History of biochemistry
Encyclopedia
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
.
Biochemistry is the study of chemical processes in living organisms. Biochemistry governs all living organisms and living processes. By controlling information flow through biochemical signalling and the flow of chemical energy through metabolism, biochemical processes give rise to the incredible complexity of life. Much of biochemistry deals with the structures and functions of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules although increasingly processes rather than individual molecules are the main focus. Over the last 40 years biochemistry has become so successful at explaining living processes that now almost all areas of the life sciences from botany to medicine are engaged in biochemical research. Today the main focus of pure biochemistry is in understanding how biological molecules give rise to the processes that occur within living cells which in turn relates greatly to the study and understanding of whole organisms.
Among the vast number of different biomolecules, many are complex and large molecules (called polymers), which are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types. For example, a protein is a polymer whose subunits are selected from a set of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, and in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction.
As early as the late 18th century and early 19th century, 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 white
s 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.
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".
, 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 pathway
s 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.
In 1960, the biochemist Robert K. Crane
revealed his discovery of the sodium-glucose cotransport
as the mechanism for intestinal glucose absorption. This was the very first proposal of a coupling between the fluxes of an ion and a substrate that has been seen as sparking a revolution in biology.
Today, the findings of biochemistry are used in many areas, from genetics
to molecular biology
and from agriculture to medicine
.
Carl Neuberg
Carl Alexander Neuberg was an early pioneer in biochemistry, and often referred to as the "Father of Biochemistry".He was the first editor of the journal Biochemische Zeitschrift. This journal was founded in 1906 and is now known as the FEBS Journal. Neuberg was born in Hanover, Germany and...
, a German chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
.
Biochemistry is the study of chemical processes in living organisms. Biochemistry governs all living organisms and living processes. By controlling information flow through biochemical signalling and the flow of chemical energy through metabolism, biochemical processes give rise to the incredible complexity of life. Much of biochemistry deals with the structures and functions of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules although increasingly processes rather than individual molecules are the main focus. Over the last 40 years biochemistry has become so successful at explaining living processes that now almost all areas of the life sciences from botany to medicine are engaged in biochemical research. Today the main focus of pure biochemistry is in understanding how biological molecules give rise to the processes that occur within living cells which in turn relates greatly to the study and understanding of whole organisms.
Among the vast number of different biomolecules, many are complex and large molecules (called polymers), which are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types. For example, a protein is a polymer whose subunits are selected from a set of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, and in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction.
Enzymes
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
to sugars by plant extracts and saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
were known. However, the mechanism by which this occurred had not been identified.
In the 19th century, when studying the fermentation
Fermentation (food)
Fermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...
of sugar to alcohol by yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
came to the conclusion that this fermentation was catalyzed by a vital force contained within the yeast cells called "ferments
Vitalism
Vitalism, as defined by the Merriam-Webster dictionary, is#a doctrine that the functions of a living organism are due to a vital principle distinct from biochemical reactions...
", 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
Wilhelm Kühne
Wilhelm Friedrich Kühne was a German physiologist. Born in Hamburg, he is best known today for coining the word enzyme.-Biography:...
(1837–1900) coined the term enzyme, which comes from Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
ενζυμον "in leaven", to describe this process. The word enzyme was used later to refer to nonliving substances such as pepsin
Pepsin
Pepsin is an enzyme whose precursor form is released by the chief cells in the stomach and that degrades food proteins into peptides. It was discovered in 1836 by Theodor Schwann who also coined its name from the Greek word pepsis, meaning digestion...
, and the word ferment used to refer to chemical activity produced by living organisms.
In 1897 Eduard Buchner
Eduard Buchner
Eduard Buchner was a German chemist and zymologist, awarded with the 1907 Nobel Prize in Chemistry thanks to his work on fermentation.-Early years:...
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
Humboldt University of Berlin
The Humboldt University of Berlin is Berlin's oldest university, founded in 1810 as the University of Berlin by the liberal Prussian educational reformer and linguist Wilhelm von Humboldt, whose university model has strongly influenced other European and Western universities...
, 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
Zymase
Zymase is an enzyme complex that catalyzes the fermentation of sugar into ethanol and carbon dioxide. They occur naturally in yeasts...
". In 1907 he received the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
"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
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
(e.g., lactase
Lactase
Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...
is the enzyme that cleaves lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
) or the type of reaction (e.g., DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
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
Richard Willstätter
Richard Martin Willstätter was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invented paper chromatography independently of Mikhail Tsvet.-Biography:Willstätter was born in to a Jewish family...
