pyridoxine (b6)

Pyridoxine (B6]

Gandham. Rajeev

Department of Biochemistry,Akash Institute of Medical Sciences & Research Centre,Devanahalli, Bangalore, Karnataka, India.

E-Mail: gandhamrajeev33@gmail.com

PYRIDOXINE (B6)

Pyridoxine is a water soluble vitamin

It is a pyridoxine derivative

It consists of 3 closely related compounds

Pyridoxine (alcohol)

Pyridoxal (aldehyde)

Pyridoxamine (amine)

All the components are equally effective as

precursors of coenzyme PLP

PLP is the coenzyme form of pyridoxine

CHEMISTRY

Pyridoxamine is mostly present in plants

Pyridoxal & pyridoxine is present in animal

foods

Pyridoxine can be converted pyridoxal &

pyridoxamine

Pyridoxal phosphate (PLP) is the active form

of Pyridoxine

PLP is synthesized by pyridoxal kinase,

utilizing ATP

CH2OHI

-CH2OH

NH3C--

OH--

Pyridoxine

CHOI

-CH2OH

NH3C--

OH--

Pyridoxal

CH2NH2

I-CH2OH

NH3C--

OH--

Pyridoxamine

ADP

ATPKinase Kinase

ADP

ATP

CHOI

-CH2O-P

NH3C--

OH--

Pyridoxal Phosphate

CH2NH2

I-CH2O-P

NH3C--

OH--

Pyridoxamine Phosphate

COOHI

-CH2OH

NH3C--

OH--

4-Pyridoxic acid

Absorption: It occurs in proximal jejunum by

passive diffusion

In the mucosal cells, all forms of pyridoxine are

converted pyridoxal

Transport: It transported in the circulation

bound to albumin

Storage: It is stored in the tissues as its

coenzyme form, PLP

Mainly stored in liver, brain, kidney & muscle

Excretion: 4 – pyridoxic acid excreted in urine

Metabolism

PLP is the coenzyme of B6 is found attached to ε

–amino group of lysine in the enzyme

PLP is associated with Amino acid metabolism

PLP is involved in

Transamination

Decarboxylation

Deamination

Transsulfuration

condensation

BIOCHEMICAL FUNCTIONS

PLP is involved in transamination reaction

converting amino acids to keto acids

Keto acids enter the TCA cycle & get

oxidized to generate energy

During transamination, PLP interacts with

amino acids to form Schiff base

The amino group is handed over to PLP to

form Pyridoxamine phosphate & ketoacid is

liberated

Transamination

α - Amino acids undergo decarboxylation to

form respective amines

The reaction is carried out by

decarboxylases which require PLP

Serotonin produced from tryptophan is

important in nerve impulse transmission

It regulates sleep, behaviour, blood pressure

Decarboxylation

Tryptophan 5-HydroxyTryptophan

PLP 5-Hydroxytryptamin

eCO2

Histamine is vasodilator & lowers blood

pressure

It stimulates gastric HCL secretion & is

involved in inflammation & allergic reactions

Glutamate on decarboxylation gives GABA

GABA inhibits transmission of nerve

impulses

HistidineDecarboxylase,

PLPHistamine

CO2

Glutamate

PLP GABACO2

The synthesis of catecholamines (dopamine,

nor epinephrine & epinephrine ) from

tyrosine require PLP

PLP is required for synthesis of δ - amino

levulinic acid, the precursor for heme

synthesis

Tryptophan DOPAPLP

Dopamine

CO2

Epinephrine

Nor epinephrine

Glycineδ - Amino levulinic

acidPLP

HemeSuccinyl CoA

ALA synthase

The synthesis of niacin coenzymes (NAD+ &

NADP+ ) from tryptophan require PLP

Kynureninase require PLP

NAD+NADP+

Xanthurenic acidIncreased in B6

deficiency

PLP

3-Hydroxy anthranilic acid

3-Hydroxykynurenine

Tryptophan

Kynureninase

PLP Plays an important role in metabolism of

sulfur containing amino acids

Transsulfuration from homocysteine to serine

occurs in the synthesis of cysteine

PLP dependent enzyme cystathionine

synthase

Taurine, a decarboxylated product of cysteine

is formed

Deamination of hydroxyl group containing

amino acids require PLPSerine

Pyruvate + NH3PLP

Dehydratase

Synthesis of serine from glycine require PLP by

an enzyme hydroxymethyl transferase

The enzyme glycogen phosphorylase

containes PLP

It converts glycogen to glucose 1-phosphate

PLP is needed for the absorption of amino acids

from intestine

B6 is useful to prevent urinary stone

formation

Threonineα - Ketobutyrate +

NH3PLP

Dehydratase

Adult men – 2 - 2.2

mg/day

Adult women - 2.0 mg/day

Pregnancy & lactation - 2.5 mg/day

Dietary sources:

Animal sources

Egg yolk, fish, milk, meat

Vegetable sources

Wheat, corn, cabbage, roots & tubers

RDA

Decreased dietary intake

Alcoholism

Impaired absorption

Antivitamins: chronic administration of drugs

such as isoniazid & penicillamine

Clinical features:

Neurological manifestations:

Due to B6 deficiency, serotonin, epinephrine,

noradrenaline & GABA are not produced

properly

Deficiency

In children B6 deficiency leads to convulsions

due to decreased formation of GABA

PLP is required for synthesis of sphingolipids

Its deficiency leads to demyelination of

nerves & peripheral neuritis

This is reversible with high doses of B6

Dermatological manifestations

B6 deficiency is associated with tryptophan

metabolism

B6 deficiency leads to pallagra

The synthesis of niacin from tryptophan is

impaired

Xanthurenic acid, produced in high

quantities is excreted in urine

It serves as a reliable index of B6 deficiency

Decreased Hb levels, associated with

hypochromic micytic anemia seen in B6

deficiency

Isonicotinic acid hydrazide is antituberculosis

drug

It inhibits pyridoxal kinase, reduces the

formation of PLP

Cycloserine: It act as B6 antagonist

Oral contrceptives:

Seen in women taking oral contraceptive pills

Ethanol, it is converted to acetaldehyde,

which inactivates PLP

B6 deficiency neuritis common in alcoholics

Effect of drugs on vitamin B6:

Toxicity of B6:Excess use of B6 (2.5 g/day) may lead to

sensory neuropathy

It is manifested by imbalance, numbness,

muscle weakness and nerve damage

References

Harper’s Biochemistry 25th Edition.

Fundamentals of Clinical Chemistry by Tietz.

Text Book of Medical Biochemistry-A R Aroor.

Text Book of Biochemistry-DM Vasudevan

Text Book of Biochemistry-MN Chatterjea

Text Book of Biochemistry-Dr.U.Satyanarana