1. Micronutrients

2. Vitamins

3. Vitamins
Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans, and therefore must be supplied by the diet. Vitamins are required to perform specific cellular functions. Many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. Only vitamin K of the fat-soluble vitamins has a coenzyme function. Fat soluble vitamins are released, absorbed & transported with the fat of the diet. They are not readily excreted in urine. Significant amounts are stored in the liver & adipose tissue.

4. Vitamins cont. Vitamins are classified into
Water soluble vitamins: Folic
2- Cobalamin
3- Pyridoxine
4- Thiamine
5- Niacin
6- Riboflavin
7- Biotin
8- Pantothenic Acid
9- Ascorbic Acid
Fat soluble vitamins; Vitamin A
2- Vitamin D
3- Vitamin K
4- Vitamin E

5. Water Soluble Vitamins
Some water Soluble vitamins are studied in the current lecture (micronutrients): Thiamine (Vitamin B1) Riboflavin Niacin Pyridixine (Vitamin B6) Other water soluble vitamins: are studied in lectures of the Heme-Immune (HMIM) Block Folic acid Cobalamine (Vitamin B12) Ascorbic acid (vitamin C)

7. Thiamine (Vitamin B1) Sources: Active form of thiamine:
Sources:
Plants: yeast, bran, vegetables and fruits
Animals: liver, kidney, milk & fish.
Active form of thiamine:
Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin B1.
It is formed by the transfer of pyrophosphate group from ATP to thiamine.

9. Thiamine (Vitamin B1) cont.
Functions of TPP:
I- TPP is a coenzyme of oxidative decarboxylation of a- keto acids.
(Mitochondrial Enzymes)
1- The oxidative decarboxylation of pyruvate to acetyl CoA
(Pyruvate dehydrogenase complex)
2- The oxidative decarboxylation of a ketoglutarate to succinyl CoA
in TCA cycle (a ketoglutarate dehydrogenase complex)
  1 & 2 are roles of thiamine in carbohydrate metabolism
3- The oxidative decarboxylation of a -keto acids derived from leucine, valine &
isoleucine (branched chain amino acids catalyzed by a single enzyme complex ,
branched-chain a -keto acids dehydrogenase complex

10. Thiamine (Vitamin B1) cont.
II- Functions of TPP:
TPP acts as a coenzyme of tranketolase enzyme(cytosolic) in the nonoxidative reactions of pentose phosphate pathway
N.B. Thiamine deficiency is diagnosed by an increase in erythrocyte transketolase activity observed on addition of thiamine pyrophosphate (TPP).

11. Thiamine (Vitamin B1) cont.
Clinical indications for thiamine:
The oxidative decarboxylation of pyruvate & a ketoglutarate plays a key role in energy metabolism (especially for carbohydrates) in most cells particularly nervous system tissues (that require continuous supply of sufficient energy).
In thiamine deficiency, the activity of these two dehydrogenase reactions is decreased, resulting in a decreased production of ATP and, thus, impaired cellular functions.

12. Thiamine (Vitamin B1) cont.
Thiamine deficiency diseases:
1-Beriberi: occurs in areas where the main diet is polished rice.
Signs of infantile beriberi:
Tachycardia, vomiting & convulsions
Signs of adult beriberi:
Dry skin, irritability & progressive paralysis (peripheral neuritis).
2-Wernicke-Korskoff syndrome:
Develops in alcoholics due to decreased absorption of the vitamin B1.
Signs: Neuropsychiatric (mainly)
Apathy, loss of memory & rhythmical to- and fro- movements of eyeballs

13. NIACIN Sources: 1- Dietary sources niacin (main source):
1- Dietary sources niacin (main source):
is found in grains & cereals, milk, meat & liver.
2- Tryptophan metabolism:
Limited quantities can be obtained from metabolism of amino acid tryptophan
1 mg of niacin is formed from 60 mg of tryptophan.
This occurs after needs for protein synthesis and energy production.

15. NIACIN cont. Forms of niacin in the body: 1-Niacin (nicotinic acid)
1-Niacin (nicotinic acid)
Available in diet
The active coenzyme forms are nicotinamide adenine dinucleotide (NAD+) & nicotinamide adenine dinucleotide phosphate (NADP+).
2-Nicotinamide
Available in diet.
A derivative of nicotinic acid that contains an amide instead of carboxyl group.
Nicotinamide is readily deaminated in the body & therefore, is nutritionally equivalent to nicotinic acid.
3-NAD+ & NADP+ (coenzymes)
Serve as coenzymes in oxidation-reduction reactions in which the coenzyme undergoes reduction into NADH &
NADPH.

