Trace Elements (Iodine, Copper, Selenium and Aluminium)) Flashcards
How much iodine is required daily?
about 150 micrograms
What is the function of iodine in the body
substrate used for thyroid hormone synthesis
Where is iodine primarily found and what foods are a good source of iodine?
primarily found in ocean (seafood and kelps)
food sources:
- fairy products
- seafood
- seaweed
- eggs
- bread
- some vegetables
Due to iodines low environmental levels it is the number one cause of
preventable intellectual disability in children
What are the 2 thyroid hormones?
- thyroxine (T4) prohormone
- transport from cell to cell form
- longer half life and more stable - triiodothyronine (T3)
- active form
Where is the thyroid gland located
on trachea
- 2 lobes joined by narrow isthmus
filled with major thyroid secretory cells around in hollow spheres (follicles)
What is the structure of the follicles in the thyroid gland
secretory cells (follicular cells) form rings around inner lumen (colloid) with a C cell in the connective tissue associated with the follicle
- colloid serves as the extracellular storage and production site of thyroid hormones
- C cells secrete calcitonin which regulates blood calcium levels and stops the breakdown of bone by releasing osteoclasts by releasing Ca2+
Where are thyroid hormones mostly found other than the thyroid gland
circulating in plasma:
- most complexed to T4 binding globulin
- small amount free active T3
How are thyroid hormone regulated
- thyrotropin-releasing hormone (TRH) secreted by the hypothalamus
- TRH stimulates thyroid stimulating hormone (TSH) produced by the anterior pituitary gland
- TSH regulates T3 and T4 synthesis in the thyroid gland
What is the first step in thyroid hormone synthesis
thyroglobulin (Tg) is synthesised in the rough ER and enters the colloid by exocytosis
meanwhile a sodium/iodide symporter (Na/I) pumps iodide actively into the cell
What is the second step in thyroid hormone synthesis
Iodide enters the colloid from cytoplasm by pendrin transporter and TPO (thyroperoxidase) converts iodide into active iodine
iodine iodinates Tg at tyrosyl residues causing the adjacent iodinated tyrosyl residues to be paired together forming MIT (monoiodotyrosine) and DIT (diiodotyrosine)
What is the third step in thyroid hormone synthesis
Tg then re-enters the follicular cell by endocytosis where lysosomes fuse and proteolysis occurs which liberates T3 and T4 molecules
T3 and T4 in cytoplasm then enter the colloid
What is the function of TSH other than stimulating the production of thyroid hormones
- stimulates expression of transporters and enzymes involved in T3 and T4 production (and endocytosis of Tg)
- also stimulates growth of thyroid gland
What happens when is no or excess TSH
no TSH = thyroid atrophies (shrinks)
- hypothyroidism
- hormones released at very low rate
too much TSH = thyroid hypertrophies
- hyperthyroidism
What is the consequence of iodine deficiency during pregnancy
stillbirth
spontaneous abortion
congenital abnormalities
if child is born can result in:
- stunted growth
- diminished intelligence
- retardation
Where is iodine deficiency most prominent
developing countries
- himalayas
- andes
- africa
How was iodine deficiency improved in australia?
iodised salt
iodised water
bread made with iodised salt
- provides enough iodine to avoid low thyroid activity for most people
What are the effects of long term iodine deficiency
thyroid gland adapt to insufficient supply of iodine by increasing trapping
- Goitre occurs (increase size of thyroid gland)
- hypothyroidism occurs (not enough thyroid hormones produced)
What are the symptoms of long term iodine deficiency
dry skin
hair loss
decreased metabolic rate
- fatigue/ lethargy
slowed reflexes
constipation
How is the negative feedback loop for thyroid hormone stimulation affected in hypothyroidism
due to lack of T3 and T4 being released from thyroid the hypothalamus keeps secreting TRH and in turn TSH.
