Maud Menten

Biography

• Born 20 March 1879, Port Lambton, Canada
• 1904 – BA, University of Toronto
• 1904-1905 Demonstrator in physiology in the laboratory of Archibald MacCallum (1858-1934) – founder of the National Research Council of Canada.
• 1907 – MB (bachelor of medicine) from the University of Toronto
• 1907-1909 Fellow at the Rockefeller Institute for Medical Research studying the effect of radium on tumours with with Simon Flexner (1863-1946) and James Wesley Jobling (1876–1961)
• 1909-1911 Research fellow, Western Reserve University, Cleveland studying Hydrogen ions in blood
• 1911 – MD, University of Toronto; one of the first Canadian women to receive a medical doctorate in Canada. Physiology demonstrator in MacCallum’s laboratory.
• 1912 – Research was Menten’s calling, but as a woman she was unable to pursue this further in Canada so she crossed the Atlantic to work with Leonor Michaelis (1875-1949) at the Hospital Am Urban, Berlin
• 1913-1914 Research fellow, Western Reserve University, Cleveland studying Hydrogen ions in blood with George Crile (1864-1943)
• 1916 – PhD in biochemistry, University of Chicago
• 1918-1924 Faculty of the University of Pittsburgh School of Medicine; Demonstrator in pathology (1918); Assistant professor of pathology (1923)
• 1925 – Associate professor of pathology, University of Pittsburgh School of Medicine
• 1926-1950 Pathologist at the Children’s Hospital of Pittsburgh
• 1949 – Professor of pathology, University of Pittsburgh School of Medicine
• 1951-1954 British Columbia Medical Research Institute, Vancouver. Studying the nucleic acid content of the bone marrow of leukaemia patients, using normal and leukaemic mice as animal models
• Canadian Medical Hall of Fame Laureate (1998)
• Died 26 July 1960, Leamington, Canada

Medical Eponyms

Michaelis-Menten equation (1913)

The Michaelis-Menten equation used in textbooks today is derived from the 1903 publications and thesis of work of Victor Henri (1872-1940). This work was cited extensively and amplified and expanded by Michaelis and Menten in their 1913 publication in Biochemische Zietschrift. George Briggs and JBS Haldane in 1925 added the steady state assumption and simplified the final equation. Johnson and Goody provided the full translation and review of the original Michaelis-Menten paper in 2011

Michaelis and Menten studied the enzyme invertase, which breaks down complex sugars (sucrose) into simpler sugars (fructose and glucose). They found that the rate at which glucose and fructose appear depends on:

1. the binding of sucrose to invertase (initial capture);
2. the catalyzed chemical conversion of sucrose into simpler sugars; and
3. the unbinding of fructose and glucose from invertase (final release). 

Enzyme (E) binds reversibly to its substrate (S), creating an enzyme-substrate (ES) complex. This complex breaks down, forming the product (P) and regenerating the free enzyme (E).

According to Michaelis and Menten (1913) the substrate concentration was to be regarded as an important factor controlling the velocity of an enzyme reaction. The velocity (v) of a reaction is related to the substrate concentration (S) by the Michaelis-Menten equation where Vmax is the maximum velocity of the reaction when the enzyme is saturated with substrate. The term K_m is the Michaelis constant which indicates an enzyme’s affinity for its substrate

Key Medical Contributions

1925 – Helen Manning and Menten observed that guinea pigs and rabbits infected with Salmonella and other bacterial infections developed hyperglycaemia. They studied the paratyphoid in rabbits to understand the relationship between the hyperglycaemia and the endotoxins produced by the bacteria. They concluded (1925) that bacterial endotoxins cause a depletion of glycogen reserves. Later confirmed by McCallum in 1973

1944 – Menten and colleagues used sedimentation and electrophoresis to distinguish between haemoglobin variants in 1944 well before the ‘more famous’ and oft quoted work of Linus Pauling (1901-1994) and his work on sickle cell disease (1949). Menten et al proposed that ‘adult and fetal hemoglobins might be differentiated by electrophoretic mobilities, if the variation exists in the protein part of the molecule’

1944 – Histochemical detection of alkaline phosphatase in the kidney. Alkaline phosphatase is widely distributed in different animal tissues, and its importance as a histochemical marker led Menten et al (1944) to develop an azo dye method for the detection of alkaline phosphatase in the kidney, based on detection of the alcoholic product of hydrolysis of the phosphate ester used as the substrate. The Menten-Junge-Green method effectively opened up the field of enzyme histochemistry.

