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Porphyrin Metabolism in the Anemias: The George Richards Minot Lecture

Porphyrin Metabolism in the Anemias: The George Richards Minot Lecture Abstract I count it a special privilege and honor to have been invited to give the sixth George Richards Minot Lecture of this section. I have a strong personal feeling about this because over a period of quite a number of years George Minot stimulated and aided my research and was most generous with his advice and friendship on many occasions. Among many fine and interesting qualities, one of the most appealing that he had, in my opinion, was that of helping and encouraging young men along the tortuous path of medical research. He is famous for his notes to young investigators, often penny post cards in his own handwriting, telling them of his interest in one of their recent papers. He was considerate in his praise, just and meticulous in his criticism. His use of the English language was never dull, and it was often quaint and amusing. In the References 1. Phenylhydrazine alone causes a moderate increase in excretion of coproporphyrin I in the urine of rabbits and an increased relative concentration of this porphyrin in the circulating erythrocytes (Ref. 32 and unpublished data of H. M. Wikoff and S. Schwartz). 2. It is recognized that significant amounts of this porphyrin may have escaped detection, as the Type I isomer, which predominates, crystal- lizes much more readily, and smaller amounts of Type III, (or even II or IV) may have been left in the mother liquor. 3. With Dr. Marie Berg and Miss Ruth Cardinal. 4. This study is in progress with Dr. Marie Berg. 5. Castle, W. B.: The Contributions of George Richards Minot to Experimental Medicine (George R. Minot Lecture) , New England J. Med. 247:585, 1952.Crossref 6. Schmid, R.; Schwartz, S., and Watson, C. J.: Porphyrin Content of Bone Marrow and Liver in the Various Forms of Porphyria , A. M. A. Arch. Int. Med. 93:167, 1954.Crossref 7. Shemin, D.: The Succinate-Glycine Cycle: The Role of δ-Amino-Levulinic Acid in Porphyrin Synthesis , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 4. 8. Schwartz, S.; Keprios, M., and Schmid, R.: Experimental Porphyria: II. Type Produced by Lead, Phenylhydrazine and Light , Proc. Soc. Exper. Biol. & Med. 79:463, 1952. 9. Schmid, R.; Schwartz, S., and Watson, C. J.: Porphyrins in the Bone Marrow and Circulating Erythrocytes in Experimental Anemias , Proc. Soc. Exper. Biol. & Med. 75:705, 1950. 10. Shemin, D., and Rittenberg, D.: The Utilization of Glycine for the Synthesis of a Porphyrin , J. Biol. Chem. 159:567, 1945. 11. Shemin, D., and Wittenberg, J.: The Mechanism of Porphyrin Formation: The Rôle of the Tricarboxylic Acid Cycle , J. Biol. Chem. 192:315, 1951. 12. Shemin, D., and Kumin, S.: The Mechanism of Porphyrin Formation: The Formation of a Succinyl Intermediate from Succinate , J. Biol. Chem. 198:827, 1952. 13. Cookson, G. H., and Rimington, C.: Porphobilinogen: Chemical Constitution , Nature, London 171:875, 1953. 14. Cookson, G. H., and Rimington, C.: Porphobilinogen. Biochem. J. 51:476, 1954. 15. Neuberger, A., and Scott, J. J.: Aminolævulinic Acid and Porphyrin Biosynthesis , Nature, London 172:1093, 1953. 16. Bashour, F.: Lead Poisoning , Bull. Univ. Minnesota Hosp. & Minnesota M. Found. 26:423, 1955. 17. Bashour, F. A.: Urinary Uroporphyrin, Porphobilinogen and Coproporphyrin Excretion in Lead-Exposed Workers , J. Lab. & Clin. Med. 44:764, 1954. 18. Falk, J. E.: Haem and Porphyrin Formation from Glycine, δ-Aminolaevulic Acid and Porphobilinogen , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 63. 19. Dresel, E. I. B.: The Role of Some Porphyrins and Porphyrin Precursors in the Biosynthesis of Haem , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 72. 20. Schwartz, S., and Ikeda, K.: Studies of Porphyrin Synthesis and Interconversion with Special Reference to Certain Green Porphyrins in Animals with Experimental Hepatic Porphyria , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 209. 21. Watson, C. J.: Porphyria , Advances Int. Med. 6:235, 1954. 22. Eriksen, L.: Relation of Free Erythrocyte Porphyrins to Haemoglobin Biosynthesis , London, J. & A. Churchill, Ltd., 1955, p. 185. 23. Grinstein, M.; Kamen, M. D.; Wikoff, H. M., and Moore, C. V.: Isotopic Studies of Porphyrin and Hemoglobin Metabolism: I. Biosynthesis of Coproporphyrin I and Its Relationship to Hemoglobin Metabolism , J. Biol. Chem. , 182:715, 1950. 24. Watson, C. J.: The Erythrocyte Coproporphyrin: Variation in Respect to Erythrocyte Protoporphyrin and Reticulocytes in Certain of the Anemias , Arch. Int. Med. 86:797, 1950. 