Vitamin B2 (Riboflavin)

Chemistry
Metabolism
Metabolic role of riboflavin
Excretion of riboflavin
Sources of riboflavin
Requirements
Deficiency symptoms
Toxicity

I.  Chemistry

  1. Riboflavin contains D ribose. The name comes from Ribo (ribose) and flavin (flavus-Latin for yellow)
  2. Structure (see figure 9.15 from Groff, J.L., S.S. Gropper, and S.M. Hunt 1995. Advanced Nutrition and Human Metabolism. West Publ. Co., St. Paul, MN)
  3. Physical properties
    1. Yellow to orange yellow crystalline powder
    2. Slightly soluble in water, dilute acids, and alcohol. Soluble in alkaline solutions but subject to destruction
    3. Stable in dry form
    4. Unstable in light, forms lumiflavin or lumichrome

II.  Metabolism

  1. Absorption and transport
    1. Riboflavin in foods attached to protein or as FAD, FMN, and riboflavin phosphate must be freed prior to absorption
      1. HCL or intestinal enzymatic hydrolysis of protein
      2. FAD  FAD pyrophosphatase® FMN FMN phosphatase® riboflavin in intestines
    2. Free riboflavin is absorbed via a saturable, Na-dependent carrier mechanism primarily in proximal small intestine
      1. Absorption requires ATP
      2. Absorption rate is proportional to dose up to approximately 25 mg/day
    3. On absorption into mucosal cells, riboflavin is phosphorylated into FMN
      1. Catalyzed by flavokinase
      2. Requires ATP
    4. At serosal surface, FMN is dephosphorylated to riboflavin which enters the portal system
    5. Riboflavin is carried to the liver where it is converted to its coenzyme derivatives (see figure 9.15 from Groff et al. 1995)
    6. Riboflavin, FMN, and FAD are transported in the plasma by a variety of proteins
      1. Albumin (primary transport protein)
      2. Fibrinogen
      3. Globulins (principally immunoglobulins)
      4. Most of flavins in plasma are found as riboflavin rather than its coenzyme forms
    7. Free riboflavin crosses cell membranes in tile tissues by a carrier - mediated process
    8. Within the cell, riboflavin is converted to its coenzyme forms by flavokinase and FAD synthetase
    9. A high-affinity transport system for riboflavin coenzymes may exist in the brain
      1. Concentration of FAD in the brain is maintained even in severe riboflavin deficiency
    10. FMN and FAD function as prosthetic groups for enzymes involved in oxidation reductions (flavoproteins)

III.  Metabolic role of riboflavin

  1. FMN and FAD function as cofactors for a wide variety of oxidative enzyme systems
    1. Act as oxidizing agents because of their ability to accept a pair of hydrogen atoms
    2. Isoalloxazine ring is reduced by two successive one-electron transfers
    3. FMNH2 and FADH2 are cofactors for reduced forms of the flavoprotein
  2. Roles of flavoproteins in intermediary metabolism
    1. Oxidative decarboxylation of pyruvate and a-ketoglutarate
    2. Succinic dehydrogenase removes electrons from succinate to form fumarate
    3. The electrons are passed into the electron transport chain via coenzyme Q
    4. Fatty acyl CoA dehydrogenase require FAD in fatty acid oxidation
    5. As a coenzyme for xanthine oxidase, FAD transfers electrons directly to oxygen
      1. The enzyme contains FAD, Fe, and Mo
      2. It converts hypo xanthine to xanthine to uric acid
    6. Aldehyde oxidase uses FAD to oxidize aldehydes
      1. Pyridoxal (vitamin B6) ® pyridoxic acid (excreted)
      2. Retinal (vitamin A) ® retinoic acid
    7. Pyridoxine phosphate oxidase which converts pyridoxamine phosphate and pyridoxine phosphate to pyridoxal phosphate (primary coenzyme form of vitamin B6 is dependent on FMN
    8. Synthesis of an active form of folate, N5 methyl tetrahydrofolate, requires FADH2
    9. Enzymes for choline catabolism require FAD
      1. Choline dehydrogenase
      2. Dimethylglycine dehydrogenase
    10. Metabolism of some amines requires FAD-dependent monoamine oxidase
      1. Dopamine
      2. Tyramine
      3. Histamine
    11. Reduction of GSSG to GSH is dependent on FAD-dependent glutathione reductase

IV.  Excretion of riboflavin

  1. Urine is the primary route and is dependent on circulating levels; bile is a secondary route
  2. Main excretory product is free riboflavin
  3. Orally administered riboflavin appears in urine within hours

V. Sources of riboflavin

  1. Food sources:
    Best Good Fair
    Milk
    Egg white
    Liver
    Heart
    Green vegetables
    Beef
    Veal
    Poultry
    Apricot
    Tomato
    Yeast
    Fish
    Legumes
    Unenriched grains
  2. Feed sources:
    1. Alfalfa
    2. Other green leafy forages
    3. Certain meat byproducts
    4. Oil meals
    5. Whey

VI.  Requirements

  1. Requirement appears to be related to energy intake
  2. Physiologic factors, chronic disorders, and drugs which increase likelihood of deficiency
    1. Congenital heart disease
    2. Some cancers
    3. Thyroid disease
    4. Diabetes mellitus
    5. Trauma
    6. Stress
    7. Oral contraceptives
  3. Mg/kg DM in livestock feed:
    Species Growth Reproduction
    Pig
    Chick
    Turkey
    2.3 - 3
    1.8 - 3.6
    3.6
    3.4 - 4.1
    3.8
    3.8
  4. RDA for human is 1.5 mg/day, increased during pregnancy and lactation

VII.  Deficiency symptoms

  1. Rat – Symmetrical alopecia, dermatitis with serious exudate that can stick eyelids shut, growth failure, cataract formation, corneal opacities, conjunctivitis, vascularization of tile cornea
  2. Dog – Reduced heart rate, cardiac arrythmia, collapse, coma
  3. Pig – Reduced growth, corneal opacities and cataracts, dermatitis, thickened skin, crooked and stiff legs, reproductive failure
  4. Birds – Degeneration of myelin sheath of nerves, "curled-toe paralysis", reduced hatchability
  5. Human – Originally confused with pellagra
    1. Oral and facial lesions.
      1. Outside of the lips and corners of the mouth
      2. Red and swollen tongue
    2. Itching dermatitis, scaly, greasy skin
    3. Conjunctivitis, lacrimation, burning of the eyes, corneal vascularization
    4. Peripheral nerve dysfunction
    5. Severe deficiency
      1. Diminished synthesis of coenzyme form of vitamin B6
      2. Diminished synthesis of niacin (NAD) from tryplophan

VIII.  Toxicity

  1. Toxicity is unlikely
  2. Bright yellow hair and skin have been observed with large dosages




MD's Choice Nutritional Products
For individual consultation or questions about our products, call
1-800-628-0997

Click Here for a Printable Version of This Page