Minerals

Copper
Introduction
• Total body copper is about 100 mg.
• It is seen in muscles, liver, bone marrow, brain, kidney, heart and in hair.
• Whole blood contains about 75-150 micrograms/dL of copper..
• Copper containing enzymes are ceruloplasmin,cytochrome oxidase, cytochrome c,
tyrosinase, lysyl oxidase, ALA synthase, monoamine oxidase, superoxide dismutase
and phenol oxidase.
• Copper containing non-enzymatic proteins are hepatocuprein in liver (storage
form), cuprothionine in liver, cerebrocuprein in brain, hemocuprein in RBC and
erythrocuprein in bone marrow.
• Ceruloplasmin is an important antioxidant in plasma.it contains 6-8 cu atoms per
molecule. About 90% of cu content of plasma is bound with ceruloplasmin and 10%
with albumin.
• Cu is bound with albumin loosely and so easily exchanged with tissues. Hence
transport protein for cu is albumin.
RDA & SOURCES
• Copper requirement for an adult is 1.5 – 3 mg per day.
• Major dietary sources are cereals, meat, liver, nuts and green leafy
vegetables.
• Milk is very poor in copper content
Absorption & Excretion

• Cu is absorbed from the intestine.only 10% of dietary cu is absorbed.

• Absorbed cu is bound to albumin is transported to the liver and
incorporated by hepatocytes into cu containing enzymes and proteins.
• Zn interferes with cu absorption.
• Excretion of cu mainly through the bile.urine does not contain cu in
normal circumstances.
Cu Transporters
Cu transporters have a significant role in cu homeostasis.
• Cu tansporter- 1(ctr 1) is an imp cu importer.
• ATP7A &ATP7B is an imp cu exporter.
• The binding of cu by prion proteins may play a role in the brain and
explains the dysfunction of cu homeostasis in Alzeimers disease.
Functions of Copper
• As a component of cytochrome oxidase copper plays main role in
mitochondrial energy production
• In connective tissue Cu is necessary for collagen formation and maturation
• It is necessary for iron absorption and incorporationof iron into hemoglobin.
• It is necessary for tyrosinase activity which helps in melanin synthesis
• It is a co-factor for vitamin C requiring hydroxylations.
• The presence of copper and zinc in superoxide dismutase confers an anti
oxidant role in intra cellular and extra cellular compartments
Abnormal Metabolism of Copper
1. Wilson’s disease: Ceruloplasmin level in blood is drastically reduced in Wilson’s
hepatolenticular degeneration.
• The basic defect is in a gene encoding a copper binding ATPase in cells (ATP7B gene in liver cells).
• This is required for normal excretion of copper from liver cells; in its absence, copper is accumulated in
cells, leading to copper deposits in liver and brain
• Clinical features include cirrhosis, Neurological symptoms and keyser-Fleischer ring in eye
• D-Penicillamine is the chelating agent used in the treatment
• As zinc decreases copper absorption, zinc is sometimes used therapeutically in Wilson’s disease, to
reduce copper load in the body.

2. Aceruloplasminemia: Levels of ceruloplasmin are congenitally low. So, iron is not utilized
properly. Iron accumulates in brain, liver and pancreatic islet cells. Neurological symptoms are seen.
3. Copper deficiency anemia: Copper is essential for formation of
haemoglobin. Copper containing ceruloplasmin helps in iron transport.
• Copper deficiency is manifested as anemia. RBC count is reduced; cell
size is small; but hemoglobin concentration is more or less normal.
Copper deficiency thus results in microcytic normochromic anemia.
4. Cardiovascular diseases: Copper is a constituent of lysyl oxidase. It
oxidizes four lysine residues together to form desmosine which makes
cross linkages in elastin.
• In copper deficiency, elastin becomes abnormal, leading to weakening
of walls of major blood vessels.
• This favors aneurysm and fatal rupture of the wall of aorta.
• Another finding is the fibrosis of myocardium leading to cardiac
failure.
5.Menke’s kinky hair syndrome: It is an x-linked defect (affects only male child).
• It is a condition in which dietary copper is absorbed from GI tract; but cannot be transported to blood
due to absence of an intracellular copper binding ATPase (mutation in ATP7A gene).
• Copper is not mobilized from intestinal cells as well as in other tissue cells.
• The copper that has entered into the cell is not able to get out of the cells, and so it is accumulated.
• Hence, copper is not available for metabolism, resulting in defective cross-linking of connective tissue
• Vascular and connective tissues are affected, and child dies usually in infancy.