25. Salomon, K.; Richmond, J. E., and Altman. K. I.: Tetrapyrrole Precursors of Protoporphyrin IX: I. Uroporphyrin III , J. Biol. Chem. 196:463, 1952. 26. Shemin, D., in Discussion of paper by E. I. B. Dresel, in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. B. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 63. 27. Neve, R.; Labbe, L., and Aldrich, R.: Reduced Uroporphyrin III in the Biosynthesis of Heme , J. Am. Chem. Soc. 78:691, 1956. 28. Bashour, F.: The Conversion of Reduced Uroporphyrin I to Coproporphyrin and Protoporphyrin by Dog Liver Homogenate , J. Clin. Invest. 35:689, 1956. 29. Watson, C. J.; DeMello, R. P.; Schwartz, S.; Hawkinson, V., and Bossenmaier, I.: Porphyrin Chromogens or Precursors in Urine Blood, Bile and Feces , J. Lab. & Clin. Med. 37:831, 1951. 30. Rimington, C.: An Enzymic Theory of Haemopoiesis , Compt. rend. trav. lab. Carlsberg, série. chim. 22:454, 1938. 31. Zieve, L.; Hill, E.; Schwartz, S., and Watson, C. J.: Normal Limits of Urinary Coproporphyrin Excretion Determined by an Improved Method , J. Lab. & Clin. Med. 41:663, 1953. 32. Watson, C. J.; Hawkinson, V., and Sutherland, D.: Studies of Coproporphyrin: I. The per Diem Excretion and Isomer Distribution of Coproporphyrin in Normal Human Urine , J. Clin. Invest. 28:447, 1949. 33. Fischer, H.: Über das Urinporphyrin , Ztschr. physiol. Chem. 95:34, 1915. 34. Fischer, H.: Über das Kotporphyrin , Ztschr. physiol. Chem. 96:148, 1915. 35. Schmid, R.; Hanson, B., and Schwartz, S.: Experimental Porphyria: I. Isolation of Uroporphyrin I from Bone Marrow of Lead Poisoned Rabbits , Proc. Soc. Exper. Biol. & Med. 79:459, 1952. 36. Schwartz, S., and Wikoff, H. M.: The Relation of Erythrocyte Coproporphyrin and Protoporphyrin to Erythropoiesis , J. Biol. Chem. 194:563, 1952. 37. Hardy, H. L.; Elkins, H. B.; Ruotolo, B. P. W.; Quimby, J., and Baker, W. H.: Use of Monocalcium Disodium Ethylene Diamine Tetra-Acetate in Lead Poisoning , J. A. M. A. 154:1171, 1954. 38. Schwartz, S.; Hawkinson, V.; Cohen, S., and Watson, C. J.: A Micromethod for the Quantitative Determination of the Urinary Coproporphyrin Isomers (I and III) , J. Biol. Chem. 168:133, 1947. 39. Chu, T. C.; Green, Sister A. A., and Chu, E. J.: Paper Chromatography of Methyl Esters of Porphyrins , J. Biol. Chem. 190:643, 1951. 40. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: II. The Isolation of a Hitherto Undescribed Porphyrin Occurring with an Increased Amount of Coproporphyrin I in the Feces of a Case of Hemolytic Jaundice , J. Clin. Invest. 14:110, 1935. 41. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: III. The Isolation of Coproporphyrin I from the Feces of Untreated Cases of Pernicious Anemia , J. Clin. Invest. 14:116, 1935. 42. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: V. Porphyrins of the Feces , J. Clin. Invest. 16:383, 1937. 43. Dobriner, K.: The Excretion of Coproporphyrin I Following Hemorrhage in Dogs , J. Clin. Invest. 17:105, 1938. 44. Dobriner, K., and Rhoads, C. P.: The Metabolism of Blood Pigments in Pernicious Anemia , J. Clin. Invest. 17:95, 1938. 45. Schwartz, S.; Glickman, M.; Hunter, R., and Wallace, J.: Studies of Porphyrin Metabolism: III. The Relation of Erythropoiesis to the Excretion of Coproporphyrin by Dogs and Rabbits, and to the Concentration of Coproporphyrin and Protoporphyrin in Rabbit Erythrocytes, Biological Effects of External X and Gamma Radiation, edited by R. E. Zirkle, Atomic Energy Commission, August, 1956, Pt. 2, p. 187. 46. London, I. M.; Shemin, D., and Rittenberg, D.: Synthesis of Heine in Vitro by the Immature Non-Nucleated Mammalian Erythrocyte , J. Biol. Chem. 183:749, 1950. 47. Bomford, R. R., and Rhoads, C. P.: Refractory anaemia: Aetiology and Treatment , Quart. J. Med. 10:235, 1941. 48. Watson, C. J., and Larson, E. A.: The Urinary Coproporphyrins in Health and Disease , Physiol. Rev. 27:478, 1947. 49. Fischer, H.: Über Hämin und Porphyrine , Verhandl. deutsch. Gesellsch. inn. Med. 45:7, 1933. 50. Schwartz, S.; Rosenblum, C.; Miller, I. M., and Ikeda, K.: To be published. 51. Bashour, F.: To be published. 52. Lowry, P.: Unpublished data. 53. Comfort, A.; Moore, H., and Weatherall, M.: Normal Human Urinary Porphyrins , Biochem. J. 58:177, 1954. 54. Shemin, D.; Corcoran, J. W.; Rosenblum, C., and Miller, I.: Biosynthesis of the Porphyrinlike Moiety of Vitamin B12 , Science 124:272, 1956. 55. Goldberg, A.; Ashenbrucker, H.; Cartwright, G. E., and Wintrobe, M. M.; Studies on the Biosynthesis of Heme in Vitro by Avian Erythrocytes , Blood 11:821, 1956. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png A.M.A. Archives of Internal Medicine American Medical Association

