Pyridoxal-phosphate is a prosthetic group of some enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s. It is the active form of vitamin B₆

Vitamin B6

Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

, which comprises three natural organic compounds, pyridoxal

Pyridoxal

Pyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...

, pyridoxamine

Pyridoxamine

Pyridoxamine is a vitamer in the vitamin B6 family, which includes pyridoxal and pyridoxine. Pyridoxamine is converted to the biologically active form of vitamin B6, pyridoxal 5-phosphate, via the vitamin B6 salvage pathway. Vitamin B6 acts as an enzyme cofactor in a variety of metabolic processes...

 and pyridoxine

Pyridoxine

Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...

.

Role as a coenzyme

PLP acts as a coenzyme in all transamination

Transamination

There are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...

 reactions, and in some decarboxylation

Decarboxylation

Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

 and deamination

Deamination

Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...

 reactions of amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s. The aldehyde group of PLP forms a Schiff-base

Schiff base

A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....

 linkage (internal aldimine) with the ε-amino group of a specific lysine group of the aminotransferase enzyme. The α-amino group of the amino acid substrate displaces the ε-amino group of the active-site lysine residue. The resulting external aldimine becomes deprotonated to become a quinoid intermediate, which in turn accepts a proton at a different position to become a ketimine. The resulting ketimine is hydrolysed so that the amino group remains on the complex.

In addition, PLP is used by aminotransferases (or transaminases) that act upon unusual sugars such as perosamine

Perosamine

Perosamine is a mannose-derived 4-aminodeoxysugar produced by some bacteria.-Biological role:N-acetyl-perosamine is found in the O-antigen of Gram-negative bacteria such as Vibrio cholarae O1, E. coli O157:H7 and Caulobacter crescentus CB15...

 and desosamine

Desosamine

Desosamine is a 3--3,4,6-trideoxyhexose found in certain macrolide antibiotics such as the commonly prescribed erythromycin.-Biosynthesis:Six enzymes are required for its biosynthesis from TDP-glucose in Streptomyces venezuelae....

. In these reactions, the PLP reacts with glutamate, which transfers its alpha-amino group to PLP to make pyridoxamine phosphate (PMP). PMP then transfers its nitrogen to the sugar, making an amino sugar

Amino sugar

In chemistry, an amino sugar contains an amine group in place of a hydroxyl group. Derivatives of amine containing sugars, such as N-acetylglucosamine and sialic acid, while not formally containing an amine, are also considered amino sugars....

.

PLP is also involved in various beta-elimination reactions such as the reactions carried out by serine dehydratase

Serine dehydratase

Serine Dehydratase or L-Serine Ammonia Lyase is in the ß-family of Pyridoxal Phosphate-dependent enzymes. SDH is found widely in nature, but its structural and chemical properties vary greatly among species. SDH is found in yeast, bacteria, and the cytoplasm of mammalian hepatocytes...

 and GDP-4-keto-6-deoxymannose-3-dehydratase (ColD)

Cold

Cold describes the condition of low temperature.Cold may also refer to:*Common cold, a contagious viral infectious disease of the upper respiratory system*Chronic obstructive pulmonary disease...

.

It is also active in the condensation reaction in heme

Heme

A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

 synthesis.

PLP plays a role in the conversion of dopa

Dopa

Dopa or DOPA can refer to:* L-DOPA , used in the treatment of Parkinson's disease* D-DOPA, a chemical compound related to L-DOPA* Dopa, an angel in Enochian* Deleting Online Predators Act of 2006...

 into dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, allows the conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA

Gabâ

Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...

, and allows SAM

S-Adenosyl methionine

S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...

 to be decarboxylated to form propylamine

Propylamine

Propylamine, also known as n-propylamine, is an amine with the chemical formula C3H9N.Propylamine is a weak base with its Kb equaling 4.7 × 10-4.-Preparation:...

, which is a precursor to polyamines.

Non-classical examples of PLP

PLP is also found on glycogen phosphorylase in the liver, where it is used to break down glycogen

Glycogen

Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

 in glycogenolysis

Glycogenolysis

Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...

 when glucagon

Glucagon

Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 or epinephrine

Epinephrine

Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 signals it to do so. However, this enzyme does not exploit the reactive aldehyde group, but instead utilizes the phosphate group on PLP to perform its reaction.

Although the vast majority of PLP-dependent enzymes form an internal aldimine with PLP via an active site lysine residue; some PLP-dependent enzymes do not have this lysine residue, but instead have an active site histidine. In such a case, the histidine cannot form the internal aldimine, and, therefore, the cofactor never becomes covalently tethered to the enzyme. GDP-4-keto-6-deoxymannose-3-dehydratase (ColD)

Cold

Cold describes the condition of low temperature.Cold may also refer to:*Common cold, a contagious viral infectious disease of the upper respiratory system*Chronic obstructive pulmonary disease...

 is an example of such an enzyme.

Catalytic Mechanism

The pyridoxal-5′-phosphate-dependent enzymes (PLP enzymes) catalyze myriad biochemical reactions. Although the scope of PLP-catalyzed reactions initially appears to be immensely diverse, there is a simple unifying principle: In the resting state, the cofactor (PLP) is covalently bonded to the amino group of an active site lysine, forming an internal aldimine. Once the amino substrate interacts with the active site, a new Schiff base is generated, commonly referred to as the external aldimine. Only after this step, the mechanistic pathway for each PLP-catalyzed reaction diverges. Density functional methods have been applied to investigate the transimination reaction, and the results have shown that the reaction involves three sequential steps: (i) formation of a tetrahedral intermediate with the active site lysine and the amino substrate bonded to the PLP cofactor; (ii) nondirect proton transfer between the amino substrate and the lysine residue; and (iii) formation of the external aldimine after the dissociation of the lysine residue. The overall reaction is exothermic (−12.0 kcal/mol), and the rate-limiting step is the second one with 12.6 kcal/mol for the activation energy

Biological Synthesis

It is synthesized from pyridoxal by the enzyme pyridoxal kinase

Pyridoxal kinase

In enzymology, a pyridoxal kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and pyridoxal, whereas its two products are ADP and pyridoxal 5'-phosphate....

, requiring one ATP. It is metabolized in the liver.