Biochemistry, orbiological chemistry, is the study ofchemical processes within and relating to livingorganisms.[1] A sub-discipline of bothchemistry andbiology, biochemistry may be divided into three fields:structural biology,enzymology, andmetabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost allareas of the life sciences are being uncovered and developed through biochemical methodology and research.[2] Biochemistry focuses on understanding the chemical basis that allowsbiological molecules to give rise to the processes that occur within livingcells and between cells,[3] in turn relating greatly to the understanding oftissues andorgans as well as organism structure and function.[4] Biochemistry is closely related tomolecular biology, the study of themolecular mechanisms of biological phenomena.[5]
At its most comprehensive definition, biochemistry can be seen as a study of the components and composition of living things and how they come together to become life. In this sense, the history of biochemistry may therefore go back as far as theancient Greeks.[10] However, biochemistry as a specificscientific discipline began sometime in the 19th century, or a little earlier, depending on which aspect of biochemistry is being focused on. Some argued that the beginning of biochemistry may have been the discovery of the firstenzyme,diastase (now calledamylase), in 1833 byAnselme Payen,[11] while others consideredEduard Buchner's first demonstration of a complex biochemical processalcoholic fermentation in cell-free extracts in 1897 to be the birth of biochemistry.[12][13] Some might also point as its beginning to the influential 1842 work byJustus von Liebig,Animal chemistry, or,Organic chemistry in its applications tophysiology andpathology, which presented a chemical theory of metabolism,[10] or even earlier to the 18th century studies onfermentation andrespiration byAntoine Lavoisier.[14][15] Many other pioneers in the field who helped to uncover the layers of complexity of biochemistry have been proclaimed founders of modern biochemistry.Emil Fischer, who studied the chemistry ofproteins,[16] andF. Gowland Hopkins, who studiedenzymes and the dynamic nature of biochemistry, represent two examples of early biochemists.[17]
The term "biochemistry" was first used when Vinzenz Kletzinsky (1826–1882) had his "Compendium der Biochemie" printed in Vienna in 1858; it derived from a combination ofbiology andchemistry. In 1877,Felix Hoppe-Seyler used the term (biochemie in German) as a synonym forphysiological chemistry in the foreword to the first issue ofZeitschrift für Physiologische Chemie (Journal of Physiological Chemistry) where he argued for the setting up of institutes dedicated to this field of study.[18][19] The GermanchemistCarl Neuberg however is often cited to have coined the word in 1903,[20][21][22] while some credited it toFranz Hofmeister.[23]
Around two dozenchemical elements are essential to various kinds ofbiological life. Most rare elements on Earth are not needed by life (exceptions beingselenium andiodine),[33] while a few common ones (aluminium andtitanium) are not used. Most organisms share element needs, but there are a few differences betweenplants andanimals. For example, ocean algae usebromine, but land plants and animals do not seem to need any. All animals requiresodium, but is not an essential element for plants. Plants needboron andsilicon, but animals may not (or may need ultra-small amounts).[34]
Just six elements—carbon,hydrogen,nitrogen,oxygen,calcium andphosphorus—make up almost 99% of the mass of living cells, including those in the human body (seecomposition of the human body for a complete list). In addition to the six major elements that compose most of the human body, humans require smaller amounts of possibly 18 more.[35]
Two of the main functions of carbohydrates are energy storage and providing structure. One of the commonsugars known asglucose is a carbohydrate, but not all carbohydrates are sugars. There are more carbohydrates on Earth than any other known type of biomolecule; they are used to store energy andgenetic information, as well as play important roles in cell tocell interactions andcommunications.[citation needed]
The simplest type of carbohydrate is amonosaccharide, which among other properties containscarbon,hydrogen, andoxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOn, wheren is at least 3).Glucose (C6H12O6) is one of the most important carbohydrates; others includefructose (C6H12O6), the sugar commonly associated with thesweet taste offruits,[37][a] anddeoxyribose (C5H10O4), a component ofDNA. A monosaccharide can switch betweenacyclic (open-chain) form and acyclic form. The open-chain form can be turned into a ring of carbon atoms bridged by anoxygen atom created from thecarbonyl group of one end and thehydroxyl group of another. The cyclic molecule has ahemiacetal orhemiketal group, depending on whether the linear form was analdose or aketose.[39]
In these cyclic forms, the ring usually has5 or6 atoms. These forms are calledfuranoses andpyranoses, respectively—by analogy withfuran andpyran, the simplest compounds with the same carbon-oxygen ring (although they lack the carbon-carbondouble bonds of these two molecules). For example, the aldohexoseglucose may form a hemiacetal linkage between the hydroxyl on carbon 1 and the oxygen on carbon 4, yielding a molecule with a 5-membered ring, calledglucofuranose. The same reaction can take place between carbons 1 and 5 to form a molecule with a 6-membered ring, calledglucopyranose. Cyclic forms with a 7-atom ring calledheptoses are rare.[citation needed]
Two monosaccharides can be joined by aglycosidic orester bond into adisaccharide through adehydration reaction during which a molecule of water is released. The reverse reaction in which the glycosidic bond of a disaccharide is broken into two monosaccharides is termedhydrolysis. The best-known disaccharide issucrose or ordinarysugar, which consists of aglucose molecule and afructose molecule joined. Another important disaccharide islactose found in milk, consisting of a glucose molecule and agalactose molecule. Lactose may be hydrolysed bylactase, and deficiency in this enzyme results inlactose intolerance.
