Week 7: Trace Elements Flashcards
What is carbonic anhydrase?
Family of enzymes
Regulates CO2 in cell (traps it as bicarbonate)
Catalyses:
H2O + CO2 → H+ + HCO3-
Reversible reaction that occurs relatively slowly in the absence of a catalyst
Active site of most carbonic anhydrases
-Contains a zinc ion
= metalloenzymes
What is a zinc finger?
- Transcription Factor
- small protein structual motif
- coordination of one ore more zinc ions used to stabilize a fold
What are the physiological roles of zinc?
Nucleic acid metabolism
• DNA synthesis and transcription
• Gene regulation
Signalling
• Regulates activity of cAMP and cGMP
• Activates protein kinase C
• Brain, affects NMDA and GABA receptor activity
• Hepatocytes releases calcium from intracellular stores
Extracellular matrix
• Required for activity of MMPs (matrix metalloproteinases)
Membrane function
• Required for membrane stability
Lipid metabolism
How does zinc influence synaptic function? (1)
Zinc released from the presynaptic neuron and can act on several receptors on the postsynaptic neuron
How does zinc influence synaptic function? (2)
-May diffuse to nearby glial cells
- inhibit EAAT-1 (glutamate transporter)
- increasing amount of glutamate (neurotransmitter)
present in synapse (more glutamate for other receptors)
How can Zinc cause brain cell death? and what is the treatment?
In traumatic brain injury/ zinc deficiency (e.g. stroke) there is a release of high levels of zabile zinc in degenrating neurons after brain injury.
Zinc is then released into extracellular environment= cell death
Treatment is zinc chelator > reduces cell death
How is zinc important element of apoptotic pathway?
- Cytosolic labile zinc is increased in apoptotic brain cells
- Cytosolic zinc accumulates in apoptotic brain cells during development
- Again, use of zinc chelator injected into rats after birth decreases number of apoptotic cells
How much zinc is required per day?
10mg
What are the effects of nutritional zinc deficiency?
•Neuropsychiatric effects, depression
• Dermatitis
• Diarrhoea
• Alopecia - spot baldness
• Anorexia
• Impaired taste
• Reduction in immune function
• Infections
• Delayed puberty
What are some conditions in which predispose individuals to nutritional zinc deficiency?
• Inadequate intake and absorption of zinc
− Inflammatory bowel disease, biliary obstruction, liver
disease, renal failure
• Malnutrition
• Vegetarianism in combination with poor overall diet
• Therapeutic and synthetic diets (diet with not enough nutrients
E.g. enteral and parenteral nutrition, and diets for
management of inborn errors of metabolism
• Intestinal infestation (bacteria, protozoa, helminths) (these can stop you from absorbing zinc
• Nutrient interactions with dietary components and drugs
− E.g. diuretics and antibiotics
Name an inherited zinc deficiency
Acrodermatitis enteropathcia
What is acrodermatitis enteropathcia? Name also symptoms and characterisation
Rare genetic disorder autosomal recessive
- Mutation in protein (SLC39A4: zinc uptake
transmembrane protein
• Characterised by:
− Skin inflammation (dermatitis); inflammatory rash
around the mouth and/or anus
− Diarrhoea
− Hair loss (alopecia)
• Malabsorption of zinc through intestinal cells
• Symptoms usually occur:
− Bottle-fed infants: a few days or weeks after birth
− Breast-fed infants: soon after weaning
• Zinc deficiency in premature breast fed babies due
reduced zinc levels of mother’s milk
What is the treatment for zinc deficient baby?
IV infusion of zinc e.g. zinc chloride
Regular IV infusions of zinc
What is the function of zinc transporters? Where are they located?
Deliver zinc to cell and intracellulr organelles
Transporters located in”
- Plasma Membrane
- Intracellular membranes
What are the two main families of zinc?
