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)