Porphyrin Metabolism in the Anemias: The George Richards Minot Lecture

A.M.A. Archives of Internal Medicine , Volume 99 (3) – Mar 1, 1957

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Copyright © 1957 American Medical Association. All Rights Reserved.
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0888-2479
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Abstract

Abstract I count it a special privilege and honor to have been invited to give the sixth George Richards Minot Lecture of this section. I have a strong personal feeling about this because over a period of quite a number of years George Minot stimulated and aided my research and was most generous with his advice and friendship on many occasions. Among many fine and interesting qualities, one of the most appealing that he had, in my opinion, was that of helping and encouraging young men along the tortuous path of medical research. He is famous for his notes to young investigators, often penny post cards in his own handwriting, telling them of his interest in one of their recent papers. He was considerate in his praise, just and meticulous in his criticism. His use of the English language was never dull, and it was often quaint and amusing. In the References 1. Phenylhydrazine alone causes a moderate increase in excretion of coproporphyrin I in the urine of rabbits and an increased relative concentration of this porphyrin in the circulating erythrocytes (Ref. 32 and unpublished data of H. M. Wikoff and S. Schwartz). 2. It is recognized that significant amounts of this porphyrin may have escaped detection, as the Type I isomer, which predominates, crystal- lizes much more readily, and smaller amounts of Type III, (or even II or IV) may have been left in the mother liquor. 3. With Dr. Marie Berg and Miss Ruth Cardinal. 4. This study is in progress with Dr. Marie Berg. 5. Castle, W. B.: The Contributions of George Richards Minot to Experimental Medicine (George R. Minot Lecture) , New England J. Med. 247:585, 1952.Crossref 6. Schmid, R.; Schwartz, S., and Watson, C. J.: Porphyrin Content of Bone Marrow and Liver in the Various Forms of Porphyria , A. M. A. Arch. Int. Med. 93:167, 1954.Crossref 7. Shemin, D.: The Succinate-Glycine Cycle: The Role of δ-Amino-Levulinic Acid in Porphyrin Synthesis , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 4. 8. Schwartz, S.; Keprios, M., and Schmid, R.: Experimental Porphyria: II. Type Produced by Lead, Phenylhydrazine and Light , Proc. Soc. Exper. Biol. & Med. 79:463, 1952. 9. Schmid, R.; Schwartz, S., and Watson, C. J.: Porphyrins in the Bone Marrow and Circulating Erythrocytes in Experimental Anemias , Proc. Soc. Exper. Biol. & Med. 75:705, 1950. 10. Shemin, D., and Rittenberg, D.: The Utilization of Glycine for the Synthesis of a Porphyrin , J. Biol. Chem. 159:567, 1945. 11. Shemin, D., and Wittenberg, J.: The Mechanism of Porphyrin Formation: The Rôle of the Tricarboxylic Acid Cycle , J. Biol. Chem. 192:315, 1951. 12. Shemin, D., and Kumin, S.: The Mechanism of Porphyrin Formation: The Formation of a Succinyl Intermediate from Succinate , J. Biol. Chem. 198:827, 1952. 13. Cookson, G. H., and Rimington, C.: Porphobilinogen: Chemical Constitution , Nature, London 171:875, 1953. 