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Wednesday, 01.04.2020

Thomas A. Ban
Neuropsychopharmacology in Historical Perspective.

Education in the field in the Post-Psychopharmacology Era

Collated 11

 

Joseph Knoll: The discovery of monoamine oxidase (MAO) enzymes

 

 

Herman F. Blascko                 July 17, 2014                          Profiles

Amine oxidase                        June 26, 2014                          Dictionary

Monoamine oxidase                May 22, 2014                          Dictionary

Monoamine oxidase A            August 14, 2014                      Dictionary

Monoamine oxidase B            August 28, 2014                      Dictionary

 

 

Hermann F.  Blaschko

 

       Hermann (Hugh) Felix Blaschko was born January 4, 1900, in Berlin and received his medical degree in 1922 from the University of Berlin. Subsequently, he worked at the Medical Clinic of the University Hospital in Göttingen, Germany, before embarking on a research career in 1925 in Otto Meyerhof’s laboratory in Berlin (Born and Banks 1962).  

       In 1933, Blaschko moved from Germany to England and on the encouragement of Professor Joseph Barcroft began his studies on adrenaline metabolism at the Institute of Physiology in Cambridge. This led to his discovery that it was the same enzyme, he referred to as amine oxidase, and not substrate specific enzymes, as many believed at the time, which metabolized tyramine, dopamine, noradrenaline, adrenaline and aliphatic amines, in general (Blaschko, Richter and Schlossman 1937a; Hare 1928). They also demonstrated the presence of the enzyme in the liver (Blaschko, Richter and Schlossman 1937b).

       In 1938, after Albert Zeller’s separation of diamine oxidase from amine oxidase, the name of Blaschko’s enzyme was changed to monoamine oxidase to indicate that its function is restricted to the oxidative deamination of monoamines.

       Extending his research from the metabolism of adrenaline to the synthesis of catecholamines in 1939, Blaschko described l-DOPA decarboxylase and discovered that it is the enzyme involved in the decarboxylation of levodopa to dopamine. Furthermore, by the mid-1940s Blaschko recognized that tyrosine converts into levodopa, levodopa into dopamine, dopamine into noradrenaline and noradrenaline into adrenaline (Blascho 1952).

       In 1943 Blaschko moved from Barcroft’s Institute of Physiology in Cambridge, to J.H. Burns’ Department of Pharmacology in Oxford. He continued his research with adrenaline and catecholamines and about 10 years later, in 1953, he demonstrated that adrenaline is stored in cytoplasmic particles in vesicles, localized in the membrane of cells which produce it in the adrenal medulla (Blaschko and Welch 1953).  He also recognized that in case of need, adrenaline is driven out from its storage vesicles by an inner force, referred to as “exocytosis” (Blaschko and Muscholl 1972).

       In 1962, in recognition of his contributions, Hermann Blaschko was elected a Fellow of the British Royal Society (FRS). On April 18, 1993, at age 93, Blaschko died in Oxford.

 

References:

Blaschko H. The specific action of l-dopa decarboxylase. Journal of Physiology 1939; 96:50-1.

Blaschko H. Amine oxidase and amine metabolism. Pharmacol Rev 1952; 28: 415-53.

Blaschko H, Muscholl E. Catecholamines. In: Blaschko H, Muscholl E, eds.  Handbuch der experimentellen Pharmakologie. Volume 33. Berlin: Springer Verlag; 1972, pp. 283-335.

Blaschko H, Richter D, Schlossmann H. The inactivation of adrenaline. Journal of Physiology 1937a; 90:1-14.

Blaschko H, Richter D, Schlossmann H. The oxidation of adrenaline and other amines. Biochemical Journal 1937b; 31: 2187-96.

Blaschko H, Welch AD. Localization of adrenaline in cytoplasmic particles of the bovine adrenal medulla. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie 1953; 219: 17-22.

Born GVR, Banks P. Hugh Blaschko. Memoirs of Fellows of the Royal Society 1962; 42: 41-63.

 

July 17, 2014 (Profiles)

 

Amine oxidase

 

       In 1937 Blaschko, Richter and Schlossman demonstrated that tyramine oxidase, the enzyme discovered by Hare in 1928, noradrenaline oxidase and aliphatic amine oxidase was the same enzyme.  They referred to the enzyme as “amine oxidase.”  In the same year, 1937, as Blaschko and his associates demonstrated the presence of “amine oxidase” in the liver, Cecilia Elizabet Mary Pugh and Juda Hirsch Quastel demonstrated the presence of the same enzyme in the brain.  One year later, in 1938, after Albert Zeller’s separation of diamine oxidase from “amine oxidase,” the term was replaced by the term “monoamine oxidase” to indicate that its function is restricted to the oxidative deamination of monoamines.  

 

References:

Blaschko H, Richter D, Schlossman H. The inactivation of adrenaline. J Physiol 1937a; 90: 1-17.

Blaschko H, Richter D, Schlossmann H. The oxidation of adrenaline and other amines. Biochemical Journal 1937b; 31: 2187-96.

Hare MLC. Tyramine oxidase I. A new enzyme system in the liver.  Biochemical Journal 1928; 22:968-79.

