1. 22-04-2018
Vitamins & minerals
TONY SCARIA 2010
KMC
Vitamins
A vitamin is defined as an organic compound that is required in the diet in small amounts
for the maintenance of normal metabolic integrity.
However, vitamin D, which is formed in the skin from 7-dehydrocholesterol on exposure to
sunlight, and niacin, which can be formed from the essential amino acid tryptophan, do
not strictly comply with this definition
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Vitamins produced by intestinal bacteria
• Riboflavin
• Biotin
• Pantothenic acid
• Vitamin K
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vitamins depleted in antconvulsant therapy
• folic acid
• vitamin D
• vitamin B6(pyridoxine)
• vitamin k
• fits drugs prevent koagulation
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Vitamins synthesised by intestinal bacteria
• only three vit.,
• vit K
• Biotin
• vit B12
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Thaimine (vitamin B1)
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• Vitamin B1 (thiamine) contains two heterocyclic rings—a pyrimidine
ring and a thiazole ring which are joined by a methylene group.
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• FOOD SOURCES
• 2 mg/d.
• yeast, pork, legumes, beef, whole grains, and nuts.
• Milled and polished rice contain little thiamine, if any.
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Thiazolium ring functional part of TPP
The active form of vitamin B1 is thiamine diphosphate(TPP),
which contributes as a coenzyme to the transfer of hydroxy
alkyl residues (active aldehyde groups).
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• Thiamine
• Thiamine requirement increase in intake of excess carbohydrates
• Coenzyme for enzymes involved in carbohydrate metabolism
• Decreased intake of thiamine decreased energy production
• beri beri is manifested when diet is rich in carbohydrate & deficient in thiamine
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Thiamine deficiency
• more common
• in cultures that rely heavily on a rice-based diet.
• Tea, coffee) (caffeinated and decaffeinated), raw fish, and shellfish
• contain thiamineases, which can destroy the vitamin. Thus, drinking large amounts of tea
or coffee can theoretically lower thiamine body stores.
• Alcoholics
• c/c peritoneal dialysis
• Hemodialysis
• Reffeding after starvation
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• DEFICIENCY
• causes
• alcoholism and
• Alcohol is known to interfere directly with the absorption of thiamine and with the
synthesis of thiamine pyrophosphate.
• Thiamine should always be replenished when refeeding a patient with alcoholism, as
carbohydrate repletion without adequate thiamine can precipitate acute thiamine
deficiency.
• chronic illness, such as cancer.
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• Wet beriberi
• cardiovascular symptoms
• due to impaired myocardial energy metabolism and dysautonomia, and can occur after
3 months of a thiaminedeficient diet.
• enlarged heart, tachycardia, high-output congestive heart failure, peripheral edema, and
peripheral neuritis.
• dry beriberi
• symmetric peripheral neuropathy of the motor and sensory systems with
diminished reflexes.
• The neuropathy affects the legs most markedly, and patients have difficulty
rising from a squatting position.
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• Accumalation of lactate vasodilation high output cardiac failure
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Alcoholic patients with chronic thiamine
deficiency
• Wernicke’s enceph alopathy,
• horizontal nystagmus,
• ophthalmoplegia (due to weakness of one or more extraocular muscles),
• cerebellar ataxia, and
• mental impairment.
• Wernicke-Korsakoff syndrome
• additional loss of memory and a confabulatory psychosis
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diagnosis
• functional enzymatic assay of RBC transketolase activity
• measured before and after the addition of thiamine pyrophosphate.
• A 25% stimulation by the addition of thiamine pyrophosphate (an activity coefficient of
1.25) is taken as abnormal.
• Blood lactate is elevated
• Thiamine or the phosphorylated esters of thiamine
• be measured by high-performance liquid chromatography (HPLC)to detect
deficiency.
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TREATMENT
a. In acute thiamine deficiency with either cardiovascular or neurologic signs, 100 mg/d of thiamine should be given parenterally for 7
days, followed by 10 mg/d orally until there is complete recovery.
b. Cardiovascular improvement occurs in 12 h, and ophthalmoplegic improvement occurs within 24 h.
c. Other manifestations gradually clear, although psychosis in the Wernicke-Korsakoff syndrome may be permanent or persist for
several months.
