Download 3 .Micronutrients GIT

Micronutrients
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.
Vitamins are classified into
Water soluble vitamins: 123456789Fat soluble vitamins;
Folic
Cobalamin
Pyridoxine
Thiamine
Niacin
Riboflavin
Biotin
Pantothenic Acid
Ascorbic Acid
1- Vitamin A
2- Vitamin D
3- Vitamin K
4- Vitamin E
Water Soluble Vitamins
Some water Soluble vitamins
are studied in the current lecture (micronutrients):
Thiamine (Vitamin B1)
Riboflavin
Niacin
Pyridoxine (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)
Thiamine (Vitamin B1)
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.
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.
II- 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).
Clinical indications for thiamine:
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
NIACIN
Sources:
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.
Forms of niacin in the body:
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.
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.
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)
Functions:
FMN & FAD are coenzymes for many enzymes used for different metabolic
pathways for energy metabolism.
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)
Pyridoxine (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).
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: Transfer of amino group from amino acid to keto acid
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
2-Deamination : removal of amino group in the form of amonia
Serine
Pyruvate + NH3
3-Decarboxylation of amino acids:
Histidine
Glutamic acid
4-Condensation:
Histamine + CO2
(histamine is required in allergic reactions)
GABA + CO2
(GABA is a neurotransmitter in CNS)
Glycine + Succinyl CoA
d aminolevulinic acid
First step in heme synthesis in erythrocyte producing
cells in bone marrow
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
Cystathioninase PLP (B6)
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
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.
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)
Vitamin E
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E vitamins consist of 8 naturally occurring tocopherols, of which a- 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.
Distribution & requirements of vitamin E:
• Vegetable oils are rich sources
(plant sources)
• Liver & eggs contain moderate amounts (animal sources)
• RDA for a-tocopherol is
10 mg for men
8 mg for women
• Requirement is increased with increased intake of polyunsaturated fatty acids.
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
(haemolytic anemia) & appearance of abnormal cellular membrane (cellular
degeneration).
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 and cancer?.
Toxicity of vitamin E: no toxicity at 300mg / day dose
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- Ultra trace elements (needed in amounts less than mg)
as manganese, selenium , fluoride, chromium
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.
• 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
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
• 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
Zinc
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It is the most abundant trace element next to iron
Rich sources of zinc include meat , fish, and dairy products.
Typical diet supply 10-15 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, carbonic anhydrase and alkaline phosphatase are among the
enzymes which need Zn
• Metabolic indications of zinc
• 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
Selenium
• Selenium is a component of glutathione peroxidase , which has antioxidant 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