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2/8/2017 1GANDHAM RAJEEV
• Metabolism of sulfur, iodine, manganese,
fluorine & selenium
– Sources & RDA
– Absorption & excretion
– Biochemical functions
– Disease states
– RGUHS questions
2/8/2017 2GANDHAM RAJEEV
• Sulfur is a component of several biologically
important compounds.
• Proteins contain about 1% sulfur by weight.
• The sulfur containing amino acids
– Methionine, Cysteine or Cystine
• Sulfur containing B-complex vitamins –
– Thiamine (TPP), coenzyme A, lipoic acid & biotin
• Glycosaminoglycans:
– Chondroitin sulfate, heparan sulfate, dermatan
sulfate & keratan sulfate
2/8/2017 3GANDHAM RAJEEV
• Sulfur is present in the food as
– inorganic & organic sulfate (proteins, amino acids
and peptides).
• Major sources - proteins rich in methionine & cysteine.
• Absorption:
• Inorganic sulfate - from the intestine,
• Organic sulfate - active transport
2/8/2017 4GANDHAM RAJEEV
• Formation of active sulfate (PAPS):
• 3-Phosphoadenosine 5-phosphorsulfate(PAPS) is active
sulphate, utilized for several reactions e.g. synthesis of
GAGs & detoxification
• Sulphur-containing amino acids are very essential for
the structural conformation & biological functions of
proteins
2/8/2017 5GANDHAM RAJEEV
• Methionine (as S-adenosylmethionine) is actively
involved in transmethylation reactions & S-
adenosylmethionine also acts as the initiator in
initiation process of protein synthesis.
• Peptides e.g. Glutathione & insulin
• Iron-sulfur proteins are found in ETC
• Sulfur containing vitamins (B1, B5,B7 & lipoic acid) act
as coenzymes.
2/8/2017 6GANDHAM RAJEEV
• Sulfur is oxidized in the liver to sulfate and excreted.
• Urinary sulfur: 1 g/day
• Sulfur is excreted in urine in the form of inorganic
(80%), organic or ethereal sulfate (10%) neutral sulfur
or unoxidized sulfur (10%).
2/8/2017 7GANDHAM RAJEEV
Gandham. Rajeev
2/8/2017 8GANDHAM RAJEEV
• Total body iodine: 20 mg
• 80% is present in the thyroid gland.
• Also present in muscles, salivary glands & ovaries.
• Sources:
• Sea foods, eggs, dairy products, vegetables & iodized
salts.
• RDA:
• Adults: 100 - 150 µg/day
• Pregnant women: 200 µg/day
2/8/2017 9GANDHAM RAJEEV
• From upper small intestine.
• Iodine is transported in plasma by loosely binding
to plasma proteins.
• 80% of body’s iodine is stored in the organic form as
iodothyroglobulin in thyroid gland.
• Iodothyroglobulin contains thyroxine,
diiodotyrosine, & triiodothyronine.
2/8/2017 10GANDHAM RAJEEV
• Iodine is excreted through urine.
• Also excreted through bile, skin & saliva.
• Plasma iodine: 4 – 10 mg/dl.
• Most of this is present as protein bound iodine (PBI).
• It represents the iodine levels.
• PBI:
– Increased in hyperthyroidism
– Decreased in hypothyroidism
2/8/2017 11GANDHAM RAJEEV
• Most important functions
– Synthesis of thyroid hormones, triiodothyronine
(T3) and tetraiodothyronine (T4) in thyroid gland.
– 125 I is used as radioactive label in the
radioimmunoassay of hormones (T3 & T4)
– 131 I is used for the assessment of thyroid
malignancy & treatment of thyrotoxicosis.
2/8/2017 12GANDHAM RAJEEV
• Iodine deficiency: Goiter
• Causes:
– Dietary deficiency
– Ingestion of goitrogens in the diet.
• Dietary deficiency:
• Low content of iodine in soil & water.
• Jammu & Kashmir, Karnataka, Punjab, Himachal
Pradesh, Maharashtra & kerala show higher
incidence of goiter.
