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Vitamin B2

VitB2

Riboflavin - Flavin adenine dinucleotide (FAD); flavin mononucleotide (FMN)

VitB2

Daily Requirement:

Modified DV:

RDA ?:

Adequate Intake ?:

1.3

true

mg/day

mg/day

Min Deficiency:

Max Toxicity:

Tolerable UL

Animal:Plant Conv:

0

mg/day

mg/day

mg/day

Date Discovered:

1933

Short Description:

Electron (hydrogen) transfer reactions for nutrient metabolism and energy production. Ariboflavinosis -- Cheilosis, glossitis, angular stomatitis, edema oral cavity, dermatitis. Major Food Sources: Meats, eggs, yougurt, cheese, milk. RDA: 1.3 mg

Interpretation:

Typically highest in animal sourced foods including liver, meat, eggs, dairy.


Other good sources include nuts, pulses, dark green leafy vegetables.


Milling of white rice and cereals results in 2/3rd loss of riboflavin.


Two main active forms in animals and plants

  • Riboflavin-mononucleotide (FMN)

  • Riboflavin-adenine dinucleotide (FAD)

Impaired mitochondrial metabolism suspected in patients with migraines: Riboflavin catalyzes the activity of flavoenzymes in
the mitochondrial respiratory chain.


  • Ariboflavinosis: main deficiency

  • The signs and symptoms include skin disorders, hyperemia (excess blood) and edema of the mouth and throat, angular stomatitis (lesions at the corners of the mouth), cheilosis (swollen, cracked lips), hair loss, and reproductive problems.

  • Rarely occurs in isolation as b-vitamins are usually available in
    similar foods. 

  • Many foods rich in thiamin are also rich in riboflavin.

History & Discovery:

In 1879, Alexander Wynter Blyth, a English chemist, described water-soluble material from milk that glowed with a yellow-green fluorescence when exposed to light. He called lactochrome, ‘lacto’ (milk) and ‘chrome’ meaning color because of the yellow pigment.


In 1933-1935, Kuhn and Karrer, two Austrian scientists and Nobel Prize winners, isolated lactoflavin from milk and found the same chacteristics described by Blyth. They described the structure of riboflavin.

Digestion:

Riboflavin occurs in most foods as protein complexes of the co-enzyme forms FMN and FAD, uptake depends on hydrolytic conversion to free riboflavin.


FAD -> FAD pyrophosphatase -> FMN -> FMN phosphatase -> Riboflavin


This occurs through protelytic activity in the lumen by intestinal brush border phophatases, which liberate riboflavin to its free form where it can be transported across the intestinal brush borders (intestinal villi) using riboflavin vitamin transporters (RFVTs).


Jejunum is primary site of absorption.


  • RVFT3 carries riboflavin across the brush border membrane.

  • RFVT1 and RFVT2 carries riboflavin across the basolateral membrane of the intestinal cell. 

  • RFVT2 is present in high amounts in tissues and transports riboflavin into tissues.



Absorption and Storage:

Blood:

  • Riboflavin

  • FAD

  • FMN (40%)

Uptake:

  • Usually bound to proteins such as albumin

  • Primary uptake into tissue is through RFVT2 as free riboflavin.

  • Following uptake riboflavin is converted to FMN through riboflavin kinase in an ATP dependent process.

  • Kinases catalyze the transfer of a phosphate from ATP to a specified molecule.

  • Then FMN is converted to FAD by FAD synthase.

  • Kinases catalyze the linking together of two molecules, without ATP.


Important Pathways:

Oxidative decarboxylation of pyruvate and α-ketoglutarate:

FAD serves as an electron carrier (high redox potential) meaning it takes the electrons from pyruvate and α-ketoglutarate and is transformed into FADH2.


Succinate dehydrogenase: removes electrons from succinic acid to form fumarate, and forms FADH2. The electrons are then passed into the electron transport chain by coenzyme Q10 (CoQ10).

Glutathione reductase is "recharged" by FAD


Riboflavin: anti-oxidant roles


Thioredoxins are ubiquitous antioxidant enzymes that play important roles in many health-related cellular processes including protection from cancer and viral diseases.


FAD transfers reducing equivalents from NADPH through its bound FAD to reduce disulfide bonds within the oxidized form of thioredoxin to bring it back to a reduced state. Reduced thioredoxin has a radical-scavening activity. 


  • Reduction of ribonucleotides to deoxyribonucleotides by ribonucleotide reductase

  • Riboflavin: Co-factor for other vitamins

  • Pyridoxine (PN) -> phosphatase -> Pyridoxine-PO4 (PNP) -> oxidase (FMN) -> Pyridoxal-PO4 (PLP) = primary form of Vit B6

  • Pyridoxal (PL) -> phosphatase -> Pyridoxal-PO4 (PLP) = primary form of Vit B6

  • Pyridoxamine (PM) -> phosphatase -> Pyridoxamine-PO4 (PMP) -> oxidase (FMN) -> Pyridoxal-PO4 (PLP) = primary form of Vit B6

  • FAD-dependent -> Retinal aldehyde

  • Tryptophan can be converted to niacin using FAD and B6

  • Riboflavin involved in the breakdown of neurotransmitters like dopamine


Deficiency Diseases, Detection, Cures:

Symptoms:

  • Cheilosis and/or glossitis

  • Nausea and vomiting and/or diarrhea

  • Pigmentation changes, erythema

  • Dermatitis

  • Neuropathy

  • Nervous system - general effects

  • Photophobia

Genetic Diseases:

References:

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