Transferase
In biochemistry, a transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, and are integral to some of life's most important processes.
Transferases are involved in myriad reactions in the cell. Three examples of these reactions are the activity of coenzyme A transferase, which transfers thiol esters, the action of N-acetyltransferase, which is part of the pathway that metabolizes tryptophan, and the regulation of pyruvate dehydrogenase, which converts pyruvate to acetyl CoA. Transferases are also utilized during translation. In this case, an amino acid chain is the functional group transferred by a peptidyl transferase. The transfer involves the removal of the growing amino acid chain from the tRNA molecule in the A-site of the ribosome and its subsequent addition to the amino acid attached to the tRNA in the P-site.
Mechanistically, an enzyme that catalyzed the following reaction would be a transferase:
In the above reaction, X would be the donor, and Y would be the acceptor. R denotes the functional group transferred as a result of transferase activity. The donor is often a coenzyme.
History
Some of the most important discoveries relating to transferases occurred as early as the 1930s. Earliest discoveries of transferase activity occurred in other classifications of enzymes, including beta-galactosidase, protease, and acid/base phosphatase. Prior to the realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers.Image:Dopamine degradation.svg|thumb|right|Biodegradation of dopamine via catechol-O-methyltransferase. The mechanism for dopamine degradation led to the Nobel Prize in Physiology or Medicine in 1970.
Transamination, or the transfer of an amine group from an amino acid to a keto acid by an aminotransferase, was first noted in 1930 by Dorothy M. Needham, after observing the disappearance of glutamic acid added to pigeon breast muscle. This observance was later verified by the discovery of its reaction mechanism by Braunstein and Kritzmann in 1937. Their analysis showed that this reversible reaction could be applied to other tissues. This assertion was validated by Rudolf Schoenheimer's work with radioisotopes as tracers in 1937. This in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer.
Another such example of early transferase research and later reclassification involved the discovery of uridyl transferase. In 1953, the enzyme UDP-glucose pyrophosphorylase was shown to be a transferase, when it was found that it could reversibly produce UTP and G1P from UDP-glucose and an organic pyrophosphate.
Another example of historical significance relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This discovery was a large part of the reason for Julius Axelrod's 1970 Nobel Prize in Physiology or Medicine.
Classification of transferases continues to this day, with new ones being discovered frequently. An example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of Drosophila. Initially, the exact mechanism of Pipe was unknown, due to a lack of information on its substrate. Research into Pipe's catalytic activity eliminated the likelihood of it being a heparan sulfate glycosaminoglycan. Further research has shown that Pipe targets the ovarian structures for sulfation. Pipe is currently classified as a Drosophila heparan sulfate 2-O-sulfotransferase.
Nomenclature
s of transferases are constructed in the form of "donor:acceptor grouptransferase." For example, methylamine:L-glutamate N-methyltransferase would be the standard naming convention for the transferase methylamine-glutamate N-methyltransferase, where methylamine is the donor, L-glutamate is the acceptor, and methyltransferase is the EC category grouping. This same action by the transferase can be illustrated as follows:However, other accepted names are more frequently used for transferases, and are often formed as "acceptor grouptransferase" or "donor grouptransferase." For example, a DNA methyltransferase is a transferase that catalyzes the transfer of a methyl group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names. For example, RNA polymerase is the modern common name for what was formerly known as RNA nucleotidyltransferase, a kind of nucleotidyl transferase that transfers nucleotides to the 3' end of a growing RNA strand. In the EC system of classification, the accepted name for RNA polymerase is DNA-directed RNA polymerase.