2/8/2017 13GANDHAM RAJEEV
• Abnormal increase in size of the thyroid gland is
known as goiter.
– Decreased synthesis of thyroid hormones & is
associated with elevated TSH.
– Goiter is primarily due to a failure in the auto
regulation of T3 & T4 synthesis.
– Caused by deficiency or excess of iodide
2/8/2017 14GANDHAM RAJEEV
• Substances that interfere with the utilization of iodine
for the synthesis of thyroid hormones
• Thiocyanates – present in cabbage, cauliflower &
they inhibit uptake of iodine by thyroid glans.
• Drugs - thiourea, thiouracil, thiocarbamide – inhibits
iodination process.
2/8/2017 15GANDHAM RAJEEV
• Iodine deficiency is known as simple goiter.
• Characterized by swelling of thyroid gland &
features of hypothyroidism (slow pulse, myxedema)
• Iodine deficiency in pregnant women results in
impaired fetal growth & brain development.
• Treatment:
• Consumption of iodized salt is advocated
• Administration of thyroid hormone is also employed.
2/8/2017 16GANDHAM RAJEEV
2/8/2017 17GANDHAM RAJEEV
2/8/2017 18GANDHAM RAJEEV
• Total body content of manganese is 15 mg
• Present in the liver & kidney.
• It is associated with connective & bony tissue,
growth & reproductive functions, carbohydrate &
lipid metabolism.
• Sources:
– Liver, kidneys, whole grain cereals, vegetables &
nuts.
– Tea is a rich source of manganese.
2/8/2017 19GANDHAM RAJEEV
• RDA:
• 2.5 to 5 mg/day.
• Serum manganese: 5-20 mg/dl.
• Absorption:
• From the small intestine.
• Calcium, phosphorous & iron inhibit manganese
absorption.
2/8/2017 20GANDHAM RAJEEV
• Role in enzyme action:
• Acts as a ‘cofactor’ or activator of many enzymes like
– Arginase,
– Isocitrate dehydrogenase (ICD),
– Cholinesterase,
– Lipoprotein lipase,
– Enolase,
– Pyruvate carboxylase
– SOD (Mitochondria)
2/8/2017 21GANDHAM RAJEEV
• Manganese is essential for
– Formation of bone, proper reproduction, functioning
of nervous system
– Hemoglobin synthesis
– Inhibition of lipid peroxidation
– Cholesterol & fatty acid biosynthesis
– Function with vitamin K in the formation of
prothrombin.
• Manganese & magnesium may replace one another in
case of some of the enzymes.
2/8/2017 22GANDHAM RAJEEV
• Manganese deficiency is not seen in humans,
adequate supply in normal diet
• Manganese deficiency in animals causes
– Retarded growth, bone deformities, sterility.
– Fatty liver, increased ALP, diminished activity of β –
cells of pancreas.
• Toxicity:
• Caused by industrial exposure to manganese.
• Symptoms:
• Psychiatric
2/8/2017 23GANDHAM RAJEEV
Gandham. Rajeev
2/8/2017 24GANDHAM RAJEEV
• It is mainly found in bones & teeth.
• Sources:
– Drinking water.
• The content of fluorine in water is dependent on the
soil content of fluorine.
• RDA:
• 1-2 ppm (parts per million).
• Fluorine is supplemented in various tooth paste
preparations.
2/8/2017 25GANDHAM RAJEEV
• Inorganic fluoride is absorbed readily in the
stomach & small intestine and distributed almost
entirely to bone and teeth.
• About 50% of the daily intake is excreted through
urine.
2/8/2017 26GANDHAM RAJEEV
• Required for the proper formation of bones & teeth.
• Fluoride, prevents the development of dental caries,
• It forms a protective layer of acid resistant
fluoroapatite with hydroxyapatite of enamel, which
increases hardness of bone & teeth & provides
protection against dental caries & attack by acids.
• Sodium fluoride inhibits enolase & fluoroacetate
inhibits aconitase
2/8/2017 27GANDHAM RAJEEV
• Causes:
• Drinking water that is low in fluorine content.
• Fluorine deficiency causes dental caries.
