Biochemistry lecture on copper

1. BIOCHEM 612
COPPER AS VITAL MICRONUTRIENT

2. INTRODUCTION
• Copper is an essential trace element which is a
component of many intracellular
metalloenzymes.
• Copper is present in all metabolically active
tissues.
• The highest concentrations are found in liver
and kidney, with significant amount in cardiac
& skeletal muscles and bones.
• The liver contains 10% of the total body
content of 80mg.

3. • Sources of copper Average diet provides 2 to 4
mg/day of copper in the form of : • Meat, •
Shellfish, • Legumes, • Nuts and cereals • Milk
and milk-products are poor sources.
• 6. Daily Requirements • Infants and children:
0.05 mg Cu/kg body wt. per day • Adult
requirement: approximately 2.5 mg/day. •
Normal diets contain about 2.5 to 5.0 mg Cu.

4. Distribution
• Requirements
• Infants and children: 0.05 mg Cu/kg body wt. per day
• Adult requirement: Is approximately 2.5 mg/day.
Ordinary diets consumed daily contain about 2.5 to 5.0 mg Cu.
Whole body 100 to 150 mg
Muscles, 65 mg /100gm
Bones 23 mg /100gm
Liver 18 mg /gm
Brain 0.02 mg /gm

5. It occurs as:
1. Erythrocuprein (in red blood cells),
2. Hepatocuprein (in liver) and
3. Cerebrocuprein (in brain)

6. METABOLISM
• APSORPTION
• TRANSPORTATION
• CELLULAR UPTAKE
• REGULATION

7. ABSORPTION
• Primarily absorbed from the
duodenum.
• Dietary cu++ is first reduced to cu+
by reductase enzyme.
• About 32% of the dietary Cu can be
absorbed via a transporter CTR1
(Copper transport protein 1).
• Once copper enters cytoplasm it is
attached to Antioxidant protein
ATOX1 (copper metal
chaperone protein) and
metalothionien.
• ATOX1 and metalothionien deliver
copper to trans-golgi network via
ATP7A transporter from where it is
release to portal circulation .
Portal Circulation

8. TRANSPORTAION
• In portal blood circulation copper is transported to liver
in loosely bound form with albumin protein.
Copper is transported in blood in two forms
• Free Serum copper: loosely bounded to plasma
albumin protein.
• Bound form: Which remains bound to α-globulin called
“Caeruloplasmin” .
• About 96 per cent of serum Cu is found in combined
form with caeruloplasmin.
Total serum copper (bound + free)

9. Hepatic Uptake
• Albumin bounded copper is taken up by
hepatocytes by a transporter protein
CTR1.
• Copper ion are transported to Golgi
apparatus by ATP7B transporter
protein.
• The copper is then bind to apo-
caeruloplasmin to produced holo-
ceaeruplasmin, which is transported to
blood by the help of ATP7B transporter
protein.
• 96 per cent of serum Cu is found in
combined form with caeruloplasmin
and is transported to different tissues
for its further use for the production of
biologically important enzymes i.e.
 Cytochrom C……….ATP in ETC
 Lysyl oxidase-------Collagen
 SOD------------MANANGEMENT OF ROS
 Tyrosinase----------Melanin
Excess caeruloplasmin is excreted in bile.

10. REGULATION
• High intracellular copper, activates
hydroxylase enzyme which delocalizes ATP7A
to the plasma membrane to facilitate copper
export.
• High blood caeruloplasmin triggers activation
of COMMD1 (Copper Metabolism Domain
Containing 1) protein.
• COMMD1 is activated for the downregulation
of CTR1 gene.

11. FUNCTIONS
• Cu forms integral part of certain enzymes, e.g.
some of cytochromes, cytochrome oxidase,
tyrosinase.
• Cu helps in the utilization of Fe for Hb synthesis in
the body.
• Copper has been reported to help in the
formation of bones and maintenance of myelin
sheaths of nerve-fibres.

12. CLINICAL ASPECT
MENKE’S DISEASE :Kinky or Steel hair syndrome
• It is copper deficiency disease which is X
linked.
• It is caused by the mutation in the ATP7A
gene “(copper binding P typeATPase)”.
• This ATPase is thought to be responsible for
directing the efflux of copper from cells.
• When altered by mutation, copper is not
mobilized normally from the intestine in
which it accumulates.
• Symptoms
 Osteogenesis imperfecta
 Pale complexation
 Decrease mental activities
 Kinky hairs

13. WILSON’S DISEASE (hepatolenticular
degeneration):
• It is inherited as autosomal recessive
disease.
• Caused by mutation in ATPaseB
results in accumulation of copper in
liver brain and other vital organs.
• Symptoms
 Parkinson’s disease like symptoms
due to Brain damage
 Dimentia due to cortex damage
 Kayser-Fleischer ring”. golden
brown, yellow or green ring round
the cornea
 Liver cirrhosis

14. CLASS ACTIVITIES
1. When intestinal or liver cells are overloaded with copper then
what could be the consequences?
2. What is ATOX1 . Explain its importance.
3. Function of ATPase A and ATPase B protein.
4. How will you explain MENKE’S DISEASE symptoms.
5. A 15 –year-old girl presented with abdominal pain and diarrhea
for 3 days. • She became jaundiced and a presumptive diagnosis
of infective hepatitis was made, but serological tests were
negative. • She subsequently died of liver failure. • At post-
mortem, her liver copper concentration was found to be grossly
increased. • What is the probable diagnosis?
Case details • High liver copper concentration, indicates that the
patient died of Wilson’ disease, • It is an autosomal recessive disorder.
• Clinical manifestations are caused by copper toxicity.