When a few (around three to six) monosaccharides are joined, it is called anoligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers andsignals, as well as having some other uses.[40] Many monosaccharides joined form apolysaccharide. They can be joined in one long linear chain, or they may bebranched. Two of the most common polysaccharides arecellulose andglycogen, both consisting of repeating glucosemonomers.Cellulose is an important structural component of plant'scell walls andglycogen is used as a form of energy storage in animals.
Sugar can be characterized by havingreducing or non-reducing ends. Areducing end of a carbohydrate is a carbon atom that can be in equilibrium with the open-chainaldehyde (aldose) or keto form (ketose). If the joining of monomers takes place at such a carbon atom, the freehydroxy group of thepyranose orfuranose form is exchanged with an OH-side-chain of another sugar, yielding a fullacetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety forms a full acetal with the C4-OH group of glucose.Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).
Lipids comprise a diverse range ofmolecules and to some extent is a catchall for relatively water-insoluble ornonpolar compounds of biological origin, includingwaxes,fatty acids, fatty-acid derivedphospholipids,sphingolipids,glycolipids, andterpenoids (e.g.,retinoids andsteroids). Some lipids are linear, open-chainaliphatic molecules, while others have ring structures. Some arearomatic (with a cyclic [ring] and planar [flat] structure) while others are not. Some are flexible, while others are rigid.[43]
Lipids are usually made from one molecule ofglycerol combined with other molecules. Intriglycerides, the main group of bulk lipids, there is one molecule of glycerol and threefatty acids. Fatty acids are considered the monomer in that case, and may besaturated (nodouble bonds in the carbon chain) or unsaturated (one or more double bonds in the carbon chain).[citation needed]
Most lipids have somepolar character and are largely nonpolar. In general, the bulk of their structure is nonpolar orhydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents likewater. Another part of their structure is polar orhydrophilic ("water-loving") and will tend to associate with polar solvents like water. This makes themamphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case ofcholesterol, the polar group is a mere –OH (hydroxyl or alcohol).[44]
In the case of phospholipids, the polar groups are considerably larger and more polar, as described below.
Lipids are an integral part of our daily diet. Mostoils andmilk products that we use for cooking and eating likebutter,cheese,ghee etc. are composed offats.Vegetable oils are rich in variouspolyunsaturated fatty acids (PUFA). Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, the final degradation products of fats and lipids. Lipids, especiallyphospholipids, are also used in variouspharmaceutical products, either as co-solubilizers (e.g. in parenteral infusions) or else asdrug carrier components (e.g. in aliposome ortransfersome).
The general structure of an α-amino acid, with theamino group on the left and thecarboxyl group on the right
Proteins are very large molecules—macro-biopolymers—made from monomers calledamino acids. An amino acid consists of an alpha carbon atom attached to anamino group, –NH2, acarboxylic acid group, –COOH (although these exist as –NH3+ and –COO− under physiologic conditions), a simplehydrogen atom, and a side chain commonly denoted as "–R". The side chain "R" is different for each amino acid of which there are 20standard ones. It is this "R" group that makes each amino acid different, and the properties of the side chains greatly influence the overallthree-dimensional conformation of a protein. Some amino acids have functions by themselves or in a modified form; for instance,glutamate functions as an importantneurotransmitter. Amino acids can be joined via apeptide bond. In thisdehydration synthesis, awater molecule is removed and the peptide bond connects thenitrogen of one amino acid's amino group to the carbon of the other's carboxylic acid group. The resulting molecule is called adipeptide, and short stretches of amino acids (usually, fewer than thirty) are calledpeptides orpolypeptides. Longer stretches merit the titleproteins. As an example, the important bloodserum proteinalbumin contains 585amino acid residues.[45]
Generic amino acids (1) in neutral form, (2) as they exist physiologically, and (3) joined as a dipeptideA schematic ofhemoglobin. The red and blue ribbons represent the proteinglobin; the green structures are theheme groups.
