Herman Kalckar
Encyclopedia
Herman Moritz Kalckar was a Danish biochemist who pioneered the study of cellular respiration
. Trained as a medical doctor at the University of Copenhagen
, Kalckar then conducted research for his Ph. D. in Ejnar Lundsgaard's (1899–1968) physiology laboratory, work which helped establish a fundamental biochemical paradigm (i.e. "oxidative phosphorylation"). During this period, Lundsgaard was preoccupied as physiology department chair, consequently Fritz Albert Lipmann
, who had recently fled Germany, served as Kalckar's research mentor. Later, Kalckar and Lipmann both independently developed concepts of a "high energy bond," which Lipmann expressed as "~P," and ATP as a universal "energy carrier."
Kalckar was fortunate to be working at an important period in biochemistry's evolution. The biochemical community was in the process of demonstrating the chemical reactions involved in breakdown of foodstuffs essential for growth. At the same time, physiologists were demonstrating the involvement of some of these reactions various physiological processes, e.g. muscle contraction. Kalckar's breakthrough work was the demonstration that organic compounds were phosphorylated during metabolic processes involving oxygen consumption; oxygen consumption was linked to organic compound phosphorylation, a process now known as oxidative phosphorylation. His key experiment demonstrated that in frog muscles where glycolysis
had been inhibited
with iodoacetate
, muscular contraction continued for a short period using phosphocreatine
as a source of energy. This work suggested for the first time that phosphate compounds acted as a link between catabolism
and anabolism
.
Upon completing his doctoral studies, Kalckar came to the United States on a Rockefeller research fellowship, planning to spend a year at the California Institute of Technology (Caltech). Enroute to the west coast, Kalckar visited the Cori lab in St. Louis, where he became friends with Sidney Colowick; the two later collaborated to work on the enzyme adenylate kinase
in 1942, which they purified from muscle extracts. Further work on nucleotide
metabolism allowed him to identify nucleoside phosphorylase, a key enzyme in nucleotide salvage pathways.
Moving on from nucleotides, Kalckar switched his attention to the enzymes involved in galactose
metabolism. Here, he characterised galactose-1-phosphate uridylyltransferase
and identified the cause of the human metabolic disease galactosemia
as a defect in this enzyme.
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...
. Trained as a medical doctor at the University of Copenhagen
University of Copenhagen
The University of Copenhagen is the oldest and largest university and research institution in Denmark. Founded in 1479, it has more than 37,000 students, the majority of whom are female , and more than 7,000 employees. The university has several campuses located in and around Copenhagen, with the...
, Kalckar then conducted research for his Ph. D. in Ejnar Lundsgaard's (1899–1968) physiology laboratory, work which helped establish a fundamental biochemical paradigm (i.e. "oxidative phosphorylation"). During this period, Lundsgaard was preoccupied as physiology department chair, consequently Fritz Albert Lipmann
Fritz Albert Lipmann
Fritz Albert Lipmann FRS was a German-American biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded half the Nobel Prize in Physiology or Medicine in 1953 .Lipmann was born in Königsberg, Germany to a Jewish family.Lipmann...
, who had recently fled Germany, served as Kalckar's research mentor. Later, Kalckar and Lipmann both independently developed concepts of a "high energy bond," which Lipmann expressed as "~P," and ATP as a universal "energy carrier."
Kalckar was fortunate to be working at an important period in biochemistry's evolution. The biochemical community was in the process of demonstrating the chemical reactions involved in breakdown of foodstuffs essential for growth. At the same time, physiologists were demonstrating the involvement of some of these reactions various physiological processes, e.g. muscle contraction. Kalckar's breakthrough work was the demonstration that organic compounds were phosphorylated during metabolic processes involving oxygen consumption; oxygen consumption was linked to organic compound phosphorylation, a process now known as oxidative phosphorylation. His key experiment demonstrated that in frog muscles where glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
had been inhibited
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
with iodoacetate
Iodoacetate
Iodoacetic acid is a derivative of acetic acid. It is a toxic compound, because, like many alkyl halides, it is an alkylating agent. It reacts with cysteine residues in proteins...
, muscular contraction continued for a short period using phosphocreatine
Phosphocreatine
Phosphocreatine, also known as creatine phosphate or PCr , is a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle and brain.-Chemistry:...
as a source of energy. This work suggested for the first time that phosphate compounds acted as a link between catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
and anabolism
Anabolism
Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite...
.
Upon completing his doctoral studies, Kalckar came to the United States on a Rockefeller research fellowship, planning to spend a year at the California Institute of Technology (Caltech). Enroute to the west coast, Kalckar visited the Cori lab in St. Louis, where he became friends with Sidney Colowick; the two later collaborated to work on the enzyme adenylate kinase
Adenylate kinase
Adenylate kinase is a phosphotransferase enzyme that catalyzes the interconversion of adenine nucleotides, and plays an important role in cellular energy homeostasis.-Substrate and products:...
in 1942, which they purified from muscle extracts. Further work on nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
metabolism allowed him to identify nucleoside phosphorylase, a key enzyme in nucleotide salvage pathways.
Moving on from nucleotides, Kalckar switched his attention to the enzymes involved in galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
metabolism. Here, he characterised galactose-1-phosphate uridylyltransferase
Galactose-1-phosphate uridylyltransferase
Galactose-1-phosphate uridylyltransferase is an enzyme responsible for converting ingested galactose to glucose.Galactose-1-phosphate uridylyltransferase catalyzes the second step of the Leloir pathway of galactose metabolism, namely:The expression of GALT is controlled by the actions of the...
and identified the cause of the human metabolic disease galactosemia
Galactosemia
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...
as a defect in this enzyme.