Riboflavin Flashcards
Properties of Riboflavin
- From flavus = yellow and ribose = sugar
- yellow/ orange crystal
- heat stable
- water soluble (reasonably)
- unstable in UV light & alkaline solutions
Structure of riboflavin
- ribityl side chain
- isoalloxazine
structure but not active form
What is the active form of riboflavin?
Active form is a co-factor
* FMN = flavin mononucleotide (riboflavin-5-phosphate) which as an additional phosphate group
* FAD = flavin adenine dinucleotide (riboflavin-5-adenosyl-diphosphate) which the phosphate group like FMN but also an AMP added
How is riboflavin converted to FMN and FAD?
- flavokinase: riboflavin → FMN (needs Zn2+ and an ATP → ADP)
- FAD synthetase: FMN → FAD (needs Mg2+ and an an ATP → PPi)
What regulated flavokinase and FAD synthetase?
conversion of free form to FMN & FAD regulated by thyroid hormone
* ↑ flavokinase activity
* So hypothyroidism would cause a functional deficiency in riboflavin
Mode of action for riboflavin
FMN and FAD can accept 2 H-atoms from substrates (or donate) at the double bonds of the nitrogens.
* cofactor for > 100 flavoproteins
* oxidized = no H+
* reduced = 2 H+
Metabolic role of riboflavin
- Energy production by carrying reducing equivalents into mito. resp. chain (TCA cycle, Electron transport chain, β-oxidation of fatty acids)
- Regulation of redox status
- Detoxification (FMOs)
- Conversion of vitamins (B6 and folate) into their coenzyme form
- Synthesis of niacin (B3) from tryptophan
Role of riboflavin in the CAC
- FAD is a co-factor in the PDH complex (E3)
- FAD is co-factor for succinate dehydrogenase
- ???Also a co-factor for a-ketoglutarate dehydrogenase???
FAD role in PDH
Is a cofactor for E3 subunit (dihydrolipoyl dehdyrogenase) accepting 2 H+ from E2 and donating the 2 H+ to NAD+ (niacin) to form NADH+H
FAD as a co-factor in succinate dehydrogenase
Succinate dehydrogenase is an enzyme in the CAC but it is also complex II in the ETC. so conversion of succinate to fumarate requires FAD to accept 2 H+ to form FADH2. Taking the 2 H+ also means it takes 2 e- so it then transfer the 2e- to an Fe-S cluster which continues down the chain and releases the H+ to become FAD again.
Riboflavin in the ETC
- FAD is co-factor for complex II (succinate dehydrogenase)
- FMN is a co-factor in complex I
FMN role in complex I of the ETC
FMN accepts 2 H+ from NADH+H and 2e- which then passes them on to Fe-S cluster where they continue down the chain and it releases the 2 H+. This complex also pumps H+ the outside
riboflavin role in β-oxidation of fatty acids
FAD is a co-factor for acyl-CoA dehydrogenase, the first step enzyme of β oxidation which oxidizes the fatty acid, reducing FAD to FADH2
riboflavin role in redox status regulation
riboflavin is a co-factor for glutathione reductase so it accepts 2 H+ from NADH+H and then donates the 2 H+ to GSSG to convert it back to GSH
How is riboflavin absorbed?
- Free FMN and FAD from being protein bound via gastric acid and proteases in stomach/intestine
- FMN & FAD are big so broken down the free riboflavin via FMN-phosphatase & FAD-pyrophosphatase
- With low concentration of fiboflavin goes through transporters RFT1&2 but with high concentration some can diffuse.
- In enterocyte some ribofalvin might convert to FAD or FMN but most is transported out to portal vein as free riboflavin or FMN bound to proteins.
- Liver will take some to be used, but otherwise sent to other tissue.
How does riboflavin stay in cells?
present as FAD and FMN in cells and stays within via metabolic trapping
What are the important enzymes to know for absorption?
- proteases
- FMN-phosphatase
- FAD-pyrophosphatase
- RFT 1&2
riboflavin storage
little storage
* highest concentrations in liver (1/3 total body flavins, stored as FAD), kidney & heart
excretion of riboflavin
little storage therefore urinary excretion of flavins reflects dietary intake
* Excess riboflavin is rapidly excreted in urine (peak at 2 hrs after ingestion
Sources of riboflavin
Gut is exposed to flavins from 2 sources
* diet
* bacteria in LI
diet sources of riboflavin
Mainly in coenzyme form (> 2/3 as FAD)
(in US 1⁄3 of RDA)
* dairy and eggs (in USA 1/3 of RDA)
* meat (liver, kidney)
* some green leafy vegetables
* enriched flour & breakfast cereals
bioavailability of riboflavin
related to digestibility of food
* diary & meat > plants
* Impaired by excess alcohol
riboflavin from gut bacteria
- unknown whether this is available to host tissues (Besides colonic epithelial cells)
- synthesis increases with vegetarian diet vs. meat-based diet
riboflavin DRIs
M=1.3 mg/d and F=1.1mg/d
* increases with pregnancy and lactation
* depends on energy intake & other nutrients (including protein)
* UL is not set because no reported cases of riboflavin toxicity (may be due to low solubility & prompt excretion)
measuring riboflavin status
urinary excretion
* 24-hour excretion of <10% ingested may reflect inadequacy
* limited accuracy however
Serum concentration
* variable & indicates only current intake
FAD effect!!
What is the FAD effect used to measure riboflavin status?
Measure enzyme glutathione reductase in RBCs which contains FAD, then add more FAD and if activaty goes up substantially then person is likely deficient
* EGRAC: Erythrocyte glutathione reductase activity coefficient
* FAD effect: If act. ↑ with added FAD, blood is not saturated enough with FAD
What are the EGRAC values?
%FAD effect (AC):
* Adequate: <20%(1-1.20)
* Marginal: 20-40%(1.20-1.40)
* Deficient: >40%(>1.40)
What is a condition wtih riboflavin deficiency?
Ariboflavinosis which is a severe case
* mostly lesions
* Lesions of deficiency seen with intakes of 0.35 mg/1000 kcal
signa and symptoms of ariboflavinosis
- stunte growth
- lack of energy
- cheilosis & glossitis
- angular stomatitis
- skin lesions/ dermatitis
- corneal vascularization
But does ribofalvin deficiency usually mean?
Usually riboflavin deficiency is not by itself and is complicated by B6 deficiency (similar symptoms)
* Urinary riboflavin excretion negligible (reutilization by body)
How is riboflavin associated with iron?
iron absorption & mobilization require reduction of Fe3+ to Fe2+ and flavins are most efficient reductants
How is riboflavin associated with vitamin B6?
enzyme that converts to B6 to active form requires FMN
* may also affect other kinases & phosphatases involved with B6 metabolism
How is riboflavin associated with folate?
final step in conversion of oxidized folate is catalyzed by a flavin-dependent enzyme
populations at risk for riboflavin deficiency
- low intake (elderly and common in countries with less dairy and meat consumptions)
- pregnancy
- disease states (thyroid, diabetes, hyperbilirubinemia)
