The history of biochemistry can be said to have started with the ancient Greeks who were interested in the composition and processes of life, although

biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

as a specific scientific discipline has its beginning around the early 19th century. Some argued that the beginning of biochemistry may have been the discovery of the first

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

diastase A diastase (; from Greek διάστασις, "separation") is any one of a group of enzymes that catalyses the breakdown of starch into maltose. Alpha amylase degrades starch to a mixture of the disaccharide maltose; the trisaccharide maltotriose, ...

(today called

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

), in 1833 by

Anselme Payen Anselme Payen (; 6 January 1795 – 12 May 1871) was a French chemist known for discovering the enzyme diastase, and the carbohydrate cellulose. Biography Payen was born in Paris. He began studying science with his father when he was a 13-yea ...

, while others considered

Eduard Buchner Eduard Buchner (; 20 May 1860 – 13 August 1917) was a German chemist and zymologist, awarded the 1907 Nobel Prize in Chemistry for his work on fermentation. Biography Early years Buchner was born in Munich to a physician and Doctor Extraor ...

's first demonstration of a complex biochemical process

alcoholic fermentation Ethanol fermentation, also called alcoholic fermentation, is a biological process which converts sugars such as glucose, fructose, and sucrose into cellular energy, producing ethanol and carbon dioxide as by-products. Because yeasts perform this ...

in cell-free extracts to be the birth of biochemistry. Some might also point to the influential work of Justus von Liebig from 1842, ''Animal chemistry, or, Organic chemistry in its applications to physiology and pathology'', which presented a chemical theory of metabolism, or even earlier to the 18th century studies on fermentation and respiration by

Antoine Lavoisier Antoine-Laurent de Lavoisier ( , ; ; 26 August 17438 May 1794),
CNRS (

'' itself is derived from the combining form ''bio-'', meaning 'life', and '' chemistry''. The word is first recorded in English in 1848, while in 1877,

Felix Hoppe-Seyler Ernst Felix Immanuel Hoppe-Seyler (''né'' Felix Hoppe; 26 December 1825 – 10 August 1895) was a German physiologist and chemist, and the principal founder of the disciplines of biochemistry and molecular biology. Biography Hoppe-Seyler was b ...

used the term ( in German) in the foreword to the first issue of '' Zeitschrift für Physiologische Chemie'' (Journal of Physiological Chemistry) as a synonym for

physiological chemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology a ...

and argued for the setting up of institutes dedicate to its studies. Nevertheless, several sources cite German

chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe t ...

Carl Neuberg Carl Alexander Neuberg (29 July 1877 – 30 May 1956) was an early pioneer in biochemistry, and he is often referred to as the "father of modern biochemistry". His notable contribution to science includes the discovery of the carboxylase and the ...

as having coined the term for the new discipline in 1903, and some credit it to Franz Hofmeister. The subject of study in biochemistry is the chemical processes in living organisms, and its history involves the discovery and understanding of the complex components of life and the elucidation of pathways of biochemical processes. Much of biochemistry deals with the structures and functions of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules; their metabolic pathways and flow of chemical energy through metabolism; how biological molecules give rise to the processes that occur within living cells; it also focuses on the biochemical processes involved in the control of information flow through biochemical signalling, and how they relate to the functioning of whole organisms. Over the last 40 years the field has had success in explaining living processes such that now almost all areas of the life sciences from botany to medicine are engaged in biochemical research. 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 twenty or more amino acids, carbohydrates are formed from sugars known as monosaccharides, oligosaccharides, and polysaccharides, lipids are formed from fatty acids and glycerols, and nucleic acids are formed from nucleotides. 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 The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

(DNA, RNA), protein synthesis,

cell membrane transport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

, and signal transduction.

Proto-biochemistry

In a sense, the study of biochemistry can be considered to have started in ancient times, for example when

biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

first began to interest society—as the ancient Chinese developed a system of medicine based on

yin and yang Yin and yang ( and ) is a Chinese philosophical concept that describes opposite but interconnected forces. In Chinese cosmology, the universe creates itself out of a primary chaos of material energy, organized into the cycles of yin and ya ...

, and also the

five phases (; Japanese: (); Korean: (); Vietnamese: ''ngũ hành'' (五行)), usually translated as Five Phases or Five Agents, is a fivefold conceptual scheme that many traditional Chinese fields used to explain a wide array of phenomena, from cosmi ...

, which both resulted from alchemical and biological interests. Its beginning in the ancient Indian culture was linked to an interest in medicine, as they developed the concept of three humors that were similar to the Greeks' four humours (see

humorism Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek and Roman physicians and philosophers. Humorism began to fall out of favor in the 1850s ...

