, only catabolism is increased in patients with sickle cell anemia.


      (heme) (iron protoporphyrin IX regardless of oxidation state), (Hx) (hemopexin), (AIP) (acute intermittent porphyria), (DMD) (Duchenne muscular dystrophy), (SCA) (sickle cell anemia), (NP) (idiopathic sensory neuropathy), (ALS) (amyotrophic lateral sclerosis), (NSM) (morphologically nonspecific myopathy), (MG) (myasthenia gravis), (PM) (polymyositis), (TCA) (trichloroacetic acid), (CPK) (creatinine phosphokinase), (t12) (half-life)
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        • Heide K
        • Haupt H
        • Stoeriko K
        • Schultze HE
        On the heme-binding capacity of hemopexin.
        Clin Chim Acta. 1964; 10: 460
        • Muller-Eberhard U
        • Morgan WT
        Porphyrin-binding proteins in serum.
        Ann NY Acad Sci. 1975; 244: 624
        • Muller-Eberhard U
        Heme transport and properties of hemopexin.
        in: Blauer G Sund H Transport by Proteins. Walter de Gruyter & Co, Berlin1978: 295
        • Morgan WT
        • Muller-Eberhard U
        Interactions of porphyrins with rabbit hemopexin.
        J Biol Chem. 1972; 247: 7181
        • Morgan WT
        • Sutor RP
        • Muller-Eberhard U
        • Koskelo P
        Interaction of rabbit hemopexin with copro- and uroporphyrins.
        Biochim Biophys Acta. 1975; 400: 415
        • Seery VL
        • Muller-Eberhard U
        Binding of porphyrins to rabbit hemopexin and albumin.
        J Biol Chem. 1973; 248: 3796
        • Morgan WT
        • Smith A
        • Koskelo P
        The interaction of human serum albumin and hemopexin with porphyrins.
        Biochim Biophys Acta. 1980; 624: 271
        • Lamola AA
        • Asher I
        • Muller-Eberhard U
        • Poh-Fitzpatrick M
        Fluorimetric study of the binding of protoporphyrin to haemopexin and albumin.
        Biochem J. 1981; 196: 693
        • Muller-Eberhard U
        • Bosman C
        • Liem HH
        Tissue localization of the heme-hemopexin complex in the rabbit and the rat as studied by light microscopy with the use of radioisotopes.
        J Lab Clin Med. 1970; 76: 426
        • Liem HH
        Hepatic uptake of heme and hemopexin but not albumin.
        Biochim Biophys Acta. 1974; 343: 546
        • Smith A
        • Morgan WT
        Haem transport to the liver by haemopexin. Receptor-mediated uptake with recycling of the protein.
        Biochem J. 1979; 182: 47
        • Koskelo P
        • Muller-Eberhard U
        Interaction of porphyrins with proteins.
        in: Semin Hematology. 14. 1977: 221
        • Muller-Eberhard U
        • Javid J
        • Liem HH
        • Hanstein A
        • Hanna M
        Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases.
        Blood. 1968; 32: 811
        • Sears DA
        Disposal of plasma heme in normal man and patients with intravascular hemolysis.
        J Clin Invest. 1970; 49: 5
        • Adornato BT
        • Kagen LJ
        • Garver FA
        • Engel WK
        Depletion of serum hemopexin in fulminant rhabdomyolysis.
        Arch Neurol. 1978; 35: 547
        • Meyer UA
        • Schmid R
        Hereditary hepatic porphyrias.
        in: Fed Proc. 32. 1973: 1649
        • Watson CJ
        • Pierach CA
        • Bossenmaier I
        • Cardinal R
        Postulated deficiency of hepatic heme and repair by hematin infusions in the “inducible” hepatic porphyrias.
        in: Proc Natl Acad Sci USA. 74. 1977: 2118
        • Lamon JM
        • Tschudy DP
        • Muller-Eberhard U
        Hematin therapy in acute porphyria and observations on hemopexin.
        in: Doss M Diagnosis and Therapy of Porphyrias and Lead Intoxication. Springer Verlag, Berlin1978: 285
        • Askanas W
        • Mazurczak J
        The serum immunoelectrophoretic test in patients with Duchenne's progressive muscular dystrophy. Preliminary report.
        Life Sci. 1966; 5: 247
        • Askanas W
        Immunoelectrophoretic investigations of blood serum proteins in muscular diseases.
        J Neurol Neurosurg Psychiat. 1967; 30: 43
        • Danieli GA
        • Angelini C
        Duchenne carrier detection.
        Lancet. 1976; 2: 90
        • Adornato BT
        • Engel WK
        • Foidart-Desalle M
        Elevations of hemopexin levels in neuromuscular disease.
        Arch Neurol. 1978; 35: 577
        • Kagen LJ
        Myoglobinemia in inflammatory myopathies.
        JAMA. 1977; 237: 1448
        • Nishikai M
        • Reichlin M
        Radioimmunoassay of serum myoglobin in polymyositis and other conditions.