16. NIACIN cont. Clinical indications for niacin: 1-Deficiency of niacin:
causes pellagra,
involving the skin, GIT and CNS
Manifestations: THREE Ds : Dermatitis, Diarrhea, Dementia (Death, if untreated)
2-Treatment of hyperlipidemia:
Niacin (at a dose of 1.5 g/day or ~ 100 times the RDA) strongly inhibits lipolysis in adipose tissue, the primary producer of circulating free fatty acid.
The liver normally uses these circulating fatty acids as a major precursor for triacylglycerol synthesis.
Thus, niacin causes a decrease in triacylglycerol synthesis, required for synthesis of production of VLDL. LDL is derived from VLDL in the plasma. Thus, VLDL & LDL are lowered.
Therefore, niacin is particularly useful in the treatment of type IIb hyperlipoproteinemia, in which VLDL & LDL are elevated.

17. Riboflavin (Vitamin B2)
Sources:
Plants: yeast and vegetables
Animals: liver, eggs & milk
Active forms of riboflavin:
1-Flavin mononucleotide (FMN)
2-Flavin adenine dinucleotide (FAD)

18. Riboflavin (Vitamin B2) cont.
Functions:
 FMN & FAD are coenzymes for many enzymes used for different metabolic pathways.
FMN & FAD are each capable of reversibly accepting two hydrogen atoms, forming FMNH2 or FADH2
Riboflavin deficiency:
Riboflavin deficiency is not associated with major human disease.
Symptoms: include: dermatitis, cheliosis (fissuring at the corners of mouth) and glossitis (smooth and purplish tongue)

19. Pyrodoxine (VITAMIN B6)
Vitamin B6 is a collective term of pyridoxine, pyridoxal & pyridoxamine, all derivatives of pyridine & differs only in the nature of the functional group attached to the ring.
Sources:
Pyrodoxine occurs primarily in plants
Pyridoxal & pyridoxamine are found in foods obtained from animals.
The active form:
All three compounds can serve as precursors of the biologically active coenzyme pyridoxal phosphate (PLP).

21. Pyrodoxine (VITAMIN B6) cont.
Functions of pyridoxal phosphate (PLP):
PLP acts as a coenzyme for a large number of enzymes, especially those involved in amino acid metabolism.
1-Transamination:
Aspartate Tansaminase (AST)
Oxalactetate Glutamate Aspartate a ketoglutarate
  PLP
Alanine Tansaminase (ALT)
Pyruvate + Glutamate Alanine a ketoglutarate
PLP
Transamination is an essential component of disposal of amino group in amino acid metabolism

22. Pyrodoxine (VITAMIN B6) cont.
2-Deamination :
Serine Pyruvate + NH3   
3-Decarboxylation of amino acids:
Histidine Histamine + CO2
  (histamine is required in allergic reactions)
Glutamic acid GABA CO2
  (GABA is a neurotransmitter in CNS)
4-Condensation: Glycine + Succinyl CoA d aminolevulinic acid
First step in heme synthesis in erythrocyte producing
cells in bone marrow

23. Pyrodoxine (VITAMIN B6) cont.
5- for disposal of homocysteine:
Homocysteine is produced from metabolism of amino acid methionine
Then, it is metabolized into amino acid cysteine by:
Cystathionine Synthase
PLP (B6)
Homocysteine + Serine Cystathionine
Cystathionase
Cystathionine cysteine a-ketobutyrate NH3
N.B: The other pathway for homocysteine is conversion to methionine by homocysteine methyltransferase (coenzyme: methylcobalamin, B12)
Defect in homocysteine metabolism leads to accumulation of homocysteine that predisposes in atherosclerosis

24. Pyrodoxine (VITAMIN B6) cont.
Clinical indications for pyridoxine:
Isoniazid (izonicotinic acid hydrazide)
An anti-tuberculous drug that can bind with PLP forming an inactive
derivative, leading to vitamin B6 deficiency
Accordingly, B6 should be supplied with isoniazid treatment.
Dietary deficiency of pyridoxine are rare but seen in:
New born infants fed formulas low in B6.
Women taking oral contraceptives
Alcoholics
Toxicity of pyridoxine is manifested by neurological symptoms at intakes more than 2 g/day.

25. Fat Soluble Vitamins Vitamin A: is studied in the CNS Block
Vitamin D: is studied in Endocrine , Urinary & Musculoskeletal Blocks
Vitamin K : is studied in the Heme-Immune Block
Vitamin E: is studied in the current lecture (GIT Block)

26. Vitamin E
E vitamins consist of 8 naturally occurring tocopherols, of which - tocopherol is the most active.
The primary function of vitamin E is an antioxidant in prevention of the nonenzymic oxidation of cell components as polyunsaturated fatty acids by molecular O2 & free radicals.