Major Publications

• Macallum AB, Menten ML. On the distribution of chlorides in nerve cells and fibres. Proc Roy Soc Ser B 1906; 77, 165–193
• Menten ML. Experiments on the influence of radium bromide on a carcinomatous tumor of the rat. Monographs on Medical and Allied subjects. Rockefeller Institute for Medical Research 1910; 1: 73-80
• Menten ML. The distribution of fat, chlorides, phosphates, potassium and iron in striated muscle. Transactions of the Canadian Institute. 1910; 8: 403
• Menten ML. The relation of potassium salts and other substances to local anaesthesia of nerves. Am J Physiol 1912; 31(2): 85–93
• Michaelis L, Menten ML. Die Kinetik der Invertinwerkung. Biochemische Zeitschrift, 1913; 49: 333-369. [Johnson KA, Goody RS. The original Michaelis constant: translation of the 1913 Michaelis-Menten paper. Biochemistry. 2011;50(39):8264-8269.]
• Menten ML, Crile GW. Studies on the hydrogen-ion concentration in blood under various abnormal conditions. Am J Physiol 1915; 38(2): 225–232
• Menten ML. The Alkalinity of the Blood in Malignancy and Other Pathological Conditions; Together with Observations on the Relation of the Alkalinity of the Blood to Barometric Pressure. J Cancer Res. 1917; 2(2): 179-211
• Menten ML, Manning HM. Relationship of enteritidis-paratyphoid B infections to hyperglycemia in rabbits. J Infect Dis 1925; 37(5): 400–410
• Menten ML, King CG. The influence of vitamin C level upon resistance to diphtheria toxin II. Production of diffuse hyperplastic arteriosclerosis and degeneration in various organs. J Nutr 1935; 10: 141–155.
• Andersch MA, Wilson DA, Menten ML. Sedimentation Constants and Electrophoretic Mobilities of Adult and Fetal Carbonylhemoglobin. J Biol Chem 1944; 153: 301–305
• Menten ML, Junge J, Green MH. Distribution of Alkaline Phosphatase in Kidney Following the Use of Histochemical Azo Dye Test. Proceedings of the Society for Experimental Biology and Medicine, 1944; 57(1), 82–86.
• Carpenter AM, Polonsky B, Menten ML. Histochemical distribution of glycogen. I. evaluation of methods. AMA Arch Pathol. 1951;51(5):480-485.
• Menten ML, Carpenter AM. Histochemical distribution of glycogen II. In the kidneys of patients with different pathological conditions, especially those with lipoid nephrosis. AMA Arch Pathol. 1951;51(5):486-493.
• Menten ML, Carpenter AM. Histochemical distribution of glycogen. III. In kidneys of leukemic patients. AMA Arch Pathol. 1951;51(5):494-497.
• Menten ML, Willms M, Wright WD. Nucleic acid content of splenic lymphocytes in normal and leukemic mice. Cancer Res 1953; 13: 729–732.
• Menten ML, Willms M. Nucleic acid content of cells of bone marrow aspirated from patients with leukemia. Cancer Res 1953; 13: 733–736.

Controversies

• Name: Maud usually misspelled as Maude;
• Middle name: Leonora but often written as Lenora or Lenore. Birth certificate has no middle initial, this has led to speculation that Leonora is in tribute to Leonor Michaelis; however, her first article published in 1906 already has the middle initial and derivation is likely as a family name.
• Surname: Menten is most commonly misspelled as Menton. Journal articles and even major medical textbooks still list the wrong eponymous term as “Michaelis-Menton equation”

References

Biography

• Stock A, Carpenter A. Prof. Maud Menten. Nature. 1961; 189: 965
• Gjedde A. The emancipation of Miss Menten. J Cereb Blood Flow Metab. 1989;9(2):243-246
• Maud L. Menten, MD. Canadian medial Hall of Fame: 1998
• Skloot R. Some called her Miss Menten. PittMed. 2000: 18-21
• Kumar L. Maud Leonora Menten, MD & PhD: Scientist, Doctor, Female Pioneer. 2013
• Deichmann U, Schuster S, Mazat J-P. Cornish-Bowden A. Commemorating the 1913 Michaelis-Menten paper “Die Kinetik der Invertinwirkung”: three perspectives. FEBS Journal, 2013; 281(2), 435–463
• Moran LA. The mystery of Maud Menten. Sandwalk. 2014
• Bibliography. Menten, Maud L. WorldCat Identities

Eponyms

• Henri V. Lois générales de l’action des diastases. 1903
• Briggs GE, Haldane JB. A Note on the Kinetics of Enzyme Action. Biochem J. 1925;19(2):338-339
• Briggs GE. A Further Note on the Kinetics of Enzyme Action. Biochem J. 1925;19(6):1037-1038.
• Pauling L, Itano HA, Singer SJ, Wells IC. Sickle cell anemia, a molecular disease. Science 1949; 110: 543–548.
• McCallum RE, Berry LJ. Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver-glycogen synthase in mice. Infect Immun 1972; 7: 642–654.
• Johnson KA, Goody RS. The original Michaelis constant: translation of the 1913 Michaelis-Menten paper. Biochemistry. 2011;50(39):8264-8269
• Punekar NS. Henri–Michaelis–Menten Equation. In: ENZYMES: Catalysis, Kinetics and Mechanisms. Springer, Singapore. 2018: 155-176