History of biochemistry

The history of biochemistry spans approximately 400 years. Although the term “biochemistry” seems to have been first used in 1882, it is generally accepted that the word "biochemistry" was first proposed in 1903 by Carl Neuberg, a German chemist.

Vitalism and urea

Originally, it was generally believed that life was not subject to the laws of science the way non-life was. It was thought that only living beings could produce the molecules of life (from other, previously existing biomolecules). Then, in 1828, Friedrich Wöhler published a paper about the synthesis of urea, proving that organic compounds can be created artificially.

Enzymes

Eduard Buchner

As early as the late 1700s and early 1800s, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were known. However, the mechanism by which this occurred had not been identified.

In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms. He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."

In 1878 German physiologist Wilhelm Kühne (1837–1900) coined the term enzyme, which comes from Greek ενζυμον "in leaven", to describe this process. The word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment used to refer to chemical activity produced by living organisms.

In 1897 Eduard Buchner began to study the ability of yeast extracts to ferment sugar despite the absence of living yeast cells. In a series of experiments at the University of Berlin, he found that the sugar was fermented even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose "zymase". In 1907 he received the Nobel Prize in Chemistry "for his biochemical research and his discovery of cell-free fermentation". Following Buchner's example; enzymes are usually named according to the reaction they carry out. Typically the suffix -ase is added to the name of the substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of reaction (e.g., DNA polymerase forms DNA polymers).

Having shown that enzymes could function outside a living cell, the next step was to determine their biochemical nature. Many early workers noted that enzymatic activity was associated with proteins, but several scientists (such as Nobel laureate Richard Willstätter) argued that proteins were merely carriers for the true enzymes and that proteins per se were incapable of catalysis. However, in 1926, James B. Sumner showed that the enzyme urease was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop and Stanley, who worked on the digestive enzymes pepsin (1930), trypsin and chymotrypsin. These three scientists were awarded the 1946 Nobel Prize in Chemistry.

This discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This was first done for lysozyme, an enzyme found in tears, saliva and egg whites that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail.

Metabolism

Santorio Santorio in his steelyard balance, from Ars de statica medecina, first published 1614

The term metabolism is derived from the Greek Μεταβολισμός – Metabolismos for "change", or "overthrow". The history of the scientific study of metabolism spans 400 years. The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medecina. This book describes how he weighed himself before and after eating, sleeping, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called "insensible perspiration".

20th century

Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle). One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.

Today, the findings of biochemistry are used in many areas, from genetics to molecular biology and from agriculture to medicine.

See also

• History of biology
• History of chemistry
• History of molecular biology

Further reading

• Fruton, Joseph S. Proteins, Enzymes, Genes: The Interplay of Chemistry and Biology. Yale University Press: New Haven, 1999. ISBN 0-300-07608-8
• Kohler, Robert. From Medical Chemistry to Biochemistry: The Making of a Biomedical Discipline. Cambridge University Press, 1982.