). They also delved into the interest of bodies being composed of tissues. The ancient Greeks' conception of biochemistry was linked with their ideas on matter and disease, where good health was thought to come from a balance of the

four elements Classical elements typically refer to earth, water, air, fire, and (later) aether which were proposed to explain the nature and complexity of all matter in terms of simpler substances. Ancient cultures in Greece, Tibet, and India had simi ...

and

four humors Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek and Roman physicians and philosophers. Humorism began to fall out of favor in the 1850s ...

in the human body. As in the majority of early sciences, the Islamic world contributed significantly to early biological advancements as well as alchemical advancements; especially with the introduction of clinical trials and

clinical pharmacology Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinic ...

presented in Avicenna's ''

The Canon of Medicine ''The Canon of Medicine'' ( ar, القانون في الطب, italic=yes ''al-Qānūn fī al-Ṭibb''; fa, قانون در طب, italic=yes, ''Qanun-e dâr Tâb'') is an encyclopedia of medicine in five books compiled by Persian physician-phi ...

''. On the side of chemistry, early advancements were heavily attributed to exploration of alchemical interests but also included: metallurgy,

the scientific method ''The'' () is a grammatical Article (grammar), article in English language, English, denoting persons or things already mentioned, under discussion, implied or otherwise presumed familiar to listeners, readers, or speakers. It is the definite ...

, and early theories of

atomism Atomism (from Greek , ''atomon'', i.e. "uncuttable, indivisible") is a natural philosophy proposing that the physical universe is composed of fundamental indivisible components known as atoms. References to the concept of atomism and its atoms ...

. In more recent times, the study of chemistry was marked by milestones such as the development of Mendeleev's periodic table, Dalton's

atomic model Atomic theory is the scientific theory that matter is composed of particles called atoms. Atomic theory traces its origins to an ancient philosophical tradition known as atomism. According to this idea, if one were to take a lump of matter an ...

, and the

conservation of mass In physics and chemistry, the law of conservation of mass or principle of mass conservation states that for any system closed to all transfers of matter and energy, the mass of the system must remain constant over time, as the system's mass can ...

theory. This last mention has the most importance of the three due to the fact that this law intertwines chemistry with

thermodynamics Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of th ...

in an intercalated manner.

Enzymes

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 Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

, Louis Pasteur concluded that this fermentation was catalyzed by a vital force contained within the yeast cells called '' ferments'', which he thought functioned 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 1833

discovered the first

, and in 1878 German physiologist

Wilhelm Kühne Wilhelm Friedrich Kühne (28 March 183710 June 1900) was a German physiologist. Born in Hamburg, he is best known today for coining the word enzyme in 1878. Biography Kühne was born at Hamburg on 28 March 1837. After attending the gymnasium ...

(1837–1900) coined the term ''

'', which comes from

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

'in leaven', to describe this process. The word ''enzyme'' was used later to refer to nonliving substances such as

pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, w ...

, and the word ''ferment'' was used to refer to chemical activity produced by living organisms. In 1897

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-Universität zu Berlin (german: Humboldt-Universität zu Berlin, abbreviated HU Berlin) is a German public research university in the central borough of Mitte in Berlin. It was established by Frederick William III on the initiative ...

, 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 is an enzyme complex that catalyzes the fermentation of sugar into ethanol and carbon dioxide. It occurs naturally in yeasts. Zymase activity varies among yeast strains. Zymase is also the brand name of the drug pancrelipase. Cell-free ...

''. In 1907 he received the

Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...

"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 Lactase is an enzyme produced by many organisms. It is located in the brush border of the small intestine of humans and other mammals. Lactase is essential to the complete digestion of whole milk; it breaks down lactose, a sugar which gives ...

is the enzyme that cleaves lactose) or the type of reaction (''e.g.'',

DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...

forms DNA polymers). 1QPS

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 Martin Willstätter FRS(For) HFRSE (, 13 August 1872 – 3 August 1942) was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invente ...

) 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 Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-contai ...

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 Stanley may refer to: Arts and entertainment Film and television * ''Stanley'' (1972 film), an American horror film * ''Stanley'' (1984 film), an Australian comedy * ''Stanley'' (1999 film), an animated short * ''Stanley'' (1956 TV series) ...

, 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, meant that scientists eventually could solve their structures by

x-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

. This was first done for

lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

, 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 Structural biology is a field that is many centuries old which, and as defined by the Journal of Structural Biology, deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every le ...

and the effort to understand how enzymes work at an atomic level of detail.

Metabolism

Early metabolic interest

The term ''metabolism'' is derived from the

– for 'change', or 'overthrow'. The history of the scientific study of metabolism spans 800 years. The earliest of all metabolic studies began during the early thirteenth century (1213–1288) by a Muslim scholar from Damascus named Ibn al-Nafis. al-Nafis stated in his most well-known work ''Theologus Autodidactus'' that "that body and all its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change." Although al-Nafis was the first documented physician to have an interest in biochemical concepts, the first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book . 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".