27. Vitamin E Distribution & requirements of vitamin E:
Vegetable oils are rich sources (plant sources)
Liver & eggs contain moderate amounts (animal sources)
RDA for a-tocopherol is mg for men
8 mg for women
Requirement is increased with increased intake of polyunsaturated fatty acids.

28. Vitamin E cont. Deficiency of vitamin E
Deficiency of vitamin E is almost entirely restricted to premature infants.
In adults, it is usually associated with defective lipid absorption or transport.
Signs of vitamin E deficiency include sensitivity of RBCs to peroxide & appearance of abnormal cellular membrane.

29. Vitamin E cont. Clinical indications
Vitamin E is not recommended for the prevention of chronic disease,
such as coronary heart disease or cancer.
Subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention
Study trial who received high doses of vitamin E, not only lack
cardiovascular benefit but also had an increased incidence of stroke.
Toxicity of vitamin E: no toxicity at 300mg / day dose

30. Minerals & Trace Elements
Macrominerals (needed in quantities more than 100 mg/day)
calcium, phosphorous, sodium , potassium, chloride, magnesium
Calcium & phosphorous: in ENDO Block
Sodium, potassium & chloride: in Urinary Block
Microminerals (needed in quantities less than 100 mg/day)
1- Trace elements (needed in amounts of mgs)
iron, iodine, copper, zinc, cobalt
Iron: in HMIM Block
Iodine: ENDO Block
2- Ultraelement (needed in amounts less than mg)
as manganese, selenium , fluoride, chromium

31. Magnesium It is the second most abundant intracellular cation.
It is essential for the activity of many enzymes.
Bone contains about 50 % of the body’s magnesium.
Dietary intake of magnesium is normally about 250 mg/ day
When dietary intake is restricted, renal conservation mechanism are
normally so efficient that depletion, if develops at all, comes on very
slowly.

32. Magnesium cont. Magnesium deficiency
Rarely occurs isolated but usually accompanies deficiency of potassium,
calcium and phosphates
Manifested by muscle weakness, sometimes accompanied by tetany, cardiac
arrythmias and CNS abnormalities (convulsions)
Hypermagnesemia
Most often due to acute renal failure or the advanced stage of chronic
renal failure

33. Copper
It is a major component of enzymes involved in redox reactions , like
superoxide dismutase, cytochrome C oxidase
In plasma copper is bound mainly to ceruloplasmin (mainly in addition to
small fraction bound to albumin)
Deficiency is uncommon and usually occurs with malunutrition and
malabsorption
Manifested by: microcytic hypochromic anemia
low concentrations of ceruoloplasmin

34. Copper cont. Menkes’ syndrome:
a recessive X-linked genetic defect in copper transport and storage, where
there is defect in transport of copper from mucosal cell, leading to mental
deterioration, failure to thrive, diminished activities of copper containing
enzymes.
Wilson’s disease (hepatolenticular degeneration):
is associated with copper accumulation in liver (cirrhosis) & brain
Copper may deposit in cornea (Kayser- Fleischer rings)
There is plasma low level of ceruloplasmin & copper
and increased urinary copper excretion

35. Zinc It is the most abundant trace element next to iron
Rich sources of zinc include meat , fish, and dairy products.
Typical diet supply mg of zinc/day
The body does not store zinc, the main route for excretion is through the gut
Along with magensium , zinc is the most frequently encountered metal cofactor for enzyme activity, where it mainly serves as integral part of the active site
PBG synthase and carbonic anhydrase alkaline phosphatase are among the enzymes which need Zn

36. Zinc (cont.)
Zinc enzymes are essential for growth, wound healing , integrity of C.T., reproductive function , the immune system
DNA and RNA polymerases require zinc to maintain the structure conformation of DNA
Symptoms of zinc deficiency
include growth retardation, skin lesions, slow wound healing, impotence,
dwarfism , loss of body hair
Causes of zinc deficiency:
- Insufficient dietary zinc (major cause)
- Pregnancy ,lactation , old age
- Administration of metal chelating agents, diuretics , anti –cancer drugs
- Gastrointestinal malabsorption syndromes
- patients receiving total parenteral nutrition

37. Selenium
Selenium is a component of glutathione peroxidase , which has anti-oxidant function .
It is also part of iodothyronine deiodinase enzyme essential for formation of T3
Selenium deficiency has been associated with cardiomayopathy and selected muscle weakness, osteoarthritis and increase incidence of cancer