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The international union of biochemistry committee on education textbook donation program
32 lation ie metabolic and respiratory acidosis and alkalosis with respiratory and/or renal compensation. (2) The hemoglobin system - - the effect of the allosteric behavior of the hemoglobin molecule on blood buffering and on the availability of oxygen for catabolism: positive homotropic effects on oxygen interaction and negative heterotropic effects on H+/CO2 interaction (the Bohr effect). (3) Integration of the buffering systems.
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Discussion The bicarbonate buffer system is discussed soon after the study of the central metabolic pathways. Its inefficiency as a physiological buffer if operating in a closed system, and its efficiency as an open system, is illustrated by the application of the Henderson-Hasselbalch equation. After analyzing the acid-base regulation process, the deviations are presented.1 Metabolic acidosis deserves special attention since metabolic intermediaries such as lactic, acetoacetic and hydroxybutyric acids are frequently present in the blood. The production of these acids during conditions of metabolic stress such as anaerobic exercise or diabetes mellitus can be included for additional discussion. 2 The hemoglobin molecule is firstly described from the perspective of its action as a physiological buffer. The Henderson-Hasselbalch equation is employed to establish the ratio between acid and base species for deoxyhemoglobin (pKa 6.2) and oxyhemoglobin (pKa 7.7) at pH 7.4. The relation of this with the capture and release of H + ions by hemoglobin in tissues and lung respectively, is emphasized. 3 The cooperative binding of oxygen by hemoglobin is examined by the use of the Hill equation and discussed in terms of positive homotropic effect for the hemoglobin-oxygen interaction. 4 The Hill equation can also be applied to the study of the functional differences between hemoglobin and myoglobin,4 and the altered oxygen binding properties of abnormal human hemoglobins. 5 Figure 1 is a simplified scheme for the integrated process: hemoglobin molecules arrive at active metabolic tissues predominantly in an oxygenated non-protonated form and releases the oxygen. The hemoglobin, then behaving as a weak acid, captures the H ÷ ions derived from metabolism. Arriving in the lung, it captures oxygen and releases H ÷ ions, now behaving as a stronger acid) This process, the main one responsible for the elimination of CO2 derived from metabolism, can be discussed in terms of the negative heterotropic effect of H ÷ ions on hemoglobin-oxygen interaction. 4 It should be stressed that COz has the same negative heterotropic effect as H + ions. The role of 2,3-diphosphoglycerate (DPG) on the oxygen binding properties of hemoglobin also can be included in the discussion. 4 In the case of medical students, pathological aspects such as the deviations of acid-base regulation can be emphasised. The analysis of clinical cases 6 is recommended as an applied approach for these students.
Acknowledgements We thank Dr Ana Isabel de Assis for reading the manuscript.
BIOCHEMICAL EDUCATION 18(1) 1990
~' HzO, CO 2
Oz metabolism ATP~, HzO" C 0 2 0.05 --
H+:i¢ :-~-H CO 3
o95
I LUNG
Figure 1 A simplified scheme for the interaction between bicarbonate and hemoglobin in the respiration process. The numbers represent the molar fractions of acid~base pairs for bicarbonate, deoxyhemoglobin and oxyhemoglobin buffers at p H 7.4. Continuous arrows represent the preferential course in the acid-base regulation condition and discontinuous arrows represent metabolic acidosis References 1Masoro, E J and Siegel, P D (1977) 'Acid-Base Regulation' (Second Edition) W B Saunders, Philadelphia 2White, D A, Middleton, B and Baxter, M (1984) 'Hormones and Metabolic Control', Edward Arnold, London, pp 27-47 3Segel, I H (1976) 'Biochemical Calculations' (Second Edition) John Wiley & Sons 4Stryer, L (1988) 'Biochemistry' (Third Edition W H Freeman & Co, New York, pp 143-176 5Smith, E L, Hill, R L, Lehman, I R, Lefkowitz, R J, Handler, P and White, A (1983) 'Principles of Biochemistry - - Mammalian Biochemistry' (Seventh Edition) McGraw-Hill, pp 100-140 6Davenport, H W (1969) 'The ABC of Acid-Base Chemistry' (Fifth Edition) University of Chicago
The International Union of Biochemistry Committee on Education Textbook Donation Program Modest grants have recently been received towards this Program from The Biochemical Society (UK), the Japanese Biochemical Society, the International Council for Scientific Unions and the International Union of Biochemistry. The Program aims to provide Departments of Biochemistry in developing countries with some copies of recent textbooks of Biochemistry, Molecular Biology and related subjects for use by faculty and students in such departments. Requests for assistance through this Program should be made by department heads, and should be accompanied by a brief description of the teaching responsibilities of the department, the number of students and faculty, and such other information as constitutes a basis for the request. Requests should be directed to Professor F Vella, Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W0, Canada (Fax (306) 966-8718)