Metabolism: 20th century – present

One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. Krebs was a student of extremely important Otto Warburg, and wrote a biography of Warburg by that title in which he presents Warburg as being educated to do for biological chemistry what Fischer did for organic chemistry. Which he did. Krebs discovered the urea cycle and later, working with

Hans Kornberg Sir Hans Leo Kornberg, FRS (14 January 1928 – 16 December 2019) was a British-American biochemist. He was Sir William Dunn Professor of Biochemistry in the University of Cambridge from 1975 to 1995, and Master of Christ's College, Cambridge ...

, the citric acid cycle and the glyoxylate cycle. These discoveries led to Krebs being awarded the

Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

in physiology in 1953, which was shared with the German biochemist

Fritz Albert Lipmann Fritz Albert Lipmann (; June 12, 1899 – July 24, 1986) 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 the Nobel Prize in Physiology or Medicine in ...

who also codiscovered the essential cofactor coenzyme A.

Glucose absorption

In 1960, the biochemist Robert K. Crane revealed his discovery of the sodium-glucose

cotransport In Cellular Biology, cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane Second law of thermodynamics, from a region of lower concentration to a region of higher concentration—against the concentra ...

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. This discovery, however, would not have been possible if it were not for the discovery of the molecule

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

's structure and chemical makeup. These discoveries are largely attributed to the German chemist

Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of draw ...

who received the

in chemistry nearly 60 years earlier.

Glycolysis

Since metabolism focuses on the breaking down (catabolic processes) of molecules and the building of larger molecules from these particles (anabolic processes), the use of glucose and its involvement in the formation of

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms o ...

(ATP) is fundamental to this understanding. The most frequent type of glycolysis found in the body is the type that follows the Embden-Meyerhof-Parnas (EMP) Pathway, which was discovered by

Gustav Embden Gustav Georg Embden (10 November 1874 – 25 July 1933) was a German physiological chemist. Background Gustav Embden was a son of the Hamburg lawyer and politician George Heinrich Embden. His grandmother Charlotte Heine was a well-known salonn ...

Otto Meyerhof Otto Fritz Meyerhof (; April 12, 1884 – October 6, 1951) was a German physician and biochemist who won the 1922 Nobel Prize in Physiology and Medicine. Biography Otto Fritz Meyerhof was born in Hannover, at Theaterplatz 16A (now:Rathenaustrasse ...

, and Jakob Karol Parnas. These three men discovered that glycolysis is a strongly determinant process for the efficiency and production of the human body. The significance of the pathway shown in the adjacent image is that by identifying the individual steps in this process doctors and researchers are able to pinpoint sites of metabolic malfunctions such as

pyruvate kinase deficiency Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and ...

that can lead to severe anemia. This is most important because cells, and therefore organisms, are not capable of surviving without proper functioning metabolic pathways.

Instrumental advancements (20th century)

Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system ( ...

, X-ray diffraction,

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...

, radioisotopic labelling, electron microscopy and

molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of t ...

simulations. These techniques allowed for the discovery and detailed analysis of many molecules and

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

s of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

, such as glycolysis and the

Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

(citric acid cycle). The example of an NMR instrument shows that some of these instruments, such as the HWB-NMR, can be very large in size and can cost anywhere from a few thousand dollars to millions of dollars ($16 million for the one shown here).

Polymerase chain reaction

Polymerase chain reaction (PCR) is the primary gene amplification technique that has revolutionized modern biochemistry. Polymerase chain reaction was developed by Kary Mullis in 1983. There are four steps to a proper polymerase chain reaction: 1) denaturation 2) extension 3) insertion (of gene to be expressed) and finally 4) amplification of the inserted gene. These steps with simple illustrative examples of this process can be seen in the image below and to the right of this section. This technique allows for the copy of a single gene to be amplified into hundreds or even millions of copies and has become a cornerstone in the protocol for any biochemist that wishes to work with bacteria and gene expression. PCR is not only used for gene expression research but is also capable of aiding laboratories in diagnosing certain diseases such a

lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

, some types of

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

, and other

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

diseases that can sometimes puzzle doctors. Without polymerase chain reaction development, there are many advancements in the field of bacterial study and protein expression study that would not have come to fruition. The development of the theory and process of

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...

is essential but the invention of the

thermal cycler The thermal cycler (also known as a thermocycler, PCR machine or DNA amplifier) is a laboratory apparatus most commonly used to amplify segments of DNA via the polymerase chain reaction (PCR). Thermal cyclers may also be used in laboratories to fa ...

is equally as important because the process would not be possible without this instrument. This is yet another testament to the fact that the advancement of technology is just as crucial to sciences such as biochemistry as is the painstaking research that leads to the development of theoretical concepts.