• Toxicity:
• Causes:
• Drinking water contains >5 ppm of fluorine.
• Features:
• Result in dental fluorosis & skeletal fluorosis.
2/8/2017 28GANDHAM RAJEEV
• Dental fluorosis:
• It is an important public health problem in several
countries including India.
• Features:
• It is characterized by mottling of enamel &
discoloration of teeth.
• Skeletal fluorosis:
• If the ingestion of fluorine is very high (more than 10
ppm), the condition leads to skeletal fluorosis
2/8/2017 29GANDHAM RAJEEV
• Features:
• Hypercalcification, increasing the density of bones of
limbs, pelvis & spine.
– Bone deformities such as bowed legs, bending of
spine & osteoporosis.
– Ligaments of spine & collagen of bones also
calcified.
• In advanced stages,
– Individuals cannot perform their routine work due
to stiff joints.
– Advances fluorosis is referred to as genu valgum
2/8/2017 30GANDHAM RAJEEV
Gandham. Rajeev
2/8/2017 31GANDHAM RAJEEV
• Total body content of selenium 10 mg
• Mainly present in liver.
• Selenium was found to prevent liver cell necrosis &
muscular dystrophy.
• Sources:
– Meat, sea foods, liver, kidney
• RDA
• 50 to 100 µg/day.
2/8/2017 32GANDHAM RAJEEV
• From the duodenum.
• After absorption, transported by plasma proteins
particularly β-lipoproteins
• Excreted through urine.
2/8/2017 33GANDHAM RAJEEV
• Selenium
– Along with vitamin E, prevents development of
hepatic necrosis & muscular dystrophy
– Involved in maintaining structural integrity of cell
membranes.
– Selenocysteine is an essential component of
glutathione peroxidase (antioxidant enzyme)
– Prevents lipid peroxidation & protects the cells
against free radicals.
2/8/2017 34GANDHAM RAJEEV
• Binds with certain heavy metals (Hg, Cd) & protects
the body from their toxic effects.
• 5'-deiodinase- selenium containing enzyme converts
thyroxine (T4) to triiodithyronine (T3) in thyroid gland.
• In selenium deficiency, conversion of T4 to T3 is
impaired resulting in hypothyroidism.
• Thioredoxin reductase – contains selenium, involved
in purine metabolism.
2/8/2017 GANDHAM RAJEEV 35
• Selenium in the diet reduces the requirement of
vitamin E.
• Selenium may exert anticancer effects because of its
antioxidant role.
• Selenocysteine is considered as 21st amino acid, it is
coded by UGA, which is a termination codon.
• Selenium is incorporated to proteins as
selenocysteine during protein synthesis.
2/8/2017 GANDHAM RAJEEV 36
• Causes:
– Low soil content of selenium & malnutrition.
• Clinical features:
• Keshan disease, an endemic cardiomyopathy in China
– Associated with cirrhosis of liver
– Cardiomyopathy leading to congestive cardiac
failure,
– Multifocal myocardial necrosis
– Cardiac arrythmias
2/8/2017 37GANDHAM RAJEEV
2/8/2017 38GANDHAM RAJEEV
• Muscular dystrophy
• Loss of appetite
• Nausea
2/8/2017 39GANDHAM RAJEEV
• Selenium toxicity is called as Selenosis & it is rare.
• Seen in people who handle metal polishes & anti-rust
compounds.
• Clinical features
– Hair loss
– Dermatitis & irritability
– Diarrhea & weight loss
2/8/2017 40GANDHAM RAJEEV
• It is a constituent of the enzymes xanthine oxidase,
aldehyde oxidase, sulfite oxidase.
• Sources: milk, beans, cereals.
• RDA: 200 μg/day
• Absorbed by small intestine
• Deficiency: Very rare in humans
• Toxicity: Seen in areas where the molybdenum
content of soil is very high
• Feature: Growth failure, anemia, diarrhea & gout.
