RIBOFLAVIN (B2]

Gandham. Rajeev

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

E-Mail: gandhamrajeev33@gmail.com

Riboflavin

STRUCTURE

• Riboflavin is a yellow pigment

• Riboflavin contains 6,7 – dimethyl

isoalloxazine ring attached to D-ribitol by

a nitrogen atom

• Ribitol is an open chain form of sugar

ribose with aldehyde group is reduced to

alcohol

• It emits yellow fluorescence

• It is stable to heat but sensitive to light

• When exposed to UV rays of sun light, it is

converted to lumiflavin which exhibits

yellow fluorescence

• Lactoflavin from milk

• Hepatoflavin from liver

• Ovoflavin from eggs are structurally

identical to riboflavin

Structure of Riboflavin

N

NH

O

O

N

N

H3C

H3C

I H - C - OH

IH3C

I H - C - OH

I H - C - OH

ICH2OH

RIBITOL

Riboflavin

ATP

ADP

Flavokinase

Isoalloxine ring

N

NH

O

O

N

N

H3C

H3C

I H - C - OH

IH3C

I H - C - OH

I H - C – OH

ICH2 O - P – O-

FMNATP

PPiFAD synthase

O

O

N

NH

O

O

N

N

H3C

H3C

I H - C - OH

IH3C

I H - C - OH

I H - C – OH

ICH2 O - P – O

FAD

O

O

- P – O

O

O

-CH2

H

N

N

NH2

IN

N

H

• Absorption:

• Riboflavin is present in the food as FAD, FMN

and free riboflavin

• FMN & FAD are hydrolysed to free form in

upper small intestine

• Free form is absorbed by intestinal mucosal

cells by sodium dependent transport system

• Transport:

• In the intestinal mucosal cells riboflavin is

converted into FMN by the action of

flavokinase in the presence of ATP

• FMN enters the portal circulation

• In the plasma it is transported as Albumin-

FMN complex

• FMN complex enters the tissues including liver

• In the tissues it is converted into FAD

• Storage:

• Riboflavin is mainly stored in liver

• It is stored as FMN & FAD

• Excretion:

• Mainly excreted in urine

• Coenzymes of Riboflavin:

• FMN & FAD

• The Ribitol is linked to phosphate in FMN

• FAD is formed from FMN by transfer of an

AMP from ATP

• Biochemical functions:

• FAD & FMN participate in many redox

reactions responsible for energy production

• The functional unit is isoalloxazine ring,

serves as an acceptor of two hydrogen atoms

• FMN or FAD undergo identical reversible

reactions accepting 2H atoms forming

FMNH2 or FADH2

• Flavoproteins:

• The enzymes that use flavin coenzymes are

called as flavoproteins

• Metalloflavoproteins:

• Many flavoproteins contain metal atoms

(iron,molybdenum etc) which are known as

metalloflavoproteins

Reactions requiring FMN

• FMN is the prosthetic group of L – amino acid

oxidase & NADH dehydrogenase

(1) NADH dehydrogenase catalyzes the

transfer electrons from NADH coenzyme

• In this, FMN is involved in transfer of

electrons from NADH to iron sulfur proteins

• Electrons are then transferred to Coenzyme

Q

(2) L – Amino acid oxidase:• It catalyzes the conversion of L-amino acid to

the α-ketoacid • Ammonia is released & FMN is reduced to

FMNH2

NADH + H+ + FMN

NAD + FMNH2

NADH Dehydrogenase

L-Amino acid + FMN

α- Keto acid + NH3 + FMNH2

L – amino acid oxidase

Reactions requiring FAD

• Enzymes containing FAD

• Carbohydrate metabolism:

• PDH Complex:

• PDH complex catalyzes the oxidative

decarboxylation of pyruvate to acetyl CoA

• NAD is reduced to NADH + H+

• FAD is present in Dihydrolipoyl

dehydrogenase of PDHPyruvate

Acetyl CoA

PDH ComplexFAD

NAD

NADH + H+

• α- Ketoglutarate dehydrogenase complex:

• It catalyzes the oxidative decarboxylation of

α- Ketoglutarate to succinyl CoA

• FAD is present in dihydrolipoyl

dehydrogenase of α- Ketoglutarate

dehydrogenase complex

α- Ketoglutarate

Succinyl CoA

α- KetoglutarateComplexFAD

NAD

NADH + H+

CoA SH

CO2

• Succinate dehydrogenase:

• It catalyzes the oxidation of succinate to

fumarate

• FAD is reduced to FADH2

Succinate

FAD

Fumarate

Succinate Dehydrogenase

FADH2

LIPID METABOLISM

• Acyl CoA Dehydrogenase:

• It catalyses the Oxidation of fatty acyl CoA

to 2, 3 unsaturated acyl CoA

Fatty acyl CoA

2, 3 unsaturated acyl CoA

Acyl CoA dehydrogenaseFAD

FADH2

Mitochondrial Glycerol 3-P dehydrogenase

• It catalyzes the conversion of glycerol 3P to

DHAP in mitochondria

• It essential for carrying reducing equivalents

from cytosol to mitochondria

Glycerol 3-phosphate

DHAP

Mitochondrial glycerol 3-P dehydrogenase

FAD

FADH2

Protein metabolism

• Glycine cleavage system:

• It catalyzes the conversion of glycine to CO2

and ammonia

• FH4 is converted into N 5,10 methylene FH4

Glycine + FH4

N 5,10 methylene FH4 + CO2 + NH3

Glycine cleavage system

D – Amino acid Oxidase

• It catalyzes the conversion of D – amino

acids or glycine to corresponding ketoacids

• Ammonia is reduced

• FAD is reduced to FADH2

D – Amino acid + FAD

α - Keto acid + NH3 + FADH2

D – Amino acid Oxidase

Purine metabolism

• Xanthine Oxidase:

• It catalyzes the oxidation of hypoxanthine

to xanthine and xanthine to uric acid

• Xanthine oxidase contains FAD,

molybdenum and ironHypoxanthine

Xanthine

Xanthine oxidaseFAD

FADH2

Uric acid

Xanthine oxidase

Dietary sources

• Rich sources are milk, milk products,

meat,eggs, liver and kidney

• Moderate sources are cereals, fruits,

vegetables and fish

• RDA:

• Men - 1.5 mg/day

• Women - 1.2 mg/day

• Pregnancy & lactation - 1.5 mg/day

+ Deficiency

• Causes:

• Inadequate intake

• Impaired absorption due to intestinal diseases

• Chronic alcoholics are susceptible to B2

deficiency

• Clinical features:

• Cheilosis (fissures at the corners of mouth)

• Glossitis (tongue smooth and purplish)

• Dermatitis

• Corneal vasculalarization: includes dryness,

burning & itching and lacrimination

• Measurement of glutathione reductase in

erythrocytes is a reliable diagnostic test to

assess riboflavin deficiency

• Reference interval

• Serum or plasma level is 4 to 24 µg/ dl

Dermatitis, Riboflavin deficiency

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