TOXICITY
a. Although anaphylaxis has been reported after high doses of thiamine, no adverse effects have been recorded from either food or
supplements at high doses. Thiamine supplements may be bought over the counter in doses of up to 50 mg/d.
b. Transketolase activity in blood (RBCs) is the best method to detect thiamine deficiency
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Hartnup ds pellagra like symptoms (d/t lack of
tryptophan availability for niacin biosynthesis
d/t defect in membrane transport mechanism of monoamino mono carboxylic aa such as tryptophan
by SI mucosa & proximal renal tubule
Indole derivative of unabsorbed tryptophan formed by intestinal bacteria
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• Hartnup disease is diagnosed by obermayer test
• Detects indole ring in urine
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Pellagra d/t deficiency of niacin
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B6 deficiency hormone dependant cancer
• Vit. B6 →important in steroid hormone ac on →
• i.e. terminate the action of hormones
• PLP removes receptor – hormone complex from DNA
• therefore its deficiency causes led increased sensitivity to steroid hormone
action (vitamin D/androgen & estrogen) → result hormone dependent cancer
of breast, uterus and prostrate.
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PLP mainly a/w glycogen phosphorylase 4
molecule a/w 1 molecule enzyme
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PLP helps in synthesis of niacin from
tryptophan
Niacin is therefore is not
strictly a vitamin as it can be
synthesised from
tryptophan
Pellagra
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PLP def microcytic hypochromnic anemia
• In heme synthesis condensation reaction
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Transsulfuration reaction
• Pyridoxine used to treat homocysteinuria & cystathionuria
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Oxaluria
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Xanthurenic academia and aciduria
• As Co-enzyme for Kynureninase: an
enzyme for pathway of Niacin
synthesis, from tryptophan Thus in
vit. B6 deficiency, Niacin synthesis
does not taken place.
• In vit-B6 deficiency, Kynurenine and
3-OH kynurenine —v. are converted
into xanthurenic acid in
extrahepatic tissues, which is
excreted in urine. So, “Xanthurenic
acid index” is a reliable criteria for
Vit. B6 deficiency
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• Vit. B6 (Pyridoxine) responsive syndrome (disease) : are
• 1. Infantile convulsions
• 2. Cystathionuria (defect in cystathioninase)
• 3. Homocystinuria (cystathionine synthase)
• 4.Oxaluria
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Pyridoxine def
• Microcytic hypochromic anemia
• Convulsions
• Neuritis
• Involved in sphingomyelin synthesis peripheral neuritis
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Vitamin B6 status can be assessed by
• Activation coefficient
• Activation of RBC Transaminase with PLP
• Xanthurenic acid index
• After tryptophan load test
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Only water soluble vitamin with significant
toxicity
• Neurotoxicity B6 is neurotoxic
• >200mg/day dose
• Partial recovery with residual symptoms
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Biotin / vitamin B7 / vitamin H
• imidazole derivative.
• source →
• Natural food and synthesis from intestinal bacteria (Large portion)
• Consumption of Raw egg can cause Biotin deficiency: - white of egg,
contain a heat — liable protein Avidin which combines very tightly
with biotin, preventing absorption
• C/F — Depression hallucination, muscle pain and dermatitis.
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• Biotin is a co-enzyme of carboxylase enzymes
• A. Pyruvate carboxylase
• B. Acetyl CoA-carboxylase
• C. Propionyl CoA-carboxylase
• D. β-methy1crotony1 CoA carboxylase.
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biotin INDEPENDENT carboxylation
• CPS I & CPS II
• Mallic enzyme
• Fixation of respiratory CO2 during purine synthesis
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Deficiency of biotin
• Spectacle eyed appearance circumocular alopecia
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Pantothenic acid / B5
• Pantoic acid + β alanine linked by peptide bond
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• Building block of coA &
• Citric acid cycle
• FA oxidation
• Acetylation
• Cholesterol synthesis
• Succinyl coA in heme synthesis
• Also building block of acyl carrier protein in FA synthase
• FA synthesis
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Deficiency of pantothenic acid
• Burning foot syndrome
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Vitamin C
• Humans cannot synthesis vitamin c d/t deficiency of gulonolactone
oxidase
• Sources
• Amla
• Orange
• Lemon
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Vitamin c def microcytic hypochromic
anemia
• 2 causes
• Vitamin C is required for absorption of iron
• Haemorrhage
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Vitamin c is also needed in
• In collagen synthesis
• Synthesis of NE ,
• Tryptophan hydroxylase
• Requirement of 7 α hydroxylase in bile acid synthesis
• carnitine , adrenal steroids
• Metabolism of tyrosine &
• folate reductase
• Absorption of fe2+
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• Adrenal glands & lens have a high concentration of vitamin C
• Water soluble anti oxidant
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• Dentine formation is abnormal
• Gums maybe spongy and bleeding
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Subperiosteal hemorrhage
• in distal femur and tibia and proximal humerus,
• causing excruciating tenderness pain near the large joints.
