medicine

1. 1
Vitamins and Minerals

2. Vitamins
XIANG ZHUXING

3. Vitamins
 Vitamins are all organic compounds which,
majority cannot be synthesized in the human
body and should be provided in the diet.
 They are essential for the normal processes of
metabolism, including growth and maintenance
of health.
 It is known that the body is able to produce
part vitamins. Example: Vitamin D from
cholesterol and niacin from tryptophan

5. Fat Soluble Vitamins
 Ample reserves of fat soluble vitamins are
stored in the tissues as they are not readily
absorbed from the food.
 With the exception of Vit. K, they do not
serve as coenzymes.
 Indeed Vit D act more like hormone.

6. Structure of Vitamin A
 Vitamin A is a collective term for several related
biologically active molecules.
1. Retinol: alcohol, retinol is found in animal
tissues as a retinyl ester with long-chain FAs
2. Retinal: the aldehyde derived from the
oxidation of retinol.
3. Retinoic acid: the acid derived from the
oxidation of retinal.
4. β-Carotene: plant foods.

8. Vitamin A
 The vitamin A is present in the diet as retinol
(animal source) or as β-carotene (plant
source), some of which is hydrolyzed in the
intestine to form retinal, but the conversion is
inefficient.

9. Vitamin A
Copyright 2005 Wadsworth Group, a division of Thomson Learning

10. Absorption&Transport of Vit A
 Transport to the liver: Retinyl esters present in
the diet are hydrolyzed in the intestinal mucosa,
releasing retinol and FFAs.
 Retinol derived from esters and from the cleavage
and reduction of carotenes is re-esterified to
longchain FAs in the intestinal mucosa and
secreted as a component of chylomicrons into the
lymphatic system.
 Retinyl esters contained in chylomicron remnants
are taken up by, and stored in the liver.

11.  Release from the liver: When needed, retinol is
released from the liver and transported to
extrahepatic tissues by the plasma retinol-binding
protein (RBP).
 The retinol–RBP complex binds to a transport protein
on the surface of the cells of peripheral tissues,
permitting retinol to enter.
 Many tissues contain a cellular retinol-binding protein
that carries retinol to sites in the nucleus where this
vitamin acts in a manner analogous to that of steroid
hormones.
Absorption&Transport of Vit A

12. Mechanism of Action of Vit A
 Retinol is oxidized to retinoic acid, binds with
retinoic acid receptors [RARs]
 The activated retinoic acid–RAR complex binds to
response elements on DNA and regulate retinoid-
specific RNA synthesis, resulting in control of the
production of specific proteins that mediate several
physiologic functions.
 For example, retinoids control the expression of
the gene for keratin in most epithelial tissues of the
body.

14. Functions of Vit A
 Visual cycle: Vitamin A is a component of the visual pigments of rod
and cone cells.
 Rhodopsin, the visual pigment of the rod cells in the retina, consists of
11-cis retinal specifically bound to the protein opsin.
 When rhodopsin is exposed to light, a series of photochemical
isomerizations occurs, which results in the bleaching of the visual
pigment and release of all-trans retinal and opsin.
 This process triggers a nerve impulse that is transmitted by the
optic nerve to the brain. Regeneration of rhodopsin requires
isomerization of all-trans retinal back to 11-cis retinal.
 All-trans retinal, after being released from rhodopsin, is reduced to all-
trans retinol, esterified, and isomerized to 11-cis retinol that is oxidized
to 11-cis retinal.
 The latter combines with opsin to form rhodopsin, thus completing the
cycle. Similar reactions are responsible for color vision in the cone cells.

15.  Maintenance of epithelial cells: Vitamin A is essential for
normal differentiation of epithelial tissues and mucus secretion,
and thus, supports the body’s barrier based defense against
pathogens
 Reproduction: Retinol and retinal are essential for normal
reproduction, supporting spermatogenesis in the male and
preventing fetal resorption in the female.
 Retinoic acid is inactive in maintaining reproduction and in the
visual cycle but promotes growth and differentiation of epithelial
cells. Therefore, animals given vitamin A only as retinoic acid
from birth are blind and sterile.
 β-carotene has an antioxidant role. It plays a protective role
against cancer and cardiovascular disease.
Functions of Vit A

18. Vitamin A
 Source: liver, kidney, cream, butter, and egg
yolk; yellow, orange, and dark green vegs
and fruits.
 The RDA for adults is 900 retinol activity
equivalents (RAEs) for males and 700 RAE
for females.
 In comparison, 1 RAE = 1 μg of retinol, 12 μg
of β-carotene, or 24 μg of other carotenoids

19. Vitamin A in Foods
Adult DRI: 700-900 µg
RAE/day

20. Vitamin A Deficiency
 Night blindness:
 The earliest signs: difficult to see in dim light.
 Prolonged deficiency leads to an irreversible loss in the
number of visual cells.
 Severe deficiency leads to xerophthalmia, a pathologic
dryness of the conjunctiva and cornea, then corneal
ulceration and blindness.
 The condition is most commonly seen in children in
developing tropical countries.