2/8/2017 GANDHAM RAJEEV 41
1. PAPS
2. Functions of manganese
3. Functions of iodine
4. Fluorosis
5. Biochemical functions of selenium
2/8/2017 GANDHAM RAJEEV 42
• Text book of Biochemistry - U Satyanarayana
• Text book of Biochemistry – DM Vasudevan
• Text book of Biochemistry - MN Chatterjea
2/8/2017 43GANDHAM RAJEEV
Thank You
2/8/2017 44GANDHAM RAJEEV

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METABOLISM OF SULFUR, IODINE, MANGANESE,FLUORINE & SELENIUM

  • 2. • Metabolism of sulfur, iodine, manganese, fluorine & selenium – Sources & RDA – Absorption & excretion – Biochemical functions – Disease states – RGUHS questions 2/8/2017 2GANDHAM RAJEEV
  • 3. • Sulfur is a component of several biologically important compounds. • Proteins contain about 1% sulfur by weight. • The sulfur containing amino acids – Methionine, Cysteine or Cystine • Sulfur containing B-complex vitamins – – Thiamine (TPP), coenzyme A, lipoic acid & biotin • Glycosaminoglycans: – Chondroitin sulfate, heparan sulfate, dermatan sulfate & keratan sulfate 2/8/2017 3GANDHAM RAJEEV
  • 4. • Sulfur is present in the food as – inorganic & organic sulfate (proteins, amino acids and peptides). • Major sources - proteins rich in methionine & cysteine. • Absorption: • Inorganic sulfate - from the intestine, • Organic sulfate - active transport 2/8/2017 4GANDHAM RAJEEV
  • 5. • Formation of active sulfate (PAPS): • 3-Phosphoadenosine 5-phosphorsulfate(PAPS) is active sulphate, utilized for several reactions e.g. synthesis of GAGs & detoxification • Sulphur-containing amino acids are very essential for the structural conformation & biological functions of proteins 2/8/2017 5GANDHAM RAJEEV
  • 6. • Methionine (as S-adenosylmethionine) is actively involved in transmethylation reactions & S- adenosylmethionine also acts as the initiator in initiation process of protein synthesis. • Peptides e.g. Glutathione & insulin • Iron-sulfur proteins are found in ETC • Sulfur containing vitamins (B1, B5,B7 & lipoic acid) act as coenzymes. 2/8/2017 6GANDHAM RAJEEV
  • 7. • Sulfur is oxidized in the liver to sulfate and excreted. • Urinary sulfur: 1 g/day • Sulfur is excreted in urine in the form of inorganic (80%), organic or ethereal sulfate (10%) neutral sulfur or unoxidized sulfur (10%). 2/8/2017 7GANDHAM RAJEEV
  • 9. • Total body iodine: 20 mg • 80% is present in the thyroid gland. • Also present in muscles, salivary glands & ovaries. • Sources: • Sea foods, eggs, dairy products, vegetables & iodized salts. • RDA: • Adults: 100 - 150 µg/day • Pregnant women: 200 µg/day 2/8/2017 9GANDHAM RAJEEV
  • 10. • From upper small intestine. • Iodine is transported in plasma by loosely binding to plasma proteins. • 80% of body’s iodine is stored in the organic form as iodothyroglobulin in thyroid gland. • Iodothyroglobulin contains thyroxine, diiodotyrosine, & triiodothyronine. 2/8/2017 10GANDHAM RAJEEV
  • 11. • Iodine is excreted through urine. • Also excreted through bile, skin & saliva. • Plasma iodine: 4 – 10 mg/dl. • Most of this is present as protein bound iodine (PBI). • It represents the iodine levels. • PBI: – Increased in hyperthyroidism – Decreased in hypothyroidism 2/8/2017 11GANDHAM RAJEEV
  • 12. • Most important functions – Synthesis of thyroid hormones, triiodothyronine (T3) and tetraiodothyronine (T4) in thyroid gland. – 125 I is used as radioactive label in the radioimmunoassay of hormones (T3 & T4) – 131 I is used for the assessment of thyroid malignancy & treatment of thyrotoxicosis. 2/8/2017 12GANDHAM RAJEEV
  • 13. • Iodine deficiency: Goiter • Causes: – Dietary deficiency – Ingestion of goitrogens in the diet. • Dietary deficiency: • Low content of iodine in soil & water. • Jammu & Kashmir, Karnataka, Punjab, Himachal Pradesh, Maharashtra & kerala show higher incidence of goiter. 2/8/2017 13GANDHAM RAJEEV