• The child lies still to minimize pain or minimally move the affected
limb (pseudoparalysis) - (Frogs like posture is attained by child)
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Radiological feature d/t poor collagen
formation
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• periosteal reaction due to subperiosteal haemorrhage
• haemarthrosis
• Wimberger's ring sign:
• circular, opaque radiologic shadow surrounding epiphyseal centers of ossification,
which may result from bleeding
• Frankel's line:
• dense zone of provisional calcification
• Trümmerfeld zone:
• lucent metaphyseal band underlying Frankel's line
• Pelken spur: metaphyseal spurs which result in cupping of the metaphysi
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• scorbutic rosary:
• expansion of the
costochondral junctions
• may relate to fracturing of
the zone of provisional
calcification during normal
respiration
• In Rickets—Rosary is Round
and non-tender, and in
Scurvy it is Sharp and tender
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Lab diagnosis of vitamin C
• Blood plasma level < 0.6mg
• Better assessed in buffy coat
• Tyrosine loading test
• Prolonged PT
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• Vitamin B6
• is involved in the transfer of amino groups
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tests for FA
• AICAR excretion
• FIGLU excretion test in FA deficiency
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Vitamin B12
• Extrinsic factor of castle
• B12 is found in food derived from animal sources
• No plant sources
• Synthesised exclusively by micro organisms
• cofactor forms
• Methylcobalamin
• Circuating form
• Bound to transcobalamin
• Homocysteine methyl transferase
• Deoxyadenosylcobalamin
• Storage form
• Bound to transcorrin
• Methyl malonyl coA mutase
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Vitamin with nucleotide in its structure is B12
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• It requires a specific glycoprotein for its absorption.
• lack of intrinsic factordeficiency of vitamin B12
• b. However, high does of the vitamin, given orally, are sufficiently
absorbed to serve as treatment for pernicious anemia.
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• In the stomach gastric enzymes release vitamin B12 from the food and at
gastric pH it binds to R protein.
• The gastric parietal cells produce intrinsic factor which binds to vitamin
B12 at pH of 8.
• In pancreatic insufficiency cbl bound vtaminb12 is excreted
• As gastric emptying occurs, pancreatic secretion raises the pH and vitamin
B12 switches from the R protein to intrinsic factor.
• The vitamin B12 intrinsic factor complex binds to specific receptors in
terminal ileum and vitamin B12 is actively transported by the enterocytes
to plasma.
• Vitamin b12 is absorbed in distal 1/3rd of ileum
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• Only vitamin B12 is stored in body among vitamin b complex
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Blind loop syndrome also can lead to b12
deficiency
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Schilling test to detect b12 absorption
• To detect the cause
• Schilling test (Radioisotope
absorption test)- This test is done to
detect vitamin B12 deficiency as well
as to distinguish and detect lack of
intrinsic factor (IF) and malabsorption.
So schilling test is used for detection
• Good renal function and proper
urinary collection are prerequisite for
schilling test.
• Done in 4 stages
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Stage 1 – Oral vitamin B12 + IM vitamin B12
• 1st small dose of a radioactiove form of B12 by mouth [1 mcg] 2nd
larger dose via intramuscularly [1000 mcg] 1 hour later Collection
of urine after 24 hrs
• * Normal individuals secreates more that 10% of the administered radioactive
vitamin b12 in 24hr urine.
• * Patients with pernicious anemia excretes less that 5% of the administered
dose.
• * If stage 1 is abnormal then stage 2 is done 3-7 days later.
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Stage 2 – Vitamin B12 + Intrinsic factor
• Administer oral radioactive B12 along with intrinsic factor The test
can tells whether low vitamin B12 levels are caused by problems in
the stomach that prevent it from producing intrinsic factor
• If a Stage II test is abnormal, a Stage III test is performed.
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Stage 3 – Vitamin B12 + Antibiotics
• If the defect is still not corrected, then the lesion is in the small
intestine likely The abnormal bacterial flora in the small intestine is
corrected by a 7 day antibiotic course with oral tetracycline
• The test then again repeated after 7 days of the antibiotic therapy.