TISSUE
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.@ .@o2X
Discussion The bicarbonate buffer system is discussed soon after the study of the central metabolic pathways. Its inefficiency as a physiological buffer if operating in a closed system, and its efficiency as an open system, is illustrated by the application of the Henderson-Hasselbalch equation. After analyzing the acid-base regulation process, the deviations are presented.1 Metabolic acidosis deserves special attention since metabolic intermediaries such as lactic, acetoacetic and hydroxybutyric acids are frequently present in the blood. The production of these acids during conditions of metabolic stress such as anaerobic exercise or diabetes mellitus can be included for additional discussion. 2 The hemoglobin molecule is firstly described from the perspective of its action as a physiological buffer. The Henderson-Hasselbalch equation is employed to establish the ratio between acid and base species for deoxyhemoglobin (pKa 6.2) and oxyhemoglobin (pKa 7.7) at pH 7.4. The relation of this with the capture and release of H + ions by hemoglobin in tissues and lung respectively, is emphasized. 3 The cooperative binding of oxygen by hemoglobin is examined by the use of the Hill equation and discussed in terms of positive homotropic effect for the hemoglobin-oxygen interaction. 4 The Hill equation can also be applied to the study of the functional differences between hemoglobin and myoglobin,4 and the altered oxygen binding properties of abnormal human hemoglobins. 5 Figure 1 is a simplified scheme for the integrated process: hemoglobin molecules arrive at active metabolic tissues predominantly in an oxygenated non-protonated form and releases the oxygen. The hemoglobin, then behaving as a weak acid, captures the H ÷ ions derived from metabolism. Arriving in the lung, it captures oxygen and releases H ÷ ions, now behaving as a stronger acid) This process, the main one responsible for the elimination of CO2 derived from metabolism, can be discussed in terms of the negative heterotropic effect of H ÷ ions on hemoglobin-oxygen interaction. 4 It should be stressed that COz has the same negative heterotropic effect as H + ions. The role of 2,3-diphosphoglycerate (DPG) on the oxygen binding properties of hemoglobin also can be included in the discussion. 4 In the case of medical students, pathological aspects such as the deviations of acid-base regulation can be emphasised. The analysis of clinical cases 6 is recommended as an applied approach for these students.
Acknowledgements We thank Dr Ana Isabel de Assis for reading the manuscript.
BIOCHEMICAL EDUCATION 18(1) 1990
~' HzO, CO 2
Oz metabolism ATP~, HzO" C 0 2 0.05 --
H+:i¢ :-~-H CO 3
o95
I LUNG
Figure 1 A simplified scheme for the interaction between bicarbonate and hemoglobin in the respiration process. The numbers represent the molar fractions of acid~base pairs for bicarbonate, deoxyhemoglobin and oxyhemoglobin buffers at p H 7.4. Continuous arrows represent the preferential course in the acid-base regulation condition and discontinuous arrows represent metabolic acidosis References 1Masoro, E J and Siegel, P D (1977) 'Acid-Base Regulation' (Second Edition) W B Saunders, Philadelphia 2White, D A, Middleton, B and Baxter, M (1984) 'Hormones and Metabolic Control', Edward Arnold, London, pp 27-47 3Segel, I H (1976) 'Biochemical Calculations' (Second Edition) John Wiley & Sons 4Stryer, L (1988) 'Biochemistry' (Third Edition W H Freeman & Co, New York, pp 143-176 5Smith, E L, Hill, R L, Lehman, I R, Lefkowitz, R J, Handler, P and White, A (1983) 'Principles of Biochemistry - - Mammalian Biochemistry' (Seventh Edition) McGraw-Hill, pp 100-140 6Davenport, H W (1969) 'The ABC of Acid-Base Chemistry' (Fifth Edition) University of Chicago
The International Union of Biochemistry Committee on Education Textbook Donation Program Modest grants have recently been received towards this Program from The Biochemical Society (UK), the Japanese Biochemical Society, the International Council for Scientific Unions and the International Union of Biochemistry. The Program aims to provide Departments of Biochemistry in developing countries with some copies of recent textbooks of Biochemistry, Molecular Biology and related subjects for use by faculty and students in such departments. Requests for assistance through this Program should be made by department heads, and should be accompanied by a brief description of the teaching responsibilities of the department, the number of students and faculty, and such other information as constitutes a basis for the request. Requests should be directed to Professor F Vella, Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W0, Canada (Fax (306) 966-8718)