Riboflavin (3 questions) Flashcards
What is the oxidized CoE. form of riboflavin?
FAD
What is the reduced Co.E form of riboflavin?
FADH
What are the 2 CoE. forms of riboflavin?
FMN and FAD/FADH
RDAs for riboflavin
Males have a slightly HIGHER RDA, starting at ages 14 and up
What are the best food sources of riboflavin?
Eggs, kidneys and liver, lean meats, and milk products, green vegetables
Fortified grains and cereals
What form is riboflavin in most foods?
FAD
What is the form of riboflavin in eggs and milk?
Free riboflavin
Similar to XXXXX, riboflavin is soluble in water, meaning….
THIAMIN; about twice as much riboflavin content is lost in cooking water when foods are boiled, and unless the liquid is added back, riboflavin will be lost.
Flavokinase
Enzyme converting natural riboflavin —> FMN CoE. form; in the enterocyte
FAD Synthetase
Enzyme converting FMN —> FAD
Negative FB here
Unregulated in times of growth
How is riboflavin absorbed?
Since it is protein-bound in food, HCl acid and proteases (secreted in the stomach, pancreas, S.I.) cleave off the non-covalent bond.
FMN
Riboflavin + phosphate group
FAD
Riboflavin + Pyrophosphate + AMP (Adenine Monophosphate group)
Main CoE. form; oxidized form
FAD pyrophosphatase
Enzyme secreted from stomach, pancreas, S.I that is required for cleaving the covalent bond for absorption of riboflavin
FAD ———————> FMN
FAD pyrophastase- cleaves off AMP portion
FMN phosphatase
For riboflavin absorption
FMN ———————–> Free Riboflavin
FMN phosphatase- cleaves off final phosphate group
How is riboflavin absorbed?
It must be in the free riboflavin form, then it will be absorbed in the proximal S.I and COLON, via RFVT3
RFVT3
Riboflavin Vitamin Transporter, located in proximal SI and colon
depends on H+ that will be pumped into the enterocytes along with riboflavin
(T/F) Riboflavin has poor bioavailability.
FALSE; 95% of riboflavin from food is absorbed, up to 25 mg
What happens once riboflavin enters the enterocyte?
Hint: there are two options
- Free riboflavin can leave the enterocytes and go into portal circulation by way of RIBOFLAVIN VITAMIN TRANSPORT 1 OR 2
OR
- Free riboflavin can be converted to FMN via FLAVOKINASE (ATP-dependent), then FMN can be converted to FAD via FAD SYNTHETASE (ATP-dependent).
—–FAD trapped inside the enterocyte is going to be used by the mito. for some of those redux reactions that are similar to niacin and NADH. More later!!!!
How is riboflavin transported in the blood?
~50% free riboflavin
~10% FMN
~40% FAD
Where is the majority of riboflavin stored?
Liver, kidneys, heart have the greatest concentrations
What is the major riboflavin form that is stored in cells? What percentage?
FMN, ~60-90% in cells
FAD is secondary in cells, ~5-20%
The body stores enough riboflavin to meet its need for how long?
2-6 weeks in a normal adult.
Note this will vary on activity level, gender, weight
Explain how intracellular conversion of FMN to FAD is controlled.
End-product inhibiting FAD synthetase enzyme
What accelerates or upregulates the conversion of riboflavin into it’s coenzyme forms?
ACTH, aldosterone, and thyroid hormones
Remember, in times of growth the enzymes are upregulated driving the expression of FAD synthetase
What are the general functions of CoE’s of riboflavin?
- ETC (FADH2 to FAD; dropping off 2 electrons at Complex II)
- Folate metabolism (FADH2 provides 2 H+ in the conversion of 5,10-methylene THF to 5-methyl THF)
- FMN (required for pyridoxamine oxidase (which converts PMP and PNP to PLP)
- Glucose Metabolism (FAD is required for conversion of pyruvate to acetyl-CoA)
- FA Metabolism (FAD is required for acyl-CoA dehydrogenase in beta-oxidation)
- Antioxidant System (FAD is required for glutathione reductase)
What riboflavin CoE plays a role in the ETC? What does it do?
FADH (reduced form) at Complex II, drops off its 2 electrons, which will be passed down the ETC. The electrons being pumped into the intracellular space builds the IONIC GRADIENT, which is used to power ATP Synthase, producing ATP.
What riboflavin CoE. plays an important role in folate metabolism? What does it do?
FADH2 provides two H+ in the conversion of 5,10-methylene THF to 5-methyl THF
FADH2 ((and NADPH)) will act as reducing agents, so they become oxidized, so FAD and NADP are going to be released from this reaction.
What riboflavin CoE. plays an important role in vitamin B6 metabolism?
FMN
it is a CoE. for PYRIDOXAMINE OXIDASE ((which drives the reaction toward the formation of PLP (remember??). So PMP and PNP are going to be converted to PLP.
How is riboflavin involved with glucose metabolism?
FAD serves as an intermediate electron carrier (along with NADH), being able to pass on electrons and helping with the oxidative decarboxylation of PYRUVATE —-> ACETYL-CoA
What riboflavin CoE. form has an important role in FA metabolism? What does it do?
FAD is a coenzyme for Acyl CoA dehydrogenase (used in the first step of beta-oxidation). FAD is reduced to FADH2, which will go on to ETC to generate ATP (in Complex II).
Which riboflavin CoE. participates in the indigenous antioxidant system?
FAD functions as a CoE. for GLUTATHIONE REDUCTASE, so that when NADPH transfers, it’s electrons over to FAD, it’s going to be reduced to FADH, and glutathione reductase is going to transfer those 2 electrons to glutathione, thus changing oxidized glutathione to the reduced glutathione form.
From there, the reduced glutathione can participate in these antioxidant activities, so that glutathione peroxidase is going to take the reduced glutathione and transfer the electrons to pro-oxidant compounds, such as hydrogen peroxide, and neutralize those by converting it to water.
Riboflavin deficiency
Ariboflavinosis, rarely occurs in isolation.
Characterized by:
——Chelosis (painful lesions on the outside of the lips)
——Glossitis
——-Swollen oral cavity
((Similar to niacin, epithelial cells are affected, specifically in the oral cavity)
(T/F) Although not due to a deficiency, mutations in genes of enzymes that require coenzyme forms of riboflavin can effect the binding of FMN/FAD to the enzyme; therefore, impair the biochemical reactions.
TRUE; in some cases, pharmacological doses (up to 200 mg/day) of riboflavin may be beneficial for those with these gene mutations.
What is the upper tolerable limit for riboflavin?
None has been established
What is the most sensitive method for determining riboflavin status?
HINT: this is done in a research setting
Measure the activity of the FAD-dependent enzyme ERYTHROCYTE GLUTATHIONE REDUCTASE
This allows us to view riboflavin status in isolation.
Clinically, MDs would order a panel to look at water-soluble vitamin status since deficiencies are not seen in isolation.