14. Cookson, G. H., and Rimington, C.: Porphobilinogen. Biochem. J. 51:476, 1954. 15. Neuberger, A., and Scott, J. J.: Aminolævulinic Acid and Porphyrin Biosynthesis , Nature, London 172:1093, 1953. 16. Bashour, F.: Lead Poisoning , Bull. Univ. Minnesota Hosp. & Minnesota M. Found. 26:423, 1955. 17. Bashour, F. A.: Urinary Uroporphyrin, Porphobilinogen and Coproporphyrin Excretion in Lead-Exposed Workers , J. Lab. & Clin. Med. 44:764, 1954. 18. Falk, J. E.: Haem and Porphyrin Formation from Glycine, δ-Aminolaevulic Acid and Porphobilinogen , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 63. 19. Dresel, E. I. B.: The Role of Some Porphyrins and Porphyrin Precursors in the Biosynthesis of Haem , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 72. 20. Schwartz, S., and Ikeda, K.: Studies of Porphyrin Synthesis and Interconversion with Special Reference to Certain Green Porphyrins in Animals with Experimental Hepatic Porphyria , in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. E. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 209. 21. Watson, C. J.: Porphyria , Advances Int. Med. 6:235, 1954. 22. Eriksen, L.: Relation of Free Erythrocyte Porphyrins to Haemoglobin Biosynthesis , London, J. & A. Churchill, Ltd., 1955, p. 185. 23. Grinstein, M.; Kamen, M. D.; Wikoff, H. M., and Moore, C. V.: Isotopic Studies of Porphyrin and Hemoglobin Metabolism: I. Biosynthesis of Coproporphyrin I and Its Relationship to Hemoglobin Metabolism , J. Biol. Chem. , 182:715, 1950. 24. Watson, C. J.: The Erythrocyte Coproporphyrin: Variation in Respect to Erythrocyte Protoporphyrin and Reticulocytes in Certain of the Anemias , Arch. Int. Med. 86:797, 1950. 25. Salomon, K.; Richmond, J. E., and Altman. K. I.: Tetrapyrrole Precursors of Protoporphyrin IX: I. Uroporphyrin III , J. Biol. Chem. 196:463, 1952. 26. Shemin, D., in Discussion of paper by E. I. B. Dresel, in Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism , edited by G. B. W. Wolstenholme and E. C. P. Millar, London, J. & A. Churchill, Ltd., 1956, p. 63. 27. Neve, R.; Labbe, L., and Aldrich, R.: Reduced Uroporphyrin III in the Biosynthesis of Heme , J. Am. Chem. Soc. 78:691, 1956. 28. Bashour, F.: The Conversion of Reduced Uroporphyrin I to Coproporphyrin and Protoporphyrin by Dog Liver Homogenate , J. Clin. Invest. 35:689, 1956. 29. Watson, C. J.; DeMello, R. P.; Schwartz, S.; Hawkinson, V., and Bossenmaier, I.: Porphyrin Chromogens or Precursors in Urine Blood, Bile and Feces , J. Lab. & Clin. Med. 37:831, 1951. 30. Rimington, C.: An Enzymic Theory of Haemopoiesis , Compt. rend. trav. lab. Carlsberg, série. chim. 22:454, 1938. 31. Zieve, L.; Hill, E.; Schwartz, S., and Watson, C. J.: Normal Limits of Urinary Coproporphyrin Excretion Determined by an Improved Method , J. Lab. & Clin. Med. 41:663, 1953. 32. Watson, C. J.; Hawkinson, V., and Sutherland, D.: Studies of Coproporphyrin: I. The per Diem Excretion and Isomer Distribution of Coproporphyrin in Normal Human Urine , J. Clin. Invest. 28:447, 1949. 33. Fischer, H.: Über das Urinporphyrin , Ztschr. physiol. Chem. 95:34, 1915. 34. Fischer, H.: Über das Kotporphyrin , Ztschr. physiol. Chem. 96:148, 1915. 