        Arthritis Rheum. 1977; 20: 1514
        • Adornato BT
        • Kagen LJ
        • Engel WK
        Myoglobinaemia in Duchenne muscular dystrophy patients and carriers: a new adjunct to carrier detection.
        Lancet. 1978; 2: 499
        • Wochner RD
        • Spilberg I
        • Iio A
        • Liem HH
        • Muller-Eberhard U
        Hemopexin metabolism in sickle-cell disease, porphyrias and control subjects. Effects of heme injection.
        N Engl J Med. 1974; 290: 822
        • Vretblad P
        • Hjorth R
        The use of wheat-germ lectin-Sepharose for the purification of human haemopexin.
        Biochem J. 1977; 167: 759
        • McConahey PJ
        • Dixon FJ
        A method of trace iodination of proteins for immunologic studies.
        Int Arch Allergy. 1966; 29: 185
        • Bolton AE
        • Hunter WM
        The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent.
        Biochem J. 1973; 133: 529
        • Mancini G
        • Carbonara AO
        • Heremans JF
        Immunochemical quantitation of antigens by single radial immunodiffusion.
        Immunochemistry. 1965; 2: 235
        • Zweig MH
        • Adornato B
        • Van Steirteghem AC
        • Engel WK
        Serum creatinine kinase: BB and MM concentrations determined by radioimmunoassay in neuromuscular disorders.
        Ann Neurol. 1980; 7: 324
        • Matthews CME
        The theory of tracer experiments with 131I-labelled plasma proteins.
        Phys Med Biol. 1957; 2: 36
        • Donato L
        • Matthews CME
        • Nosslin B
        • Segre G
        • Vitek F
        Applications of tracer theory to protein turnover studies.
        in: Conference on problems connected with the preparation and use of labeled proteins in tracer studies. J Nucl Biol Med. 10. 1966: 3
        • Thorbecke GJ
        • Liem HH
        • Knight S
        • Cox K
        • Muller-Eberhard U
        Sites of formation of the serum proteins transferrin and hemopexin.
        J Clin Invest. 1973; 52: 725
        • Muller-Eberhard U
        • Liem HH
        • Cox KH
        • Conway TP
        Hemopexin synthesis in vitro by human fetal tissues.
        Pediatr Res. 1975; 9: 519
        • Pearson JD
        • Veall N
        • Vetter H
        A practical method for plasma albumin turnover studies.
        Strahlentherapie [Sonderb]. 1958; 38: 290
        • Fisher ER
        • Silvestri E
        • Vester JW
        • Nolan S
        • Ahmad U
        • Danowski TS
        Increased erythrocytic osmotic fragility in pseudohypertrophic muscular dystrophy.
        JAMA. 1976; 236: 955
        • Adornato BT
        • Corash L
        • Engel WK
        Erythrocyte survival in Duchenne muscular dystrophy.
        Neurology. 1977; 27: 1093
        • Muller-Eberhard U
        • Grizzuti K
        Conformational studies on human and rabbit plasma hemopexin and on the effect of ligands on the rabbit heme-hemopexin complex.
        Biochemistry. 1971; 10: 2062
        • Morgan WT
        • Vickery LE
        Magnetic and natural circular dichroism of metalloporphyrin complexes of human and rabbit hemopexin.
        J Biol Chem. 1978; 253: 2940
        • Javid J
        • Fuhrman MH
        • Liem HH
        • Northway A
        • Muller-Eberhard U
        Immunologic differentiation of free and heme-bound rabbit hemopexin.
        J Lab Clin Med. 1972; 80: 817
        • Lane RS
        • Rangeley DM
        • Liem HH
        • Wormsley S
        • Muller-Eberhard U
        Plasma clearance of 125I-labelled haemopexin in normal and haem-loaded rabbits.
        Br J Haematol. 1973; 25: 533
        • Liem HH
        • Spector JI
        • Conway TP
        • Morgan WT
        • Muller-Eberhard U
        Effect of hemoglobin and hematin on plasma clearance of hemopexin, photoinactivated hemopexin and albumin.
        in: Proc Soc Exp Biol Med. 148. 1975: 519
        • Conway TP
        • Morgan WT
        • Liem HH
        • Muller-Eberhard U
        Catabolism of photooxidized and desialylated hemopexin in the rabbit.
        J Biol Chem. 1975; 250: 3067
        • Foidart M
        • Eiseman J
        • Engel WK
        • Adornato BT
        • Liem HH
        • Muller-Eberhard U
        Effect of heme administration on hemopexin metabolism in the rhesus monkey.
        J Lab Clin Med. 1982; 100: 451
        • Liem HH
        Catabolism of homologous and heterologous hemopexin in the rat and uptake of hemopexin by isolated perfused rat liver.
        Ann Clin Res. 1976; 8: 233
        • Muller-Eberhard U
        • Liem HH
        • Hanstein A
        • Saarinen PA
        Studies on the disposal of intravascular heme in the rabbit.
        J Lab Clin Med. 1969; 73: 210