21. Vit A Deficiency
Effect on skin: dryness and roughness of skin
developing keratosis of hair follicles with concomitant
deficiency of Vit-B complex.
Effect on bone and teeth: bone growth is markedly
impaired. Osteoclastic activity is also hampered, causing
defective bone formation.
Effect on general metabolism: Zinc is necessary to
maintain normal plasma concentration of Vit A. This
vitamin is also necessary for the conversion of trioses to
glucose perhaps indirectly through adrenal cortex that
synthesizes hormones concerned with gluconeogenesis

22. Vitamin A Is Toxic in Excess
 Hypervitaminosis A: excessive intake of vitamin A.
Symptoms of toxicity affect:
 the central nervous system (headache, nausea, ataxia, and
anorexia, all associated with increased cerebrospinal fluid
pressure);
 the liver (hepatomegaly with histological changes and
hyperlipidemia);
 calcium homeostasis (thickening of the long bones,
hypercalcemia, and calcification of soft tissues);
 the skin (excessive dryness, desquamation, and alopecia).

23. Clinical Therapeutic Applications
 Dermatologic problems such as acne and
psoriasis are effectively treated with retinoic
acid or its derivatives.
– Tretinoin (all-trans retinoic acid)
– Isotretinoin (13-cis retinoic acid)
 Retinoic acid: acute promyelocytic leukemia.

24. SUMMARY OF
ACTIONS OF
RETINOIDS

25. Vitamin D
 The D vitamins are a group of sterols that have a hormone-
like function.
 The active form is 1,25-dihydroxycholecalciferol(calcitriol).
 Endogenous vitamin precursor: 7-Dehydrocholesterol, an
intermediate in cholesterol synthesis, is converted to
cholecalciferol in the dermis and epidermis of humans
exposed to sunlight.
 Diet: Ergocalciferol (vitamin D2), found in plants, and
cholecalciferol (vitamin D3), found in animal tissues, are
sources of preformed vitamin D activity.They are packaged
into chylomicrons.

26. Metabolism of Vitamin D
•Formation of 1,25-dihydroxycholecalciferol: Vitamin D2
and D3 are converted to the active form by two sequential
hydroxylation reactions.
•Both enzymes are cytochrome P450 (CYP) proteins.
liver kidney

27.  Increased directly by low plasma phosphate
or indirectly by low plasma calcium, which
triggers the secretion of PTH.
 PTH upregulates the 1-hydroxylase.
 Thus, hypocalcemia results in elevated levels
of plasma 1,25-diOH-D3.
 1,25-diOH-D3 inhibits synthesis of PTH,
forming a negative feedback loop. It also
inhibits activity of the 1-hydroxylase.
Regulation of 1-Hydroxylase

29. Function of Vit D
 The overall function of 1,25-
diOH-D3 is to maintain adequate
plasma levels of calcium.
 It performs this function by:
1) Increasing uptake of calcium by the
intestine
2) Minimizing loss of calcium by the
kidney by increasing reabsorption
3) Stimulating resorption
(demineralization) of bone when
blood calcium is low

30. Vitamin D
 Sources: Fish oil, egg yolk, liver are naturally
rich sources of Vit D.
 Milk, unless it is artificially fortified, is not a
good source of vit D.
 The RDA for individuals is 15 micrograms/day

31. Vitamin D in Foods
Adult DRI: 15 µg/day

32. Deficiency
 Vitamin D deficiency causes
a net demineralization of
bone, resulting in rickets in
children and osteomalacia in
adults.
 Rickets is characterized
by the continued formation of
the collagen matrix of bone,
but incomplete mineralization
results in soft, pliable bones.

33. Deficiency
 Osteomalacia
 Demineralization of pre-existing bones
increases their susceptibility to fracture.
 Insufficient exposure to daylight and/or
deficiencies in vitamin D consumption occur
predominantly in infants and the elderly.

