Hemopexin, The Heme-Binding Serum β-Glycoprotein

Müller‐Eberhard, Ursula; Liem, H. H.

doi:10.1007/978-1-4684-2676-2_2

Cited by 29 publications

(20 citation statements)

References 62 publications

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“…While it may be that hemopexin binds PP somewhat more strongly than does albumin, the large ratio of concentrations of albumin to hemopexin, approximately 100:1 in all species examined (30) served for erythrocytes obtained from both EPP patients and GFPP mice. That the hemoglobin-PP and stroma-PP are in equilibrium in vivo is demonstrated by the invariance of their ratio for EPP erythrocytes of different age, of which the average total PP content varied by a factor of four (Table III).…”

Section: Methodsmentioning

confidence: 96%

Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-Induced Murine Protoporphyria

Poh–Fitzpatrick¹,

Lamola²,

Zalar³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Excess erythrocyte protoporphyrins of human congenital erythropoietic protoporphyria and of griseofulvin-induced murine hepatic protoporphyria were found to be associated with hemoglobin and stroma fractions in similar relationships. More than 99.5% of total erythrocyte protoporphyrin was bound to hemoglobin in each case. However, profound differences were found when protoporphyrin concentration was measured in erythrocytes that had been segregated into populations of progressive age on discontinuous density gradients. In erythropoietic protoporphyria, porphyrin content diminished rapidly with age; in murine protoporphyria, the aging erythrocyte populations became progressively more porphyrin rich. In vitro diffusion of protoporphyrin from plasma across the intact erythrocyte membrane was demonstrated. The equimolar binding affinity of protoporphyrin to hemoglobin was shown to be 40 times that of protoporphyrin to serum albumin. This strong affinity provides the driving force for the observed transmembrane diffusion, and explains the high erythrocyte/plasma porphyrin ratio in murine hepatic protoporphyria. The opposite rapid efflux of intraerythrocytic protoporphyrin into plasma previously shown in uncomplicated erythropoietic protoporphyria occurs despite this strong hemoglobin affinity, implying continuous efficient clearance of protoporphyrin from plasma by the liver. Furthermore, these and other This work was presented in part at the 7th International Congress on Photobiology, Rome, Italy, September, 1976. Received for publication 22 November 1976 and in revised form 29 March 1977. data suggest that a hepatic synthetic source for any significant fraction of the blood protoporphyrin in erythropoietic protoporphyria is highly improbable. INTRODUCTION Congenital protoporphyria in humans was first named erythropoietic protoporphyria (EPP)' (1-3) based upon the large amounts of protoporphyrin IX (PP) found in the blood of patients with the disease which was thought to be synthesized in the bone marrow. However, the observation was made that the daily excretion of PP in the feces of these patients approached the total excess PP in the circulating erythrocyte mass. It was clear that this amount could not be derived from senescent erythrocytes only (4). Some investigators proposed the liver as an important additional source of PP in this disease. Acquired protoporphyria is extremely rare in man, but protoporphyria can be easily induced in mice with certain drugs, among which is griseofulvin (GF) (9-11). Murine protoporphyria induced by oral administration of GF has been used as an experimental model for human EPP (12,13). The site of excess PP synthesis in GF-induced murine protoporphyria (GFPP) is thought to be primarily, if not solely, hepatic (14). However, the concentration of PP associated with the circulating erythrocytes in GFPP can become comparable to that observed in EPP (9, 13, 14).We have developed spectrofluorometric techniques which give information about the binding sites of PP ...

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Section: Methodsmentioning

confidence: 96%

Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-Induced Murine Protoporphyria

Poh–Fitzpatrick¹,

Lamola²,

Zalar³

et al. 1977

J. Clin. Invest.

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“…Little is known about the conformation of hemopexin or the heme-binding site (1). Therefore, we used the computer program PRPLOT (14) to predict and plot the local secondary structure of the polypeptide chain by the empirical method of Chou and Fasman (17), the parameters for which are based mainly on proteins that lack oligosaccharides.…”

Section: T P L P P T S a Hmn V A E G Etk P Dpd V T Ersd G W S F Datt mentioning

confidence: 99%

“…Hemopexin, the serum (3-glycoprotein that binds one heme with high affinity, has been widely studied because of its physiological role in heme transport and catabolism and its decrease in hemolytic diseases (1)(2)(3). Although the protein was purified (4) and characterized by physical and chemical methods (5-7) soon after its discovery in 1958 (8), nothing except a partial amino-terminal sequence (9) was published about the structure of hemopexin until our recent reports on the O-glycosyl and N-glycosyl sites and the unusual clustering of tryptophan residues (10,11).…”

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confidence: 99%

Complete amino acid sequence of human hemopexin, the heme-binding protein of serum.