As TSH keeps being secreted a goiter occurs
Are goiters found in iodine deficient children
no just adults
What is the symptoms of iodine toxicity
burning of mouth, throat and stomach
fever
nausea
vomiting
diarrhea
weak pulse
cyanosis
coma
What can cause iodine toxicity
- iodine supplementation programmes in iodine deficient populations
- can result in iodine induced hyperthyroidism (especially if goiter present) - excess iodine intake in healthy individuals
- elevated blood concentrations of TSH but inhibits thyroid hormone production
- leads to hypothyroidism and goiter (but not known how)
Iodine toxicity leads to Wolff Chaikoff effect. What is this effect?
reduction of thyroid hormone levels caused by ingestion of large amounts of iodine by rejecting the large amounts of iodine
How much copper is required per day? does this differ from the amount a regular diet provide?
required: about 900 micrograms
regular diet: 1-1.5 micrograms per day
What are good food sources for copper?
oysters and shellfish
seeds and nuts
meats (high in kidney and liver)
whole grains
What key enzymes in the body is copper essential in?
- superoxide dismutase
- removes superoxides by converting them into hydrogen peroxide - lysyl oxidase (extracellular copper enzyme)
- needed for collagen and elastin synthesis - cytochrome c oxidase
- last enzyme in the electron transport chain
Where in the process of collagen synthesis and secretion is lysyl oxidase needed?
After tropocollagen is formed Cu dependant lysyl oxidase deaminates lysine and hydroxylysine residues to form aldehyde groups which forms cross links
- turns tropocollagen into final collagen product
Where in the electron transport chain does cytochrome c oxidase (complex IV) used and what is its function?
- sugars and fatty acids are oxidised to acetyl CoA
- acetyl CoA oxidised to generate NADH
- electrons from NADH are passed down the electron transport chain which creates energy to generate a proton gradient across the mito inner membrane
- cytochrome c oxidase is the last enzyme in this chain which oxidises 3 cytochrome c molecules (reducing O2 to 2H20)
What does copper deficiency cause
- decreased cross linking of collagen and elastin (lack of
lysyl oxidase) - poor bone formation and strength
- hyperextensible skin and weak ligaments
- increased occurrence of aortic aneurysms
- increase ROS (lack of SOD)
- loss of complex IV activity/ATP generation (lack of cytochrome c oxidase)
What is the most common cause of copper deficiency
malabsorption of copper or zinc toxicity
(zinc competitively binds to MET in gut enterocytes)
What is a copper deficiency genetic disease and what is the genetic basis of the disease
Menkes disease
- X linked recessive disorder (congenital)
When does Menkes disease onset occurs and what does it result in?
onset: during infancy
result: growth failure and nervous system deterioration
What is the molecular basis of Menkes disease
causes a defect in ATP7A (transporter expressed on most tissues except the liver)
- defect in copper transporting protein in trans-golgi network which impaires copper absorption in gut
- low copper in many tissues which accumulates in kidneys
What are the symptoms of copper toxicity
yellowing of eye (Kayser Fleischer rings)
metallic taste
anaemia
vomiting, nausea, abdominal pain
no urine production
diarrhea
yellowing of skin
muscle weakness
chills, fever and systemic pain
What is excess copper in the body known as and what does it occur from?
copperiedus
occurs from:
- ingesting acidic foods cooked in uncoated copper cookware
- exposure to excess copper in drinking water or other environmental sources
Wilson’s disease is a genetic disease causing copper toxicity. What is the molecular basis of this disease?
defect in transporter ATP7B
- expressed in brain, liver and kidney
- involved in copper export out of cell
A defect in this transporter leads to copper levels building up in the liver which then overflow and cause a build up in brain and kidneys
What is a major consequence of copper toxicity in Wilson’s disease
high amounts of copper leads to the Fenton reaction occuring more than normal leading to increased ROS production
How is Wilson’s disease treated
treated with chelators and or zinc
What is the main symptom of Wilsons disease
Keyser-Fleischer rings around iris
What is the difference between Menkes and Wilsons
Menkes
- affects ATP7A transporter so copper cannot get into the cell
Wilsons
- affects ATP7B transporter so copper cannot get out of the cell
What kind of element is Selenium and what is its function in the body
non metal found in minerals
function: incorporated into proteins to form selenoproteins which contain selenocysteine residues
What are some examples of selenoproteins
- selenoprotein P
- found in blood plasma
- may be an antioxidant - glutathione peroxidase (GPx)
- Iodothyronine deiodinases
What is the role of glutathione peroxidase
reacts with glutathione and hydrogen peroxidase which reduces hydrogen peroxidase to water and produces oxidised glutathione (GSSG)
What is the role of Iodothyronine deiodinases in thyroid hormone synthesis?