Proteins can have structural and/or functional roles. For instance, movements of the proteinsactin andmyosin ultimately are responsible for the contraction of skeletal muscle. One property many proteins have is that they specifically bind to a certain molecule or class of molecules—they may beextremely selective in what they bind.Antibodies are an example of proteins that attach to one specific type of molecule. Antibodies are composed of heavy and light chains. Two heavy chains would be linked to two light chains throughdisulfide linkages between their amino acids. Antibodies are specific through variation based on differences in the N-terminal domain.[46]
Theenzyme-linked immunosorbent assay (ELISA), which uses antibodies, is one of the most sensitive tests modern medicine uses to detect various biomolecules. Probably the most important proteins, however, are theenzymes. Virtually every reaction in a living cell requires an enzyme to lower theactivation energy of the reaction. These molecules recognize specific reactant molecules calledsubstrates; they thencatalyze the reaction between them. By lowering theactivation energy, the enzyme speeds up that reaction by a rate of 1011 or more; a reaction that would normally take over 3,000 years to complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the process and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole.
The structure of proteins is traditionally described in a hierarchy of four levels. Theprimary structure of a protein consists of its linear sequence of amino acids; for instance, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-...".Secondary structure is concerned with local morphology (morphology being the study of structure). Some combinations of amino acids will tend to curl up in a coil called anα-helix or into a sheet called aβ-sheet; some α-helixes can be seen in the hemoglobin schematic above.Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin contains 146 amino acid residues; substitution of theglutamate residue at position 6 with avaline residue changes the behavior of hemoglobin so much that it results insickle-cell disease. Finally,quaternary structure is concerned with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins have more than one subunit.[47]
Examples of protein structures from theProtein Data BankMembers of a protein family, as represented by the structures of theisomerasedomains
Ingested proteins are usually broken up into single amino acids or dipeptides in thesmall intestine and then absorbed. They can then be joined to form new proteins. Intermediate products of glycolysis, the citric acid cycle, and thepentose phosphate pathway can be used to form all twenty amino acids, and most bacteria and plants possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can synthesize only half of them. They cannot synthesizeisoleucine,leucine,lysine,methionine,phenylalanine,threonine,tryptophan, andvaline. Because they must be ingested, these are theessential amino acids. Mammals do possess the enzymes to synthesizealanine,asparagine,aspartate,cysteine,glutamate,glutamine,glycine,proline,serine, andtyrosine, the nonessential amino acids. While they can synthesizearginine andhistidine, they cannot produce it in sufficient amounts for young, growing animals, and so these are often considered essential amino acids.
If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid. Enzymes calledtransaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an amino group is added, often viatransamination. The amino acids may then be linked together to form a protein.
A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Freeammonia (NH3), existing as theammonium ion (NH4+) in blood, is toxic to life forms. A suitable method for excreting it must therefore exist. Different tactics have evolved in different animals, depending on the animals' needs.Unicellular organisms release the ammonia into the environment. Likewise,bony fish can release ammonia into the water where it is quickly diluted. In general, mammals convert ammonia into urea, via theurea cycle.
In order to determine whether two proteins are related, or in other words to decide whether they are homologous or not, scientists use sequence-comparison methods. Methods likesequence alignments andstructural alignments are powerful tools that help scientists identifyhomologies between related molecules. The relevance of finding homologies among proteins goes beyond forming an evolutionary pattern ofprotein families. By finding how similar two protein sequences are, we acquire knowledge about their structure and therefore their function.
The structure ofdeoxyribonucleic acid (DNA); the picture shows the monomers being put together.
Nucleic acids, so-called because of their prevalence in cellularnuclei, is the generic name of the family ofbiopolymers. They are complex, high-molecular-weight biochemical macromolecules that can conveygenetic information in all living cells and viruses.[2] The monomers are callednucleotides, and each consists of three components: a nitrogenous heterocyclicbase (either apurine or apyrimidine), a pentose sugar, and aphosphate group.[48]
Structural elements of common nucleic acid constituents. Because they contain at least one phosphate group, the compounds markednucleoside monophosphate,nucleoside diphosphate andnucleoside triphosphate are all nucleotides (not phosphate-lackingnucleosides).
The most common nucleic acids aredeoxyribonucleic acid (DNA) andribonucleic acid (RNA). Thephosphate group and the sugar of each nucleotide bond with each other to form the backbone of the nucleic acid, while the sequence of nitrogenous bases stores the information. The most common nitrogenous bases areadenine,cytosine,guanine,thymine, anduracil. Thenitrogenous bases of each strand of a nucleic acid will formhydrogen bonds with certain other nitrogenous bases in a complementary strand of nucleic acid. Adenine binds with thymine and uracil, thymine binds only with adenine, and cytosine and guanine can bind only with one another. Adenine, thymine, and uracil contain two hydrogen bonds, while hydrogen bonds formed between cytosine and guanine are three.