Takahashi¹,

Takahashi²,

Putnam³

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…Hemopexin has a higher binding affinity for metalloporphyrins than albumin (15) and is instrumental in the disposal of heme (5,8,9,14,19). The liver is the site of hemopexin synthesis in rhesus monkeys (17), rabbits (17), and rats (12).…”

Section: Speculationmentioning

confidence: 99%

Hemopexin Synthesis in Vitro by Human Fetal Tissues

et al. 1975

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ExtractSerum concentrations of hemopexin, transferrin, and albumin were measured for 12 fetuses between 14 and 36 weeks of gestational age. Hemopexin levels ranged from 7 to 64 pg/ml, transferrin levels ranged from 280 to 928 pg/ml, and albumin levels ranged from 13 to 59 mg/ml. In general, the serum concentrations of these three proteins increased with advancing gestation.Placenta, thymus, and colon did not incorporate 14C-labeled amino acids into hemopexin, transferrin, or albumin. By contrast, radioimmune precipitates for five culture supernatants of liver indicated significant synthesis of albumin and hemopexin.[MC]Albumin accounted for 22-73% and [14C]hemopexin 1.1-4.2% of the total 14C-labeled proteins. In each instance, the ["Cltransferrin was below 1% of the total l 4 C-labeled proteins. SpeculationThese data show considerable synthesis of albumin and hemopexin, but not transferrin, by the liver during fetal life. That hemopexin levels are lower in fetal than adult sera may reflect an increased requirement for heme disposal. Possibly, the increased turnover of hemopexin is related to the shortened lifespan of fetal in comparison with adult erythrocytes.Mammalian serum contains two major porphyrin-binding proteins, hemopexin and albumin (1 I). Hemopexin has a higher binding affinity for metalloporphyrins than albumin (15) and is instrumental in the disposal of heme (5,8,9,14,19). The liver is the site of hemopexin synthesis in rhesus monkeys (17), rabbits (17), and rats (12). In the present study, human fetal tissues were cultured and examined for the relative amounts of hemopexin, albumin, and transferrin produced. MATERIALS A N D METHODS FETAL TISSUESSerum samples of fetuses were obtained by heart puncture.Tissuc culturcs of livcr, placenta, thymus, a n d colon of h u m a n fetuses, 12-25 weeks old, were developed by Dr. Peter F. Kohler (20), employing [14C]lysine and [14C]isoleucine (4). Culture supernatants were dialyzed against 0.015 M phosphate-buffered saline (PBS), pH 7.4, lyophilized, dissolved in distilled water (0.2-0.3 ml), shipped to La Jolla on Dry Ice, and stored at 7 0°.Tissues for absorption of antisera were obtained from fetuses within 5 hr of saline-induced abortion. Small pieces of liver, placenta, thymus, and colon were passed through a stainless steel mesh with the aid of screen rakes. Cells were washed three times with PBS and mixed with 3 volumes antiserum/l volume of cells. The mixtures were incubated at 37O for 30 min, at 4' for 48 hr, and then the cells were removed by centrifugation at 1,200 x g for 30 min. T o 5-50-pl aliquots of culture supernatant, 50 1 1 normal human serum as carrier protein were added and the nonspecific radioactivity was precipitated by addition of equivalent amounts of R G G and anti-BGG. T h e mixture was incubated 37' for 30 min, at 4' overnight, and centrifuged at 1,200 x g for 30 min at 4'. The supernatants were then used for precipitation with the monospecific antisera added to antibody excess. The reaction mixtures were incubated and centrifuged as...

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Hemopexin, The Heme-Binding Serum β-Glycoprotein

Cited by 29 publications

References 62 publications

Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-Induced Murine Protoporphyria

Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-Induced Murine Protoporphyria

Complete amino acid sequence of human hemopexin, the heme-binding protein of serum.

Hemopexin Synthesis in Vitro by Human Fetal Tissues

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