6.Melanin: Copper is present in tyrosinase, which is necessary for melanin formation .

• Copper deficiency thus leads to hypopigmentation and in extreme cases, gray color of hair.
• The period of copper deficiency may be marked on hair as alternate white patches; sometimes called flag
type of hair growth.

7. Low levels can cause brain dysfunction especially of the cerebellum, leading to ataxia.
Copper Toxicity
• Excess copper intake may lead to toxic manifestations.
• Copper can oxidize proteins and lipids
• It can enhance production of free radicals.
• Chronic toxicity is manifested as diarrhea and blue-green
discoloration of saliva.
• Copper poisoning may result in hemolysis, hemoglobinuria,
proteinuria and renal failure.
Zinc
Introduction
• Total zinc content of body is about 2 g, out of which 60% is in skeletal
muscles and 30% in bones.
• Highest concentration of zinc is seen in hippocampus area of brain
and prostatic secretion.
Dietary sources
• Rich dietary sources are grains, beans, nuts, cheese, meat and shellfish.
• Copper, calcium, cadmium, iron and phytate will interfere with the
absorption of zinc.
• Zinc and copper will competitively inhibit each other’s absorption.
• So, zinc is therapeutically useful to reduce copper absorption in Wilson’s
disease.
• Daily absorptions is around 10mg
• After absorption zinc is transported to the liver in association with
albumin and the unabsorbed fraction is excreted in feces
Requirement of Zinc
• For adult male is 10-15mg/day
• Adult female – 5-10 mg/day
• In Children 10 mg/day
• In pregnancy and lactation 15–20 mg/day.
• Since iron inhibits absorption of zinc, when iron is supplemented, zinc
is also given to prevent any deficiency.
• On the other hand excess zinc will inhibit absorption of iron and
copper leading to iron /copper deficiencies
Functions of zinc
• More than 300 enzymes are zinc dependent.
• Some important ones are carboxypeptidase, carbonic anhydrase,
alkaline phosphatase, lactate dehydrogenase, ethanol dehydrogenase
and glutamate dehydrogenase.
• RNA polymerase contains zinc and so it is required for protein
biosynthesis.
• Extracellular superoxide dismutase is zinc dependent and so, zinc is an
anti-oxidant.
• Insulin when stored in the beta cells of pancreas contains zinc, which
stabilizes the hormone molecule.
Zinc Deficiency Manifestations
• Poor wound healing, lesions of skin, impaired spermatogenesis,hyperkeratosis,
dermatitis and alopecia are deficiency manifestations of zinc.
• There is reduction in number of T and B lymphocytes. Macrophage function is
retarded.
• Zinc deficiency leads to depression, dementia and other psychiatric disorders.
• Zinc binds with amyloid to form a plaque in Alzheimer’s disease.
• Acrodermatitis Enteropathica is a recessive condition where zinc absorption is
defective and is characterized by acrodermatitis (inflammation around mouth,
nose, fingers, etc.), diarrhea, alopecia (loss of hair in discrete areas),
ophthalmoplegia and hypogonadism
• Chronic deficiency is manifested as leukonychia punctata or “white spots” in
finger nails
Zinc toxicity
• Toxic manifestations are seen when intake is more than 1000 mg/day.
• Toxicity of zinc is usually seen in welders due to inhalation of zinc
oxide fumes.
• Many rat poisons contain zinc compounds, which lead to accidental
poisoning.
• Chronic toxicity may produce gastric ulcer, pancreatitis, anemia,
nausea, vomiting and pulmonary fibrosis.
• Acute toxicity is manifested as fever, excessive salivation, headache
and anemia.
Flouride
Introduction
• Fluoride is known to prevent caries. Caries is a Latin term, meaning “decay”.
• In the pits and fissures of premolar and molar teeth, bacterial fermentation of