Aside from the genetic material of the cell, nucleic acids often play a role assecond messengers, as well as forming the base molecule foradenosine triphosphate (ATP), the primary energy-carrier molecule found in all living organisms. Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while thymine occurs only in DNA and uracil occurs in RNA.
Glucose is an energy source in most life forms. For instance, polysaccharides are broken down into their monomers byenzymes (glycogen phosphorylase removes glucose residues from glycogen, a polysaccharide). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides.[49]
Themetabolic pathway of glycolysis convertsglucose topyruvate via a series of intermediate metabolites. Each chemical modification is performed by a different enzyme. Steps 1 and 3 consumeATP and steps 7 and 10 produce ATP. Since steps 6–10 occur twice per glucose molecule, this leads to a net production of ATP.
Glucose is mainly metabolized by a very important ten-steppathway calledglycolysis, the net result of which is to break down one molecule of glucose into two molecules ofpyruvate. This also produces a net two molecules ofATP, the energy currency of cells, along with two reducing equivalents of convertingNAD+ (nicotinamide adenine dinucleotide: oxidized form) to NADH (nicotinamide adenine dinucleotide: reduced form). This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate tolactate (lactic acid) (e.g. in humans) or toethanol plus carbon dioxide (e.g. inyeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway.[50]
Inaerobic cells with sufficientoxygen, as in most human cells, the pyruvate is further metabolized. It is irreversibly converted toacetyl-CoA, giving off one carbon atom as the waste productcarbon dioxide, generating another reducing equivalent asNADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter thecitric acid cycle, producing two molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (viaFADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, anelectron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thus, oxygen is reduced to water and the original electron acceptors NAD+ andquinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle).[51] It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of oxygen.
Invertebrates, vigorously contractingskeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift toanaerobic metabolism, converting glucose to lactate.The combination of glucose from noncarbohydrates origin, such as fat and proteins. This only happens whenglycogen supplies in the liver are worn out. The pathway is a crucial reversal ofglycolysis from pyruvate to glucose and can use many sources like amino acids, glycerol andKrebs Cycle. Large scale protein and fatcatabolism usually occur when those suffer from starvation or certain endocrine disorders.[52] Theliver regenerates the glucose, using a process calledgluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (orstarch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides. The combined pathways of glycolysis during exercise, lactate's crossing via the bloodstream to the liver, subsequent gluconeogenesis and release of glucose into the bloodstream is called theCori cycle.[53]
Relationship to other "molecular-scale" biological sciences
Researchers in biochemistry use specific techniques native to biochemistry, but increasingly combine these with techniques and ideas developed in the fields ofgenetics,molecular biology, andbiophysics. There is not a defined line between these disciplines. Biochemistry studies thechemistry required for biological activity of molecules, molecular biology studies their biological activity,genetics studies their heredity, which happens to be carried by theirgenome. This is shown in the following schematic that depicts one possible view of the relationships between the fields:
Biochemistry is the study of the chemical substances and vital processes occurring in liveorganisms.Biochemists focus heavily on the role, function, and structure ofbiomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are applications of biochemistry. Biochemistry studies life at the atomic and molecular level.
Genetics is the study of the effect of genetic differences in organisms. This can often be inferred by the absence of a normal component (e.g. onegene). The study of "mutants" – organisms that lack one or more functional components with respect to the so-called "wild type" or normalphenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knockout" studies.
Molecular biology is the study of molecular underpinnings of the biological phenomena, focusing on molecular synthesis, modification, mechanisms and interactions. Thecentral dogma of molecular biology, where genetic material is transcribed into RNA and then translated intoprotein, despite being oversimplified, still provides a good starting point for understanding the field. This concept has been revised in light of emerging novel roles forRNA.
Chemical biology seeks to develop new tools based onsmall molecules that allow minimal perturbation of biological systems while providing detailed information about their function. Further, chemical biology employs biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example emptiedviral capsids that can delivergene therapy ordrug molecules).
^Fructose is not the only sugar found in fruits. Glucose and sucrose are also found in varying quantities in various fruits, and sometimes exceed the fructose present. For example, 32% of the edible portion of adate is glucose, compared with 24% fructose and 8% sucrose. However,peaches contain more sucrose (6.66%) than they do fructose (0.93%) or glucose (1.47%).[38]
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Kauffman, George B.; Chooljian, Steven H. (2001). "Friedrich Wöhler (1800–1882), on the Bicentennial of His Birth".The Chemical Educator.6 (2):121–133.doi:10.1007/s00897010444a.S2CID93425404.
Nielsen, Forrest H. (1999). "Ultratrace minerals". In Maurice E. Shils; et al. (eds.).Modern Nutrition in Health and Disease. Baltimore: Williams & Wilkins. pp. 283–303.hdl:10113/46493.
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