Nutritional Disorders: Vitamins C, B2, B3, B5, & B7
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water-soluble vitamin deficiencies
Overview
- Vitamin C (ascorbic acid) deficiency causes scurvy.
- Vitamin B2 (riboflavin) deficiency causes angular stomatitis.
- Vitamin B3 (niacin) deficiency causes pellagra.
- Vitamin B5 (pantothenic acid) deficiency is a rare deficiency.
- Vitamin B7 (biotin) deficiency results most notably from raw egg white consumption.
vitamin C (ascorbic acid)
Source
- Indicate that it's found in fruits and vegetables.
Biochemistry
- Indicate that it serves as an antioxidant (it inactivates hydroxyl free radicals).
- For reference, remind ourselves of the chemistry acronym: OIL RIG
- Oxidation is Loss (of electrons)
- Reduction is Gain (of electrons)
Vitamin C reduces iron and copper in two key separate reactions that we'll explore, now.
- In collagen synthesis, it plays an important role in the hydroxylation of proline and lysine residues, specifically in the reduction of iron.
Proline Hydroxylation
Let's walk through this biochemistry with proline as an example.
- Indicate a prolyl residue.
- Then, show that prolyl hydroxylase (a dioxygenase) requires iron (Fe2+) to activate oxygen and form 4-hydroxyproline.
- In the process, the iron is oxidized to Fe3+.
- Show that vitamin C is necessary to reduce the iron back to Fe2+, thus serving as an antioxidant.
- A parallel reaction exists for lysine, as well.
Norepinephrine synthesis
Next, consider the role of vitamin C in norepinephrine synthesis.
- Dopamine beta-hydroxylase hydroxylates dopamine to norepinephrine.
- In the process, it oxidizes copper (Cu+) to Cu2+.
- Indicate that vitamin C is necessary to reduce it, again, serving as an antioxidant.
Scurvy
- Indicate that the primary clinical presentation of vitamin C deficiency is scurvy, which presents with, notably:
- Bleeding gums from blood-vessel fragility, along with ecchymoses and subperiosteal hemorrhages
- Additional skin lesions
- Periodontal disease
- Characteristic keratotic plugging of hair (called "corkscrew hairs").
vitamin B2 (riboflavin)
Key source
- Dairy products
Biochemistry
- Indicate that it comprises the reactive moieties for flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are key cofactors in major redox reactions.
- Remind ourselves that B2 is Riboflavin, which will help us remember the names of these moieties.
- Both FAD and FMN pick up 2 (two) electrons, which we can remember because riboflavin is vitamin B2 (two).
Clinical Presentation
- Now, indicate that B2 deficiency results, most notably, with angular stomatitis (aka angular cheilitis, cheilosis).
- Draw a mouth and indicate that the pathology occurs at the corners of the mouth where there's a whitening/pallor with cracking/fissuring.
- As well, B2 deficiency tends to cause a seborrheic dermatitis.
vitamin B3 (niacin)
Source
- To begin, indicate that we obtain it from meat, grains, cereals, and eggs (as examples) but that it does not meet the strict definition of a vitamin because it is synthesized from tryptophan.
- We can remember this when we consider tryptophan's R group is a ring-containing structure, which we show now.
Biochemistry
- This ring structure leads us to the key aspect of niacin – the nicotinamide ring that it provides both nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
- They inherit a positively charged nitrogen that confers especially good properties for redox reactions: they exist in oxidized forms as NAD+ and NADP+ and reduced forms as NADH and NADPH.
Niacin in the Treatment of Dyslipidemia
- Now, indicate that niacin is used to treat dyslipidemia – it lowers VLDL and raises HDL; aspirin is given 30 minutes prior to administration to avoid flushing.
Niacin Deficiency (Pellagra)
- Next, indicate that niacin deficiency causes, most notably, pellagra, which we remember as the 3 D's of vitamin B3 (three):
- Diarrhea
- Dementia with hallucinations
- Dermatitis that is photosensitive with a characteristic dermatomal rash at C3/C4.
- Consider that a common pathogenesis for pellagra is low tryptophan, which can occur with:
- Corn-based diets (low-tryptophan, difficult to absorb niacin content)
- Hartnup disease, an autosomal recessive disorder that causes defective intestinal (enterocyte)
- Carcinoid syndrome, in which liver tumor enterochromaffin cell metastasis causes overproduction of 5-hydroxytryptamine, which hypermetabolizes tryptophan – thus, tryptophan is diverted from NAD production, causing pellagra.
Vitamin B5 (pantothenic acid)
- Vitamin B5 (pantothenic acid) is an essential component of coenzyme A and the fatty acid synthase complex.
- Although it's named "pantothenic" acid, we think of it as "pento-" for "five" to try to remember that pantothenic acid is vitamin B5.
vitamin B7 (biotin)
Biotin Biochemistry
- Now, add vitamin B7 (biotin), which is a key cofactor for carboxylation enzymes, which add a 1-carbon group.
- For reference, key carboxylation reactions are:
- Pyruvate (3C) to oxaloacetate (4C).
- Acetyl-CoA (2C) to malonyl-CoA (3C)
- Propionyl-CoA (3C) to methylmalonyl-CoA (4C).?
Source
- Show that it originates from bacteria in the intestine.
Biotin Deficiency
- Indicate that this rare deficiency syndrome causes dermatitis, enteritis, and alopecia.
- A key cause is prolonged consumption of raw egg whites (because egg whites avidly bind biotin).
- Alternatively, indicate that failure to supplement parenteral nutrition with biotin in patients with short bowel syndrome will also cause biotin deficiency because, again, biotin originates from bacterial synthesis in the intestine.