Pugh C, Quastel JH. Oxidation of aliphatic amines in brain and other tissues. Biochemcal Journal 1937; 31: 286-91.

Zeller EA. Über den enzymatischen Abbau von Histamin und Diaminen. Helvetica Chimica Acta 1938; 21:881-90.

 

June 26, 2014 (Dictionary)

 

Monoamine oxidase

 

       Monoamine oxidase is the enzyme that metabolizes monoamines by oxidative deamination in the body. The generic name, “monoamine oxidase,” was given to the enzyme by Albert Zeller in 1938 in order to differentiate within “amine oxidase” - shown to be present in 1937 in the liver by Blaschko, Richter and Schlosberg, and in the brain by Pugh and Quastel - the enzyme that metabolizes monoamines from the enzyme that metabolizes diamines in the body. The enzyme is also referred to as “mitochondrial monoamine oxidase” because it is located intracellularly on the outer membrane of mitochondria.    

 

References:

Blaschko H, Richter D, Schlossmann H. The oxidation of adrenaline and other amines. Biochemical Journal 1937; 31: 2187-96.

Pugh C, Quastel JH. Oxidation of aliphatic amines in brain and other tissues. Biochem Journal 1937; 31: 286-91.

Zeller E.A. Über den enyzmatischen Abbau von Histamin und Diaminen. 2. Mitteilung. Helvetica Chimica Acta 1938; 21:880-90.

 

May 22, 2014 (Dictionary)

 

Monoamine oxidase A

 

       Type-A monoamine oxidase (MAO-A) is the form of monoamine oxidase (MAO) that is sensitive to clorgyline.  Clorgyline, 3-(2, 4-dichlorophenoxy)-N-methyl-N-2-ynylpropan-1-amine, is an irreversible MAO inhibitor substance, structurally related to pargyline.  This term was coined and introduced in 1968 by Johnston, to distinguish between clorgyline-sensitive and insensitive forms of monoamine oxidase (MAO) enzymes that he referred to as Type-A monoamine oxidase and Type-B monoamine oxidase, respectively.  MAO-A was found to be present in the neurons, astroglia, gastrointestinal tract, liver and placenta (Neff and Gorodis 1972).  By the early 1970s, it was recognized that MAO-A is primarily responsible for the oxidative deamination of the monoamines serotonin, melatonin, noradrenaline (norepinephrine) and adrenaline (epinephrine), and not only of serotonin, as originally proposed (Costa and Sandler 1972).

 

References:

Costa E, Sandler M, editors. Monoamine Oxidases – New Vistas. Advances in Biochemical Psychopharmacology. Volume 5. New York:  Raven Press; 1972.

Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in human brain. Biochemical Pharmacology 1968; 17: 1285-1297. 

Neff NH, Gorodis C. Neuronal monoamine oxidase: specific types and their rates of formation. Advances Biochemical Psychopharmacology 1972; 5: 2017-23.

 

August 14, 2014 (Dictionary)

 

Monoamine oxidase B

 

       Type-B monoamine oxidase (MAO-B) is the form of monoamine oxidase (MAO) that is insensitive to clorgyline.  Clorgyline, 3-(2, 4-dichlorophenoxy)-N-methyl-N-2-ynylpropan-1-amine, is an irreversible MAO-inhibitor substance, structurally related to pargyline.  The term was coined and introduced in 1968 by Johnston, to distinguish between clorgyline-sensitive and insensitive forms of monoamine oxidase (MAO) enzymes, referred to as Type-A monoamine oxidase and Type-B monoamine oxidase, respectively.  MAO-B was found to be present in the neurons, astroglia and platelets (Neff and Gorodis 1972) and was primarily responsible for the oxidative deamination of beta-phenylethylamine and benzylamine (Costa and Sandler 1972).  In 1971, it was shown that MAO activity progressively increased in the aging brain (Robinson, Davis, Nies et al. 1971) and, by 1980, it was also recognized that this was due entirely to the increase in MAO-B concentrations in brain tissue (Fowler, Wiberg, Oreland et al. 1980).  The first selective MAO-B inhibitor, (-)-deprenyl/selegiline, an (R) –N- methyl-N-(1-phenylpropan-2-yl) prop-2-yn-1-amine, was identified, in1972, by Joseph Knoll and Kalman Magyar.

References:

Costa E, Sandler M, editors. Monoamine Oxidases – New Vistas. Advances in Biochemical Psychopharmacology. Volume 5. New York:  Raven Press; 1972.

Fowler CJ, Wiberg A, Oreland L, Marcusson J, Winblad B. The effect of age on the activity and molecular properties of human brain monoamine oxidase. Journal Neural Transmission 1980; 49:1-20.

Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in human brain. Biochemical Pharmacology 1968; 17:1285-97.

Knoll J, Magyar K. Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychoharmacol 1972;5:393-408.

Neff NH, Gorodis C. Neuronal monoamine oxidase: specific types and their rates of formation. Advances Biochemical Psychopharmacology 1972;5:2017-23.

Robinson DS, Davis JM, Nies A, Ravaris C.L, Sylwester D. Relation of sex and aging to monoamine oxidase activity in human brain, plasma and platelets. Archives General Psychiatry 1971;24:536-9.

 

August 28, 2014 (Dictionary)