  • 14. • Abnormal increase in size of the thyroid gland is known as goiter. – Decreased synthesis of thyroid hormones & is associated with elevated TSH. – Goiter is primarily due to a failure in the auto regulation of T3 & T4 synthesis. – Caused by deficiency or excess of iodide 2/8/2017 14GANDHAM RAJEEV
  • 15. • Substances that interfere with the utilization of iodine for the synthesis of thyroid hormones • Thiocyanates – present in cabbage, cauliflower & they inhibit uptake of iodine by thyroid glans. • Drugs - thiourea, thiouracil, thiocarbamide – inhibits iodination process. 2/8/2017 15GANDHAM RAJEEV
  • 16. • Iodine deficiency is known as simple goiter. • Characterized by swelling of thyroid gland & features of hypothyroidism (slow pulse, myxedema) • Iodine deficiency in pregnant women results in impaired fetal growth & brain development. • Treatment: • Consumption of iodized salt is advocated • Administration of thyroid hormone is also employed. 2/8/2017 16GANDHAM RAJEEV
  • 19. • Total body content of manganese is 15 mg • Present in the liver & kidney. • It is associated with connective & bony tissue, growth & reproductive functions, carbohydrate & lipid metabolism. • Sources: – Liver, kidneys, whole grain cereals, vegetables & nuts. – Tea is a rich source of manganese. 2/8/2017 19GANDHAM RAJEEV
  • 20. • RDA: • 2.5 to 5 mg/day. • Serum manganese: 5-20 mg/dl. • Absorption: • From the small intestine. • Calcium, phosphorous & iron inhibit manganese absorption. 2/8/2017 20GANDHAM RAJEEV
  • 21. • Role in enzyme action: • Acts as a ‘cofactor’ or activator of many enzymes like – Arginase, – Isocitrate dehydrogenase (ICD), – Cholinesterase, – Lipoprotein lipase, – Enolase, – Pyruvate carboxylase – SOD (Mitochondria) 2/8/2017 21GANDHAM RAJEEV
  • 22. • Manganese is essential for – Formation of bone, proper reproduction, functioning of nervous system – Hemoglobin synthesis – Inhibition of lipid peroxidation – Cholesterol & fatty acid biosynthesis – Function with vitamin K in the formation of prothrombin. • Manganese & magnesium may replace one another in case of some of the enzymes. 2/8/2017 22GANDHAM RAJEEV
  • 23. • Manganese deficiency is not seen in humans, adequate supply in normal diet • Manganese deficiency in animals causes – Retarded growth, bone deformities, sterility. – Fatty liver, increased ALP, diminished activity of β – cells of pancreas. • Toxicity: • Caused by industrial exposure to manganese. • Symptoms: • Psychiatric 2/8/2017 23GANDHAM RAJEEV
  • 25. • It is mainly found in bones & teeth. • Sources: – Drinking water. • The content of fluorine in water is dependent on the soil content of fluorine. • RDA: • 1-2 ppm (parts per million). • Fluorine is supplemented in various tooth paste preparations. 2/8/2017 25GANDHAM RAJEEV
  • 26. • Inorganic fluoride is absorbed readily in the stomach & small intestine and distributed almost entirely to bone and teeth. • About 50% of the daily intake is excreted through urine. 2/8/2017 26GANDHAM RAJEEV
  • 27. • Required for the proper formation of bones & teeth. • Fluoride, prevents the development of dental caries, • It forms a protective layer of acid resistant fluoroapatite with hydroxyapatite of enamel, which increases hardness of bone & teeth & provides protection against dental caries & attack by acids. • Sodium fluoride inhibits enolase & fluoroacetate inhibits aconitase 2/8/2017 27GANDHAM RAJEEV
  • 28. • Causes: • Drinking water that is low in fluorine content. • Fluorine deficiency causes dental caries. • Toxicity: • Causes: • Drinking water contains >5 ppm of fluorine. • Features: • Result in dental fluorosis & skeletal fluorosis. 2/8/2017 28GANDHAM RAJEEV