iodine removed from MIT and DIT through this selenoproteins
- this allows iodine to be recycled
What are good food sources for selenium?
nuts (brazil nuts especially)
cereals
meat
mushrooms
fish
eggs
What is the optimal dietary daily intake of selenium?
40 micrograms per day
What disease does Selenium deficiency cause?
Keshan disease
What does Keshan disease cause
cardiomyopathy (white muscle disease)
- due to defects in GPx leads to bleaching by peroxides and hydroperoxides
Can Keshan disease be reversed by selenium supplements
no
How much selenium per day can cause selenosis (selenium toxicity)
400 micrograms per day
What is the most common way to be exposed to toxic amounts of selenium
exposure to smoke of burning coal containing Se
What are the symptoms of Se poisoning
garlic odour breath
gastrointestinal disorders
hair loss and sloughing of nails
fatigue and irritability
neurological damage
cirrhosis of the liver
pulmonary edema
There were 3 major outbreaks of Se poisoning in the last 25 years. What were they all due to?
errors in formulation of nutritional supplements
- ranging from 180-1000 times the amount indicated on the bottle
Aluminium is insoluble. What can make it soluble?
decrease in pH (acidic environment)
how much aluminium is ingested daily and how much of it is actually absorbed?
ingested = 3-5 mg
absorbed = 0.02-0.1%
Aluminium is absorbed into the body by what sources
food/water
additives
utensils
medicines
- antacids
- astringents
- buffered aspirin
cosmetics/ deodorant
How is aluminum excreted from the body
majority from faeces however a small amount enters the bloodstream but leaves quickly in the urine
what is the concentration of aluminum in water and how does aluminum get into the water supply
concentration = low
aluminum sulphate is used as a flocculant in water (a substance which promotes clumping of particles to clean water supply)
The uptake of aluminum in the gut depends on what environmental factor
pH
When gut pH changes what changes about the uptake of aluminum
different forms of hydroxylated forms of aluminum
lower pH = soluble forms of Al absorbed
higher pH = insoluble forms of Al absorbed
Is Al uptake paracellular or transcellular
not known
polyvalent cations of Al is chemically similar to what other ion?
Calcium and iron
What implications do the chemical similarities between Al and calcium cause?
Al may interact with multiple types of voltage gated Ca2+ channels
- Al can inhibit/ block Ca2+ uptake in gut
- can disrupt signal transduction pathways Ca2+ is needed for
What implications do the chemical similarities between Al and iron cause?
in plasma Al can bind to transferrin instead of Fe
- taken up by peripheral tissues (through receptor mediated endocytosis) ann can accumulate in brain, liver, spleen, kidney, bone
What symptoms is aluminum toxicity associated with
renal failure
neuronal cell death
What are the symptoms of Al toxicity
motor disturbances (tremors)
seizures
visual hallucinations
dementia
coma and death
What are some non-specific symptoms of Al toxicity
muscle weakness
bone pain, osteomalacia (soft bones), fractures, premature osteoporosis
multiple non-healing issues
What is a common medical treatment which can cause Al toxicity
haemodialysis
1. can expose patient to dialysate (dialysis fluid) which is high is high in aluminum as they are used as phosphate binders (to reduce the absorption of phosphate)
- drinking contaminated water after exposure can lead to Al toxicity
2. if dialysis does not effectively remove excess Al from body it can build up over time
If serum level is above 60 mg/L what is the treatment for Al toxicity
desferrioxamine treatment or another chelating agents
- binds excess Al and will remove it through faeces or urine