• Solute carrier 30 (SLC30) [aka Znt, 10 in family]
• Solute carrier 39 (SLC39) [aka ZIP, 14 in family]
− (mutations cause Acrodermatitis enteropathica)
Function of Zinc transport (ZnT) or solute carrier 30 (SLC30) family
Controls the efflux of zinc from the cytoplasm out of the cell and from the cytoplasm into vesicles
Function of Zinc importer (ZIP) or solute carrier 39A (SLC39A) family
Controls the influx of zinc into the cytoplasm from outside of the cell and from vesicles.
What are the benefits of Zinc supplemation?
• Reduces duration and severity of diarrhoea in
malnourished children
• Reduces duration and severity of common cold (immune
system effect)
• May prevent macular degeneration
What are symptoms of zinc toxicity?
• Nausea and vomiting
• Gastric and oesophageal bleeding
• Dizziness
• Lethargy
• Fever
• Copper deficiency (competes with copper for binding in RBC
- (metallothionein binding in enterocytes)
• Anaemia
• ‘Metal Fume Fever’
- Welders exposed to zinc oxide fumes
-Flu-like symptoms
-tolerance can develop, although transient
How much iodine is needed a day?
150micrograms intake/day
Function of iodine
Only confirmed function= substrate for thyroid hormone synthesis
Foods that have iodine
Dairy products, seafood, seaweed (kelp), eggs, bread, some vegetables
Physiological use of iodine (thyroid)
Follicular cells of thyroid gland
- Produce thyroid hormones T4 and T3
T3- tri-iodothyronine
T4- thyroxine
Synthesised from: tyrosine in combination with iodine
T4 converted to T3 at target tissue
Thyroid hormones enter all cells and bind to nuclear receptors
− Thyroxine-binding receptors: regulate gene
transcription
− Increase metabolic activity
− Stimulate synthesis of mitochondrial enzymes and
increase mitochondrial activity
What is a follicle in a thyroid gland?
Structural and functional units
Major thyroid secretory cells arranged into hollow spheres
- Each sphere forms a functional unit called a follicle
What is a colloid?
Storage site for thyroid hormones
- Serves as an extracellular storage site (and production) of thyroid hormones
What are C cells?
Secrete calcitonin in which regulates calcium level in the blood
List the thyroid hormone synthesis and action in order
Thyrotropin-releasing
hormone (TRH) secreted
from the hypothalamus
stimulates thyroid
stimulating hormone
Thyroid stimulating
hormone (TSH) made in the
anterior pituitary gland
Thyroid stimulating
hormone regulates T3 and
T4 synthesis in the thyroid
gland
Step by step of synthesis of thyroid hormones
- Thyroglobulin is synthesized in the rough ER, and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.
- Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I−) actively into the cell
- Iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner
4 In the collloid, iodide (I-) is oxidized to iodine (I0) by an enzyme called thyroid peroxidase
Iodine (I0) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (approx. 120 tyrosyl residues in total).
- In conjugation, adjacent tyrosyl residues are paired together
- Thyroglobulin re-enters the follicular cell by endocytosis (T3 and T4 attached)
- Proteolysis by various proteases liberates thyroxine and tri-iodothryonine molecules. Then enter in blood supply
What happens if there is no TSH?
Thyroid atrophies (shrinks)
Consequence: hormones released at very low rate
What happens if too much TSH?
thyroid gland hypertrophies
What are the long term effects of iodine deficiency? Include symptoms
Thyroid gland adapts to insufficient supply by increasing trapping
• Increase size of gland = Goitre
(overgrowth of gland)
• Not enough thyroid hormone is
produced = Hypothyroidism
Symptoms: dry skin, hair loss,
decreased metabolic rate =
fatigue/lethargy and slowed
reflexes, constipation
What is goitre?
Enlargement of thyroid
Most are benign
Effects of iodine deficiency in children
In children
• Congenital Iodine deficiency
− Cretinism
− Hypothyroidism with decreased function
of thyroid
• slowing down of mental and
physical activity
• thickening and drying of skin
• Dwarfism
• Mental retardation
• Goitre not present
What are the symptoms of iodine toxicity?
Burning of mouth, throat, and stomach, fever, nausea, vomiting, diarrhea, a weak pulse, cyanosis, and coma
What is wolff-chaikoff effect?
an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones.
