Micronutrients in Health and Disease

Question 1

Vitamins definition

Answer 1

Organic compounds required for normal metabolic function, which cannot be synthesised by the body

• Deficiency results in disease (treated by restoring levels)
• only require small amounts (ug-mg)

Question 2

Minerals definition

Answer 2

Inorganic elements which have physiological function

• required in varying amounts from ug (‘trace elements’) to g (Na, Ca)
• the Reference Nutrient Intake (RNI is sufficient for 97.5% of population (Still not met across UK)

Question 3

Vitamin types/examples

Answer 3

Water soluble
- Vitamins B and C

Fat soluble
- Vitamins E, K, A and D

Question 4

Fortified foods

Answer 4

Legal requirement to be fortified with vitamins/minerals

• margarine - Vitamins A and D
• White flour - Iron, Niacin, thiamin and calcium

Question 5

Vitamin roles: Coenzymes

Examples

Answer 5

Conversion into coenzymes

• Thiamine (B1) in link reaction + Krebs cycle (deficiency = Beri-Beri disease, muscle wekaness…)
• Riboflavin (B2) for FAD in metabolism
• Niacin (B3) for NADH (deficiency = pellagra)
• Folic Acid (B9) in DNA synthesis
• Vitamin K for blood clotting

Question 6

Vitamin roles: tissue-specific regulation

Examples

Answer 6

• Vitamin A in Vision (red cell function)
• Vitamin C in Collagen synthesis
• Vitamin D in bone formation/maintenance

Question 7

Niacin

Answer 7

A cofactor (constituent of NAD[P]H) that doesn’t follow original vitamin definition:

• can be synthesised in the body from tryptophan
• ‘vitamin’ status determined by existence of a deficiency state (Pellagra)

Question 8

Niacin Deficiency: Pellagra

Answer 8

Also due to tryptophan deficiency, is characterised by the 4 D’s:

1) Dermatitis (sunburn-like rash)
2) Diarrhoea
3) Depressive psychosis
4) Death

Often associated with corn/maize based diets where niacin isn’t bioavailable (except in Mexico…)

Common in refugee camps and in developed world associated with alcohol/medication abuse

Question 9

Niacin Synthesis

Answer 9

Produced from Tryptophan which produces a number of chemical compounds in its metabolic pathway:

1) Seretonin & Melatonin (deficiency = depression/anxiety)
2) Kyneurinic Acid (at low levels causes anxiety)
3) Picolinic Acid (lack of this underpins skin photosensitivity)
4) Quinolinic Acid (NAD precursor)

Question 10

Vitamin B6

Answer 10

a. k.a. Pyridoxine, required for metabolism and is a precursor for Pyridoxal Phosphate (PLP), an important cofactor required for ~150 enzyme’s activity
- PLP binds the amino acid to form a Schiff Base which has several different possible fates depending on which group is broken (remove R, Amine or Carboxy groups)

B6 = important in haem synthesis, neurotransmitter synthesis and modulating Steroid hormones by competitively inhibiting their receptors

Question 11

Vitamin B6 deficiency/excess intake

Answer 11

Severe deficiency is uncommon but inadequate intake is common

Excess intake = permanent nerve damage

Question 12

Vitamin B12

Answer 12

Large complex molecule containing Cobalt (III) ion, similar to heme
- Only found in animal-based food sources (vegans need supplements!)

Required for 2 enzyme reactions:

1) Methionine Synthase
- Methionine synthase and DNA methylation reactions

2) L-methylmalonyl-CoA mutase
- Involved in breakdown of fatty acids with odd numbers of C atoms

Question 13

Vitamin B12 absorption and transport

Answer 13

1) Bound in the stomach to haptocorrin to transport to the duodenum
2) In duodenum the haptocorrin is degraded allowing B12 to bind to Intrinsic Factor
3) B12-Intrinsic Factor complex is absorbed into small intestine via CUBAM receptor
4) Transported to the blood via the ABC transporter MRP1

Question 14

Causes of B12 deficiency

Answer 14

1) Dietary deficiency (vegans and veggies common)

2) Autoimmune pernicious anaemia
- Antibodies attack the Intrinsic factor or pancreatic cells which produce it (people unable to absorb B12)

3) Acid Blocking drugs (e.g. Proton pump inhibitors) taken for indigestion result in a lack of stomach acid and therefore reduced B12 absorption
4) Pancreatitis reduces absorption (as does Crohn’s etc…)

Question 15

Effects of B12 deficiency

potential explanation of symptoms

Answer 15

Causes Megaloblastic anaemia
- large (macrocytic), structurally abnormal immature erythrocytes (observed in peripheral blood smears)

Causes serious neurological symptoms

• Common: numbness and peripheral tingling
• If untreated: limb weakness, poor coordination, altered gait, eventual death

Reasons for symptoms unclear:

• abnormal myelin synthesis due to disruption of odd-chain fatty acid metabolism
• Affecting cytokines and growth factors in nervous system

Question 16

Importance of Folate (B9)

Answer 16

Vital for DNA synthesis
- facilitates the essential carbon transfer needed for the biosynthesis of serine, methionine, glycine, choline, purine nucleotides and dTMP (dUMP –> dTMP –> DNA)

Question 17

Folate regeneration pathway

Answer 17

dUMP –> dTMP (thymidylate synthase)

Targeted for antibiotic and cancer therapy

• FdUMP = irreversible inhibitor
• Methotrexate & aminopterin = anticancer and immunosuppressant
• Trimethoprin = antibiotic that binds bacterial DiHydroFolate Reductase (DHFR) tighter than mammalian

Question 18

Loss of Folate regeneration causing deficiency

Answer 18

Results in Neural tube defects in 1/1000 babies in the UK (it’s common in pregnant women)

• Folate supplements advised for pregnant women in UK
• USA, Canada and Australia enforce mandatory fortification of flour with folic acid
  » BUT, risks hiding the symptoms of B12 deficiency which is essential for folate recycling (causes accumulation of unusable 5-methyl TH4-)

Diminished folate levels have been implicated in several types of cancer
- but some studies suggest excess folate can cause cancer too

Question 19

Vitamin C (Ascorbic Acid)

Answer 19

Required as a coenzyme for prolyl hydroxylase and lysyl hydroxylase during collagen synthesis

• also involved in bile acid and adrenalin synthesis
• has antioxidant properties

Question 20

Collagen

Answer 20

Fundamental structural protein found in almost all tissues

• fibrous, insoluble, high tensile strength, highly abundant
• synthesised as a triple helix: stabilised by covalent cross-links

Question 21

Role of Vitamin C in collagen synthesis

Answer 21

• Hydroxyproline involved in H bond formation helps stabilise triple helix
• Hydroxylysine residues are attachment sites for sugar residues involved in cross-linking

Insufficient Vitamin C = inhibited collagen synthesis = scurvy

Question 22

Scurvy

Answer 22

Lack of collagen in cells/tissue

• leads to fatigue, joint pain, muscle weakness, poor healing, gum disease
• if untreated becomes fatal: bleeding heart muscle