  • 29. • Dental fluorosis: • It is an important public health problem in several countries including India. • Features: • It is characterized by mottling of enamel & discoloration of teeth. • Skeletal fluorosis: • If the ingestion of fluorine is very high (more than 10 ppm), the condition leads to skeletal fluorosis 2/8/2017 29GANDHAM RAJEEV
  • 30. • Features: • Hypercalcification, increasing the density of bones of limbs, pelvis & spine. – Bone deformities such as bowed legs, bending of spine & osteoporosis. – Ligaments of spine & collagen of bones also calcified. • In advanced stages, – Individuals cannot perform their routine work due to stiff joints. – Advances fluorosis is referred to as genu valgum 2/8/2017 30GANDHAM RAJEEV
  • 32. • Total body content of selenium 10 mg • Mainly present in liver. • Selenium was found to prevent liver cell necrosis & muscular dystrophy. • Sources: – Meat, sea foods, liver, kidney • RDA • 50 to 100 µg/day. 2/8/2017 32GANDHAM RAJEEV
  • 33. • From the duodenum. • After absorption, transported by plasma proteins particularly β-lipoproteins • Excreted through urine. 2/8/2017 33GANDHAM RAJEEV
  • 34. • Selenium – Along with vitamin E, prevents development of hepatic necrosis & muscular dystrophy – Involved in maintaining structural integrity of cell membranes. – Selenocysteine is an essential component of glutathione peroxidase (antioxidant enzyme) – Prevents lipid peroxidation & protects the cells against free radicals. 2/8/2017 34GANDHAM RAJEEV
  • 35. • Binds with certain heavy metals (Hg, Cd) & protects the body from their toxic effects. • 5'-deiodinase- selenium containing enzyme converts thyroxine (T4) to triiodithyronine (T3) in thyroid gland. • In selenium deficiency, conversion of T4 to T3 is impaired resulting in hypothyroidism. • Thioredoxin reductase – contains selenium, involved in purine metabolism. 2/8/2017 GANDHAM RAJEEV 35
  • 36. • Selenium in the diet reduces the requirement of vitamin E. • Selenium may exert anticancer effects because of its antioxidant role. • Selenocysteine is considered as 21st amino acid, it is coded by UGA, which is a termination codon. • Selenium is incorporated to proteins as selenocysteine during protein synthesis. 2/8/2017 GANDHAM RAJEEV 36
  • 37. • Causes: – Low soil content of selenium & malnutrition. • Clinical features: • Keshan disease, an endemic cardiomyopathy in China – Associated with cirrhosis of liver – Cardiomyopathy leading to congestive cardiac failure, – Multifocal myocardial necrosis – Cardiac arrythmias 2/8/2017 37GANDHAM RAJEEV
  • 39. • Muscular dystrophy • Loss of appetite • Nausea 2/8/2017 39GANDHAM RAJEEV
  • 40. • Selenium toxicity is called as Selenosis & it is rare. • Seen in people who handle metal polishes & anti-rust compounds. • Clinical features – Hair loss – Dermatitis & irritability – Diarrhea & weight loss 2/8/2017 40GANDHAM RAJEEV
  • 41. • It is a constituent of the enzymes xanthine oxidase, aldehyde oxidase, sulfite oxidase. • Sources: milk, beans, cereals. • RDA: 200 μg/day • Absorbed by small intestine • Deficiency: Very rare in humans • Toxicity: Seen in areas where the molybdenum content of soil is very high • Feature: Growth failure, anemia, diarrhea & gout. 2/8/2017 GANDHAM RAJEEV 41
  • 42. 1. PAPS 2. Functions of manganese 3. Functions of iodine 4. Fluorosis 5. Biochemical functions of selenium 2/8/2017 GANDHAM RAJEEV 42
  • 43. • Text book of Biochemistry - U Satyanarayana • Text book of Biochemistry – DM Vasudevan • Text book of Biochemistry - MN Chatterjea 2/8/2017 43GANDHAM RAJEEV