Role of Vitamin B6 in Protein Metabolism

Vitamin B complex consist of  water soluble Vitamins which were earlier thought of as being a single Vitamin but later found to be composed of  EIGHT chemically distinct Vitamins. One of these eight vitamins is vitamin B6 or Pyridoxal.

Sources of vitamin B6 in food include

·         Royal Jelly of Bees

·         Yeast

·         Rice Polishing

·         Cereal Grains

·         Egg Yolk

·         Germinal portion of various Seeds

Structure of vitamin B6

Vitamin B6 consists of derivatives of  Purine Ring. This vitamin is Biochemically active only when in Phosphorylated form. This Phosphorylation is brought about by Kinase enzyme that bring about this Phophorylation  at 5^th Position.

Isoforms

Vitamin B6 exists as six isoforms. Which include:

·         Pyridoxine

·         Pyridoxine-P

·         Pyridoxal

·         Pyridoxal-P

·         Pyridoxamine

·         Pyridoxamine-P

·          

The Biologically active forms of vitamin B6 are

a)      Pyridoxal-PO₄

b)      Pyridoxamine-PO₄

Role in amino acid metabolism

Vitamin B₆ is actually the generic name for the precursors of the coenzyme pyridoxal phosphate (PLP). When dietary form of vitamin B6 is taken the phosphate of this coenzyme is removed by intestinal alkaline phosphates, and only the dephosphorylated forms are absorbed. The total body content of PLP is only 25 mg in adults, the circulating form of this vitamin are Pyridoxal and PLP. Several enzymes Involved in amino acid metabolism have PLP as a tightly bound prosthetic group. In these reactions, the aldehyde group of PLP forms an aldimine derivative with the amino group of the amino acid. The aldimine is stabilized by a hydrogen bond with the phenolic hydroxyl group

Pyridoxal phosphate is involved in almost all amino acid metabolisms, from synthesis to breakdown.

Transamination

The Transaminases are the enzymes that break down amino acids. They are dependent on the presence of Pyridoxal phosphate. These enzymes are needed for the process of moving amine groups from one amino acid to another. These Transaminases catalyze the transfer of  NH2 groups from the amino acids, onto alpha-ketoglutarate.  Naturally Many different transaminases are known, and all require the same co-factor  Pyridoxal phosphate (vitamin B6).

Mechanism of Transamination

PLP plays a central role here in the inter conversion of an amino acid and an alpha-keto acid.
(1) Transaminase first bind to pyridoxal phosphate in a Schiff-base link to a Lysine residue of enzyme. This leads to the formation of an "aldimine".
(2) As a new substrate enters the active site, its amino group displaces the -NH₂ of active site Lysine. Then a new Schiff-base link is formed to the alpha-amino group of the substrate, as the active site Lysine moves aside.
(3) There is an electronic rearrangement resulting in shifting the double bond to form a "ketimine".
(4) This formation of ketimine is followed by hydrolysis to release PMP and an alpha-keto acid.
(5) PMP combines with alpha-ketoglutarate in a reversal of steps 1-4. The net result is transfer of an amino group to alpha-ketoglutarate, and release of glutamate, while regenerating the PLP-enzyme complex.

Trans-sulfuration

 Cystathionine synthase and cystathionase need pyridoxal phosphate for proper functioning. These enzymes transform methionine into cysteine. Cystathionine-β-synthase, which is also known as CBS, is an enzyme that is encoded by the CBS gene. It catalyzes the first step of the transsulfuration pathway. CBS also uses the cofactor pyridoxal-phosphate (PLP) 

Selenoamino acid metabolism

 The primary dietary form of selenium is Selenomethionine. For the use of selenium as a nutrient Pyrodixal phosphate act as a co-factor. Pyridoxal phosphate also act as a co-factor in breaking of selenohomocystein to release selenium to produce hydrogen selenide, which can then be used to incorporate selenium into selenoproteins to be used for various cellular functions.

Conversion of tryptophan to niacin vitamin B6

The liver synthesize niacin from tryptophan, liver requires 60 mg of tryptophan to make one mg of niacin. The 5 membered aromaticheterocycle of tryptophan is cleaved and then it is rearranged with the alpha amino group of tryptophan into the 6-membered aromatic heterocycle of niacin. 

Decarboxylation Reactions

Decarboxylation reactions require vitamin b6 as coenzyme for enzymes decarboxylase that is involved in removal of CO₂ to produce AMINES. For example during the conversion of histidine to histamine decarboxylation occurs as removal of CO2 happens and use vitamin b6 as co-enzyme. Other decarboxylation reactions that use vitamin B6 as coenzyme include the conversion of glutamine acid to Gama amino butaric acid (GABA) and conversion of 5-OH Tryptophan to 5-OH Tryptamine (Serotonin) .

Other uses of vitamin B6

1.      Synthesis of sphingosine

2.      Intramitochondrail fatty acid synthesis

3.      Transport of K.

Vitamin B6 deficiency

The deficiency of vitamin B6 occurs rarely and is often associated with malabsorption syndromes and alcoholism. Certain drugs are also thought to cause its deficiency by rendering the vitamin inactive these drugs include isoniazid hydrolazine and penicillamine.

The symptoms of Vitamin B6 deficiency in adults include.

·         Nervousness

·         Irritability

·         Insomnia

·         Muscle weakness

·         Difficulty in walking

·         Glossitis

·         Cheliosis

·         Seizures

Vitamin B₆ deficiency can be prevented or treated with consumption of the recommended dietary allowance, as supplied by food or by vitamin supplements.