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Stage 4 – Vitamin B12 + Pancreatic Enzymes
• Intake of pancreatic enzymes for 3 days —–> A small dose of vitamin
B12.
• This test determines whether low vitamin B12 levels are caused by problems
with the pancreas
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Causes of deficiency of B12
• Pernicious anemia
• Gastrectomy
• Gastric atrophy
• True vegetarians
• Perganancy
• Fish tape worm
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Vitamin A
• Vision
• Maintenance of reproduction
• Spermatogenesis
• Maintenance of vaginal & seminal epithelium
• Anti-infective
• Maintenance of epithelial integrity & normal functioning of immunity
• Anti – oxidant
• Anti carcinogenic
• Breast lung oral esophageal cancer prevention
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ROLE OF VITAMIN A IN GENE EXPRESSION
• Homodimers
• Heterodimers
• With vitamin D thyroid hormone
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heterodimer with vitamin A
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• in vitamin A deficiency
decreased 9 cis restinal
active RXR dimers not
formed
• decreased activity of vitamin
D
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Vitamin A deficiency
• Ocular features
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• First sign of vitamin A deficiency
• Decreased sensitivity to green light
• Night blindness
• Bitots spots
• Xerophthalmia
• Keratomalacia
REVERSIBLE
IRREVERSIBLE
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Other features of vitamin A deficiency
• Urogenital epithelium metaplasia infection & scaling
• Dry & scaly skin
• Atrophy of germinal epithelim interfere with reproductive
functions
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Causes of deficiency
• Measles & respiratory tract infection
• Increase demand for vitamin A
• Diarrhea
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• Night blindness is the first symptom and conjunctival xerosis is the
first clinical sign of vitamin A deficiency.
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Prevention
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Vitamin K
• Fat soluble vitamin
• K1 natural
• K2 bacterial
• K3 synthetic
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• Vitamin K activity is found in several compounds of varied origin:
• phylloquinone or vitamin K1 , which is naturally produced by plant sources;
menaquinone or
• vitamin K2, which is produced by microbial sources; and
• menadione or vitamin K3, which is a vitamin precursor of vitamin K2.
• Menadione and its derivatives (synthetic forms of vitamin K) have
been implicated in producing hemolytic anemia and kernicterus in
neonates, especially in premature infants. For this reason, menadione
should not be used as a therapeutic form of vitamin K
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Protein C protein S
osteocalcin
Gamma carboxylation is inhibited
by dicumarol (natural analog of
vitamin K) & warfarin (synthetic
analog of vitamin K)
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Role of vitamin K
• Factor Z,M stimulate platelet activity
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Vitamin E
• Tocopherol
• Α tocopherol is most abundant
• Antisterility
• Antioxidant
• Selenium & vitamin E supplement each others action
• It prevents rancidity of fat by its antioxidant action
• Prevents oxidation of other antioxidants : vitamin A/c
• Protects membrane
• Chainbreaking antioxidant in lipid membranes
• anti
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• The main function of vitamin E (Tocopherol) is as a chain- breaking,
free- radical- trapping antioxidant in cell membranes and plasma
lipoproteins.
It acts by reacting with the lipid peroxide radicals formed by
peroxidation of polyunsaturated fatty acids. The tocopheroxyl radical
product is relatively unreactive, and ultimately forms nonradical
compounds.
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• First line of defence against hydroperoxide free radical damage is
vitamin E (tocopherol) while the second line of defense is a selenium
containing enzyme glutathione peroxidase.
• Vitamin E is destroyed by deep freezing.
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Excess vitamin E bleeding tendency
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Deficiency of vitamin E
• Hemolytic anemia
• d/t its membrane oxidation (vit E is antioxidant )
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• Hypervitaminosis bleeding tendency
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feed back inhibition
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Vitamin D
• Binds to nuclear receptor
• MOST TOXIC VITAMIN
• Increase BP
• Vasoconstriction
• Calcinosis
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• Manganese is an essential trace nutrient in all forms of life.
• The classes of enzymes that have manganese cofactors are very broad
and include
• oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, lectins,
and integrins.
• arginase, the diphtheria toxin, and Mn-containing superoxide dismutase (Mn-
SOD).
• The reverse transcriptases of many retroviruses (though not
lentiviruses such as HIV) contain manganese.
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