Riboflavin Flashcards
What are the properties of riboflavin?
- From flavus = yellow and ribose=sugar
- Yellow/orange crystal
- Heat stable
- Water soluble (reasonably)
- Unstable in UV light and alkaline solutions
What are the active forms of riboflavin?
- 2 different cofactors:
1. FMN = flavin mononucleotide (riboflavin-5-phosphate) phosphorylated form
2. FAD = flavin adenine dinucleotide (riboflavin-5-adenosyl-diphosphate) - gets an adenine added
Riboflavin phosphorylated to FMN by flavokinase, FMN phosphorylated to FAD by FAD synthetase
What minerals are needed for riboflavin to be activated?
- Zinc and Magnesium
What hormone is important for riboflavin and why?
- Conversion of free form to FMN and FAD regulated by thyroid hormone
- Increases flavokinase activity
- Hypothyroidism thus causes a functional deficiency in riboflavin
What are the structures of riboflavin?
- Riboflavin
- FMN = Riboflavin + phosphate
- FAD = Riboflavin + AMP
- Some proteins use FAD and others receive FMN
What is riboflavins mode of action?
- FMN and FAD cofactor for >100 flavoproteins
- FMN and FAD can accept 2 H-atoms from substrate
→ important in redox reactions, dehydrogenations, hydroxylations, oxidative decarboxylations, dioxygenations
FMN and FAD can carry hydrogens - Double bonds on the nitrogens that can accept hydrogens and or else give them up, goes both ways
→ reduced have gained hydrogens (extra bonds)
What is the metabolic role of riboflavin?
- Energy production - carry reducing equivalents into the mitochondrial respiratory chain
→ TCA cycle
→ ETC
→ B-oxidation of fatty acids (much of the energy production learned about last semester riboflavin has a role in) - Regulation of redox status
- Detoxification (FMOs)
- Conversion of vitamins (B6 and folate) into their coenzyme form
- Synthesis of niacin (B3) from tryptophan
How is riboflavin involved in the CAC cycle?
- involved in the succinate dehydrogenase reaction, PDH reaction
- alpha ketoglutarate use thiamin as well!
How is riboflavin involved in the PDH complex?
- Step 4 of the PDH complex has FAD to FADH2
- Need riboflavin to convert pyruvate to acetyl coA!
Why is riboflavin needed for the succinate dehydrogenase reaction?
- Succinate converted to fumarate by succinate dehydrogenase using FAD cofactor
- Oxidative reaction
How is riboflavin involved in the electron transport chain?
- Complex 1 and 2
- Complex 2 uses FAD and succinate dehydrogenase
- Complex 1 uses FMNand NADH dehydrogenase module
- Transfer of H+ which can be used to generate ATP
What is riboflavin’s role in beta-oxidation of fatty acids?
- Involved in reduction of palmitoyl coA (fatty acid) to trans delta2 enoyl-CoA by acyl dehydrogenase
- NAD and CoASH (Thiamin) used in later steps to convert to Acyl CoA
Riboflavin is also called?
B2
What are the sources of riboflavin?
Gut is exposed to flavins from 2 sources:
1. Diet
2. Flavins synthesized by bacteria in the large intestine
- Unknown whether this is available to host tissues (besides colonic epithelial cells)
- Synthesis increased with vegetarian diet versus meat-based diet
What are the riboflavin requirements?
- depends on energy intake and other nutrients (including protein)
- UL is not set because no reported cases of riboflavin toxicity
→ may be due to low solubility and prompt excretion
What are the populations at risk of riboflavin deficiency?
- Low intake
→ Common in China, India, Africa, and Thailand: deficiency is endemic where diets lack dairy products and meat
→ Elderly - Pregnancy
- Disease states:
→ Thyroid
→ Diabetes
→ Hyperbilirubinemia
What 3 other nutrients is riboflavin deficiency associated with?
- Iron
- Iron absorption and mobilization require reduction of Fe3+ to Fe2+
- Flavins are most efficient reductants - Vitamin B6
- Enzyme that converts B6 to active form requires FMN
- May also affect other kinases and phosphatases involved with B6 metabolism - Folate
- Final step in conversion of oxidized folate is catalyzed by flavin-dependent enzyme
What are the signs and symptoms of ariboflavinosis?
- Stunted growth
- Lack of energy
- Cheilosis and glossitis
- Angular stomatitis
- Skin lesions/dermatitis (seen with intakes of 0.35mg/1000kcal)
- Corneal vascularization
- Complicated by B6 deficiency (similar symptoms)
- Urinary riboflavin excetion negliginle (reutilization by body)
Explain the FAD Effect
- Used to determine riboflavin status
- EGRAC: Erythrocyte glutathione reductase activity coefficient
- FAD Effect: If activity increases with added FAD, blood is not saturated enough with FAD
- Values: %FAD effect (AC)
→ Adequate: <20% (1-1.20)
→ Marginal: 20-40% (1.20-1.40)
→ Deficient: >40% (>1.40)
-Activity coefficient (AC) = +FAD/-FAD - % Stimulation = (AC*100)-100
- Low glutathione reductase activity may also indicate inadequacy
How can you determine riboflavin status?
- Urinary excretion
- 24-hour excretion of <10% ingested may reflect inadequacy
- Limited accuracy - Serum concentration
- Variable and indicates only current intake - FAD Effect
What are the riboflavin food sources?
- Mainly in coenzyme form (>2/3 as FAD)
- Sources:
→ Dairy and eggs (in US 1/3 of RDA)
→ Meat (liver, kidney)
→ Some green leafy vegetables
→ Enriched flour and breakfast cereals
What is the bioavailability of riboflavin?
- Related to digestibility of food (dairy and meat >plants)
- Impaired by excess alcohol
How is riboflavin excreted?
- Little storage therefore urinary excretion of flavins reflects dietary intake
- Excess riboflavin is rapidly excreted in urine (peak at 2 hours after ingestion)
How is riboflavin stored?
- little storage
- Highest concentrations in liver (1/3 total body flavins, stored as FAD), kidney and heart
