فایل ورد کامل هاپتوگلوبین سرم خونی در زیست شیمی بالینی: تغییر یک نمونه

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تعداد صفحات این فایل: ۹ صفحه

بخشی از مقاله انگلیسیعنوان انگلیسی:Serum haptoglobin in clinical biochemistry: Change of a paradigm~~en~~

Abstract

Serum haptoglobin (Hp) was discovered by Max Fernand Jayle as a young assistant professor in the Department of Biochemistry of the Paris Medical Faculty, headed by Professor Michel Polonovski. Jayle showed that Hp was an acute phase glycoprotein and worked out its routine determination in the blood-serum, based on its complex formation with hemoglobin, using the increased peroxidase activity of the hemoglobin–haptoglobin (Hb–Hp) complex, for routine determination in clinical biochemistry for the characterisation of inflammatory processes, together with other acute phase glycoproteins as orosomucoide. Later Smithies described the genetic control of human Hp-isoforms and quite recently Andersen et al. reported the elucidation of the crystal structure of the porcine Hb–Hp complex. In that article there was no mention of the discovery of Hp, neither of its determination in clinical biochemistry as an inflammatory marker. The only biologically significant role assigned to Hp by Andersen et al. is its (hypothetical) role to prevent or minimize the harmful effects of Hb during intravascular hemolysis, by the generation of reactive oxygen species (ROS) and complexing it. This shift of paradigm, not at all exceptional in medical biochemistry, will be described and discussed with its pitfalls and consequences.

۲ Introduction

The recent publication by an international team of the detailed three-dimensional structure of the porcine hemoglobin–haptoglobin (Hb–Hp) complex [1] reminded me decades of research in the Department of Biochemistry of the Paris Medical Faculty, under the direction of the discoverers of haptoglobin, M. Polonovski and M.F. Jayle. The routine use of Hp determination as an acute phase glycoprotein, together with some other inflammatory markers such as orosomucoid or alpha1-acid glycoprotein [2,3] was practiced for decades in clinical biochemistry laboratories. As every innovation in medical biochemistry, this one was also accompanied by speculations on the biological ‘‘roles’’ of acute phase glycoproteins. Since the discovery by Polonovski and Jayle in 1938 of Hp and of its complex formation with Hb as well as its determination [4,5], speculations were directed to the nature of the acute phase reaction, its diagnostic value as well as towards the origin of acute phase glycoproteins. As they are rich in carbohydrates, some authors, such as Catchpole and Pirani at the University of Illinois in Chicago, proposed the ‘‘depolymerisation’’ of ground substance ‘‘mucopolysaccharides’’ as a possible source of acute phase, carbohydrate rich glycoproteins [6]. This hypothesis had to be abandoned after the demonstration by Miller [7] and Sarcione [8] of the hepatic origin of acute phase glycoproteins. These arguments were completed and the Catchpole–Pirani hypothesis abandoned after the clarification of the molecular composition of connective tissue matrices, renamed extracellular matrix by Hay [9] and more correctly intercellular matrix by Balazs [10]. Remained the question concerning the function of acute phase glycoproteins, the role of their rich carbohydrate content and their pathological significance. We propose a succinct analysis of these problems in the light of the recent description of the three-dimensional structure of the porcine Hb–Hp complex [1].

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