Classification
Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories. These categories comprise over 450 different unique enzymes. In the EC numbering system, transferases have been given a classification of EC2. Hydrogen is not considered a functional group when it comes to transferase targets; instead, hydrogen transfer is included under oxidoreductases, due to electron transfer considerations.| EC number | Examples | Group transferred |
| EC 2.1 | methyltransferase and formyltransferase | single-carbon groups |
| EC 2.2 | transketolase and transaldolase | aldehyde or ketone groups |
| EC 2.3 | acyltransferase | acyl groups or groups that become alkyl groups during transfer |
| EC 2.4 | glycosyltransferase, hexosyltransferase, and pentosyltransferase | glycosyl groups, as well as hexoses and pentoses |
| EC 2.5 | riboflavin synthase and chlorophyll synthase | alkyl or aryl groups, other than methyl groups |
| EC 2.6 | transaminase, and oximinotransferase | nitrogenous groups |
| EC 2.7 | phosphotransferase, polymerase, and kinase | phosphorus-containing groups; subclasses are based on the acceptor |
| EC 2.8 | sulfurtransferase and sulfotransferase | sulfur-containing groups |
| EC 2.9 | selenotransferase | selenium-containing groups |
| EC 2.10 | molybdenumtransferase and tungstentransferase | molybdenum or tungsten |
Role
EC 2.1: single carbon transferases
EC 2.1 includes enzymes that transfer single-carbon groups. This category consists of transfers of methyl, hydroxymethyl, formyl, carboxy, carbamoyl, and amido groups. Carbamoyltransferases, as an example, transfer a carbamoyl group from one molecule to another. Carbamoyl groups follow the formula NH2CO. In ATCase such a transfer is written as carbamoyl phosphate + L-aspartate L-carbamoyl aspartate + phosphate.EC 2.2: aldehyde and ketone transferases
Enzymes that transfer aldehyde or ketone groups and included in EC 2.2. This category consists of various transketolases and transaldolases. Transaldolase, the namesake of aldehyde transferases, is an important part of the pentose phosphate pathway. The reaction it catalyzes consists of a transfer of a dihydroxyacetone functional group to glyceraldehyde 3-phosphate. The reaction is as follows: sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate erythrose 4-phosphate + fructose 6-phosphate.EC 2.3: acyl transferases
Transfer of acyl groups or acyl groups that become alkyl groups during the process of being transferred are key aspects of EC 2.3. Further, this category also differentiates between amino-acyl and non-amino-acyl groups. Peptidyl transferase is a ribozyme that facilitates formation of peptide bonds during translation. As an aminoacyltransferase, it catalyzes the transfer of a peptide to an aminoacyl-tRNA, following this reaction: peptidyl-tRNAA + aminoacyl-tRNAB tRNAA + peptidyl aminoacyl-tRNAB.EC 2.4: glycosyl, hexosyl, and pentosyl transferases
EC 2.4 includes enzymes that transfer glycosyl groups, as well as those that transfer hexose and pentose. Glycosyltransferase is a subcategory of EC 2.4 transferases that is involved in biosynthesis of disaccharides and polysaccharides through transfer of monosaccharides to other molecules. An example of a prominent glycosyltransferase is lactose synthase which is a dimer possessing two protein subunits. Its primary action is to produce lactose from glucose and UDP-galactose. This occurs via the following pathway: UDP-β-D-galactose + D-glucose UDP + lactose.EC 2.5: alkyl and aryl transferases
EC 2.5 relates to enzymes that transfer alkyl or aryl groups, but does not include methyl groups. This is in contrast to functional groups that become alkyl groups when transferred, as those are included in EC 2.3. EC 2.5 currently only possesses one sub-class: Alkyl and aryl transferases. Cysteine synthase, for example, catalyzes the formation of acetic acids and cysteine from O3-acetyl-L-serine and hydrogen sulfide: O3-acetyl-L-serine + H2S L-cysteine + acetate.EC 2.6: nitrogenous transferases
The grouping consistent with transfer of nitrogenous groups is EC 2.6. This includes enzymes like transaminase, and a very small number of oximinotransferases and other nitrogen group transferring enzymes. EC 2.6 previously included amidinotransferase but it has since been reclassified as a subcategory of EC 2.1. In the case of aspartate transaminase, which can act on tyrosine, phenylalanine, and tryptophan, it reversibly transfers an amino group from one molecule to the other.The reaction, for example, follows the following order: L-aspartate +2-oxoglutarate oxaloacetate + L-glutamate.