35. Schmid, R.; Hanson, B., and Schwartz, S.: Experimental Porphyria: I. Isolation of Uroporphyrin I from Bone Marrow of Lead Poisoned Rabbits , Proc. Soc. Exper. Biol. & Med. 79:459, 1952. 36. Schwartz, S., and Wikoff, H. M.: The Relation of Erythrocyte Coproporphyrin and Protoporphyrin to Erythropoiesis , J. Biol. Chem. 194:563, 1952. 37. Hardy, H. L.; Elkins, H. B.; Ruotolo, B. P. W.; Quimby, J., and Baker, W. H.: Use of Monocalcium Disodium Ethylene Diamine Tetra-Acetate in Lead Poisoning , J. A. M. A. 154:1171, 1954. 38. Schwartz, S.; Hawkinson, V.; Cohen, S., and Watson, C. J.: A Micromethod for the Quantitative Determination of the Urinary Coproporphyrin Isomers (I and III) , J. Biol. Chem. 168:133, 1947. 39. Chu, T. C.; Green, Sister A. A., and Chu, E. J.: Paper Chromatography of Methyl Esters of Porphyrins , J. Biol. Chem. 190:643, 1951. 40. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: II. The Isolation of a Hitherto Undescribed Porphyrin Occurring with an Increased Amount of Coproporphyrin I in the Feces of a Case of Hemolytic Jaundice , J. Clin. Invest. 14:110, 1935. 41. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: III. The Isolation of Coproporphyrin I from the Feces of Untreated Cases of Pernicious Anemia , J. Clin. Invest. 14:116, 1935. 42. Watson, C. J.: Concerning the Naturally Occurring Porphyrins: V. Porphyrins of the Feces , J. Clin. Invest. 16:383, 1937. 43. Dobriner, K.: The Excretion of Coproporphyrin I Following Hemorrhage in Dogs , J. Clin. Invest. 17:105, 1938. 44. Dobriner, K., and Rhoads, C. P.: The Metabolism of Blood Pigments in Pernicious Anemia , J. Clin. Invest. 17:95, 1938. 45. Schwartz, S.; Glickman, M.; Hunter, R., and Wallace, J.: Studies of Porphyrin Metabolism: III. The Relation of Erythropoiesis to the Excretion of Coproporphyrin by Dogs and Rabbits, and to the Concentration of Coproporphyrin and Protoporphyrin in Rabbit Erythrocytes, Biological Effects of External X and Gamma Radiation, edited by R. E. Zirkle, Atomic Energy Commission, August, 1956, Pt. 2, p. 187. 46. London, I. M.; Shemin, D., and Rittenberg, D.: Synthesis of Heine in Vitro by the Immature Non-Nucleated Mammalian Erythrocyte , J. Biol. Chem. 183:749, 1950. 47. Bomford, R. R., and Rhoads, C. P.: Refractory anaemia: Aetiology and Treatment , Quart. J. Med. 10:235, 1941. 48. Watson, C. J., and Larson, E. A.: The Urinary Coproporphyrins in Health and Disease , Physiol. Rev. 27:478, 1947. 49. Fischer, H.: Über Hämin und Porphyrine , Verhandl. deutsch. Gesellsch. inn. Med. 45:7, 1933. 50. Schwartz, S.; Rosenblum, C.; Miller, I. M., and Ikeda, K.: To be published. 51. Bashour, F.: To be published. 52. Lowry, P.: Unpublished data. 53. Comfort, A.; Moore, H., and Weatherall, M.: Normal Human Urinary Porphyrins , Biochem. J. 58:177, 1954. 54. Shemin, D.; Corcoran, J. W.; Rosenblum, C., and Miller, I.: Biosynthesis of the Porphyrinlike Moiety of Vitamin B12 , Science 124:272, 1956. 55. Goldberg, A.; Ashenbrucker, H.; Cartwright, G. E., and Wintrobe, M. M.; Studies on the Biosynthesis of Heme in Vitro by Avian Erythrocytes , Blood 11:821, 1956.

Journal

A.M.A. Archives of Internal MedicineAmerican Medical Association

Published: Mar 1, 1957

References