Transferase

RNA Polymerase II from S. cerevisiae. Despite the use of the term "polymerase," RNA Polymerases are classified as a form of nucleotidyl transferase.

In biochemistry, transferase is the general name for the class of enzymes that enact the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of different biochemical pathways throughout biology, and are integral to some of life’s most important processes.

Transferase reactions

For example, an enzyme that catalyzed the following reaction would be a transferase: X–Group + Y → X + Y–Group or,

$DonorX+AcceptorY{\xrightarrow[{transferase}]{}}AcceptorX+DonorY$

In the above reaction, X would be the donor, and Y would be the acceptor. "Group" would be the functional group transferred as a result of transferase activity. The donor is often a coenzyme.

Transferases are involved in a myriad of reactions in the cell. Some examples of these reactions include the activity of CoA transferase, which transfers thiol esters, the action of N-acetyltransferase, which is part of the pathway that metabolizes tryptophan, and the regulation of PDH. The regulation of PDH involves both phosphatase, which removes phosphates, and kinase, which adds phosphates. 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.

History and Early Discoveries

Some of the most important discoveries relating to transferases occurred in the early 1950s. 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.

Biodegradation of dopamine via catechol-O-methyltransferase (along with other enzymes). The mechanism for dopamine degradation led to the Nobel Prize in Physiology or Medicine in 1970.

The 1950s

One such example of early transferase reclassification is the discovery and subsequent naming 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.

The 1960s

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 (shared with Sir Bernard Katz and Ulf von Euler).

Nomenclature

Systematic names 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:

methylamine + L-glutamate $\rightleftharpoons$ NH₃ + N-methyl-L-glutamate

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 (based on the EC Number classification). These categories comprise over 450 different unique enzymes. In the EC numbering system, transferases have been given a classification of EC2. It is important to note, that 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.

Classification of transferases into subclasses:

EC number	Examples	Group(s) transfered
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 (e.g. alcohol, carboxyl, etc.)
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

Uses in biotechnology

Transferases are important enzymes used in attaining the goals of Biotechnology. Terminal transferases, for example, are transferases that can be used to label DNA or to produce plasmid vectors. It accomplishes both of these tasks by adding deoxynucleotides in the form of a template to the downstream end or 3' end of an existing DNA molecule.

Glutathione transferases

Glutathione transferases are currently being explored as targets for anti-cancer medications due to their role in drug resistance. Further, glutathione transferase genes have been investigated due to their ability to prevent oxidative damage and have shown improved resistance in transgenic cultigens.

Transferase deficiencies

A deficiency of this transferase, E. coli galactose-1-phosphate uridyltransferase is a known cause of galactosemia

Transferase deficiencies are at the root of many common illnesses. The most common result of a transferase deficiency is a buildup of a cellular product.

SCOT deficiency

Succinyl-CoA:3-ketoacid CoA transferase deficiency (or SCOT deficiency), for example leads to a buildup of ketones. Ketones are created upon the breakdown of fats in the body and are an important energy source. Inability to utilize ketones leads to intermittent ketoacidosis, which usually first manifests during infancy. Disease sufferers experience nausea, vomiting, inability to feed, and breathing difficulties. In extreme cases, ketoacidosis can lead to coma and death. The deficiency is caused by mutation in the gene OXTC1. Treatments mostly rely on controlling the diet of the patient.

CPT-II deficiency

Carnitine palmitoyltransferase II deficiency (also known as CPT-II deficiency) leads to an excess long chain fatty acids, as the body lacks the ability to transport fatty acids into the mitochondria to be processed as a fuel source. The disease is caused by a defect in the gene CPT2. This deficiency will present in patients in one of three ways: lethal neonatal, severe infantile hepatocardiomuscular, and myopathic form. The myopathic is the least severe form of the deficiency and can manifest at any point in the lifespan of the patient. The other two forms appear in infancy. Common symptoms of the lethal neonatal form and the severe infantile forms are liver failure, heart problems, seizures and death. The myopathic form is characterized by muscle pain and weakness following vigorous exercise. Treatment generally includes dietary modifications and carnitine supplements.

Galactosemia

Galactosemia results from an inability to process galactose, a simple sugar. This deficiency occurs when the gene for galactose-1-phosphate uridylyltransferase (GALT) has any number of mutations, leading to a deficiency in the amount of GALT produced.

See also

• EC 2 Introduction from the Department of Chemistry at Queen Mary, University of London