34. Deficiency
 Renal osteodystrophy: chronic kidney disease
causes decreased ability to form active vit D
and increased retention of phosphate, resulting
in hyperphosphatemia and hypocalcemia.
 The low blood calcium causes a rise in PTH
and associated bone demineralization with
release of calcium and phosphate.

35. Vit D Toxicity
 Excess vit D level can cause loss of appetite,
nausea, thirst, and stupor.
 Enhanced calcium absorption and bone
resorption results in hypercalcemia, which can
lead to deposition of calcium in many organs,
particularly the arteries and kidneys.
 Toxicity is only seen with use of supplements.

36. Vitamin K
 Vit K exists in several forms: in plants as
phylloquinone (or vit K1),in intestinal bacterial
flora as menaquinone (or vit K2). A synthetic
form, menadione, is able to be converted to K2.
 Functions: It is the only one acting as coenzyme
from the group of fat soluble vitamins.

37. Function of
Vitamin K
Formation of the
functional clotting
factor II,VII, IX, and X
requires the vit K–
dependent
carboxylation of
glutamic acid residues
to γ-carboxyglutamate
(Gla) residues.

38. The Gla residues are good chelators of positively charged calcium ions,
because of their two adjacent, negatively charged carboxylate groups.
This complex binds to negatively charged membrane phospholipids on the
surface of damaged endothelium and platelets, then convert prothrombin to
thrombin followlled by clotting.

40. Vitamin K
 Sources: cabbage, kale, spinach, egg yolk,
and liver.
 There is also extensive synthesis of this
vitamin by the bacteria in the gut.
 RDA:120 micrograms/day for adult males
and 90 micrograms for adult females.

41. Vitamin K in Foods
Adult DRI: 90-120 µg/day

42. Deficiency of Vitamin K
 Unusual, but it is found in patients suffering
from liver diseases (obstructive jaundice), in
new born infants and in patients with
malabsorption.
 It is associated with bleeding disorders.

43. Toxicity of vitamin K
 Prolonged administration of large doses of
synthetic vitamin K (menadione) can produce
hemolytic anemia and jaundice in the infant,
due to toxic effects on the membrane of
RBCs.
 Therefore, it is no longer used to treat
vitamin K deficiency.

44. Vitamin E
 α-tocopherol is the most active form.
 Functions:The primary function of vitamin E
is as an antioxidant in prevention of the
nonenzymic oxidation of cell components
 For example, peroxidation of polyunsaturated
FAs by molecular oxygen and free radicals.

45. Vitamin E
Copyright 2005 Wadsworth Group, a division of Thomson Learning

46. Vitamin E
 Source: vegetable oils (rich sources),nuts,
liver, eggs (moderate amounts)
 The RDA for α-tocopherol is 15 mg/day for
adults.

47. Vitamin E in Foods
Adult DRI: 15 mg/day

48. Deficiency of Vitamin E
 Rare but found in complication of prolonged and
severe steatorrhoea, and of prolonged parenteral
nutrition.
 Deficiency of Vit E causes anemia in children with
cystic fibrosis of pancreas are found to be
tocopherol deficient as a result of steatorrhoea.
 Neurological consequence has also been
described.
 Generally deficiency is investigated by measuring
plasma Vitamin E.

49. Toxicity of Vitamin E
 Vitamin E is the least toxic of the fat-soluble
vitamins, and no toxicity has been observed
at doses of 300 mg/day.

50. Summary

51. Coenzyme Not (except vitK) Yes
Excretion
Less readily excreted,
tend to remain in fat-
storage sites
Kidneys detect and
remove excess in urine

52. Populations consuming diets high
in fruits and vegetables show
decreased incidence of some
chronic diseases.

54. References
 Bender DA: Nutritional Biochemistry of the Vitamins, 2nd ed.
Cambridge University Press, 2003.
 Bender DA, Bender AE: Nutrition: A Reference Handbook.
Oxford University Press, 1997.
 Gibney MJ, Lanham-New S, Cassidy A, et al: Introduction to
Human Nutrition, The Nutrition Society Textbook Series, 2nd
ed. Wiley–Blackwell, 2009.
 Scientific Advisory Committee on Nutrition of the Food
Standards Agency: Folate and Disease Prevention. The
Stationery Office, 2006.
 Institute of Medicine: Dietary Reference Values for Thiamin,
Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12,
Pantothenic Acid, Biotin and Choline. National Academy Press,
2000.
 Geissler C, Powers HJ: Human Nutrition, 12th ed. Elsevier,
2010.