) 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
James B. Sumner
James Batcheller Sumner was an American chemist. He shared the Nobel Prize in Chemistry in 1946 with John Howard Northrop and Wendell Meredith Stanley.-Biography:...
showed that the enzyme urease
Urease
Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia. The reaction occurs as follows:In 1926, James Sumner showed that urease is a protein. Urease is found in bacteria, yeast, and several higher plants. The structure of urease was first solved by P.A...
was a pure protein and crystallized it; Sumner did likewise for the enzyme catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...
in 1937. The conclusion that pure proteins can be enzymes was definitively proved by Northrop
John Howard Northrop
John Howard Northrop was an American biochemist who won, with James Batcheller Sumner and Wendell Meredith Stanley, the 1946 Nobel Prize in Chemistry. The award was given for these scientists' isolation, crystallization, and study of enzymes, proteins, and viruses...
and Stanley
Wendell Meredith Stanley
Wendell Meredith Stanley was an American biochemist, virologist and Nobel laureate.-Biography:Stanley was born in Ridgeville, Indiana, and earned a BS in Chemistry at Earlham College in Richmond, Indiana. He then studied at the University of Illinois, gaining an MS in science in 1927 followed by...
, 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
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
. This was first done for lysozyme
Lysozyme
Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...
, an enzyme found in tears, saliva and egg white
Egg white
Egg white is the common name for the clear liquid contained within an egg. In chickens it is formed from the layers of secretions of the anterior section of the hen's oviduct during the passage of the egg. It forms around either fertilized or unfertilized egg yolks...
s that digests the coating of some bacteria; the structure was solved by a group led by David Chilton Phillips
David Chilton Phillips
David Chilton Phillips, Baron Phillips of Ellesmere, KBE, FRS is considered to be a founding father of the now expanding field of structural biology and was an influential figure in science and government...
and published in 1965. This high-resolution structure of lysozyme marked the beginning of the field of structural biology
Structural biology
Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function...
and the effort to understand how enzymes work at an atomic level of detail.
Metabolism
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
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 chromatographyChromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....
, X-ray diffraction, NMR spectroscopy
Protein nuclear magnetic resonance spectroscopy
Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins. The field was pioneered by Richard R. Ernst and Kurt Wüthrich, among others...
, radioisotopic labelling, electron microscopy
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
and molecular dynamics
Molecular dynamics
Molecular dynamics is a computer simulation of physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a period of time, giving a view of the motion of the atoms...
simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
s of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, such as glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
and the Krebs cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
(citric acid cycle). One of the most prolific of these modern biochemists was Hans Krebs
Hans Adolf Krebs
Sir Hans Adolf Krebs was a German-born British physician and biochemist. Krebs is best known for his identification of two important metabolic cycles: the urea cycle and the citric acid cycle...
who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg
Hans Kornberg
Professor Sir Hans Leo Kornberg, FRS is a British biochemist.-Early Life, Education and Career:Kornberg was born in 1928 in Germany of Jewish parents. In 1939 he left Nazi Germany , and moved to the care of an uncle in Yorkshire...
, the citric acid cycle and the glyoxylate cycle.
In 1960, the biochemist Robert K. Crane
Robert K. Crane
Robert Kellogg Crane is an American biochemist best known for his discovery of sodium-glucose cotransport.-Biography:...
revealed his discovery of the sodium-glucose cotransport
Co-transport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
as the mechanism for intestinal glucose absorption. This was the very first proposal of a coupling between the fluxes of an ion and a substrate that has been seen as sparking a revolution in biology.
Today, the findings of biochemistry are used in many areas, from genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
to molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
and from agriculture to medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
.
See also
- History of biologyHistory of biologyThe history of biology traces the study of the living world from ancient to modern times. Although the concept of biology as a single coherent field arose in the 19th century, the biological sciences emerged from traditions of medicine and natural history reaching back to ayurveda, ancient Egyptian...
- History of chemistryHistory of chemistryBy 1000 BC, ancient civilizations used technologies that would eventually form the basis of the various branches of chemistry. Examples include extracting metals from ores, making pottery and glazes, fermenting beer and wine, making pigments for cosmetics and painting, extracting chemicals from...
- History of molecular biologyHistory of molecular biologyThe history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological disciplines: biochemistry, genetics, microbiology, and virology...
- History of chromatographyHistory of chromatographyThe history of chromatography spans from the mid-19th century to the 21st. Chromatography, literally "color writing", was used—and named— in the first decade of the 20th century, primarily for the separation of plant pigments such as chlorophyll and carotenoids...
- History of RNA biologyHistory of RNA biologyNumerous key discoveries in biology have emerged from studies of RNA , including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that...
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.