residual food leads to acid production.
• The acid removes enamel and dentine to expose the pulp, leading to inflammation
and toothache.
• Topical application of fluoride will result in a fluoroapatite layer on the enamel,
which protects enamel from the decay by acid.
• Fluoride ions enter the hydration shell surrounding the apatite crystals and may
become incorporated into the crystal surface.
• The fluoroapatite makes the tooth surface more resistant to plaque bacterial attack.
• Fluoride rich sources are sea fish, cheese, tea and jowar. Fluorosis is highly prevalent
in areas where jowar is the staple diet.
 Flurosis
• Fluorosis is More Dangerous Than Caries
• The safe limit of fluorine is about 1 ppm in water. (ppm = parts per million; this is equal to 1 mg per 1000
mL).
• Fluoride level more than 2 ppm will cause chronic intestinal upset, gastroenteritis, loss of appetite and
loss of weight.
• Level more than 5 ppm causes mottling of enamel, stratification and discoloration of teeth.
• A level more than 20 ppm is toxic, leading to alternate areas of osteoporosis and osteosclerosis, with
brittle bones. This is called fluorosis.
• Genu valgum is the characteristic feature. Ingested fluoride accumulates in bones.
• In fluorosis, blood concentration of fluoride increases to 50 mcg/100 mL; whereas normal value is 4
mcg/100 mL.
• Due to increased breakdown of bone matrix, excretion of hydroxyproline in urine is enhanced.
• Fluorinated toothpaste contains 3,000 ppm of fluoride. Even ordinary toothpaste contains fluoride about
700 ppm
• Prevention of fluorosis is to provide fluoride free water, restriction of intake of jowar, supplementation of
vitamin C and regulation of fluoride containing toothpaste.
Selenium
Introduction
• Selenium is non metal
• RDA : 50-100 mcg/day. Normal serum level is 50-100 mcg/dl
• Food source: Selenium intake depends on the nature of the soil in
which food crops are grown.
• Most of the selenium in food is available as selenomethionine from
plants
• Dietary selenium is completely absorbed and converted to selenide
and then incorporated in to selenocysteine’
Functions of selenium
• In mammals, glutathione peroxidase (GP) is the important selenium
containing enzyme. RBC contains good quantity of glutathione peroxidase.
• Thyroxin is converted to T3 by 5’-de-iodinase, which is a selenium
containing enzyme. In Se deficiency, this enzyme becomes inactive, leading
to hypothyroidism
• Selenium concentration in testis is the highest in adult tissue. It is necessary
for normal development of spermatozoa. It is concentrated in the mid-
piece of spermatozoa as a specific seleno-protein in mitochondria.
• Selenium acts as a nonspecific intracellular antioxidant. This action of Se is
complementary to vitamin E. Availability of vitamin E reduces the selenium
requirement. In Se deficiency, tissue vitamin E content is depleted.
Selenium deficiency
• Keshan disease : in Keshan province in China, the soil is deficient in
selenium. This leads to prevalence of Keshan disease.
• It is characterized by multifocal myocardial necrosis, cardiac
arrythmias and cardiac enlargement. Selenium is known to cure the
disease.

• Isolated selenium deficiency in other parts of the world caused liver

necrosis, cirrhosis, cardiomyopathy and muscular dystrophy.
Selenium toxicity
• Selenium toxicity is called Selenosis.
• Selenium is present in metal polishes and anti-rust compounds.
• The toxicity symptoms include hair loss, falling of nails, diarrhea,
weight loss, and garlicky odor in breath.
• The last mentioned symptom is due to the presence of dimethyl
selenide in expired air.
Thank you