8. Zinc Metabolism Flashcards
What are the main physiological roles of zinc?
Component of metalloenzyme:
- nucleic acid synthesis, protein digestion, protein synthesis, bone metabolism, oxygen transport, protection against free radical formation
- Zinc finger motifs - stabilised RNA/DNA
- Neuromodulator
What percentage of human proteins bind zinc?
10% (many more transport and traffic zinc)
What is ZnT3?
A zinc transporter required for accumulation of zinc in synaptic vessels - neuromodulatory role (Modulate brains excitability)
What three roles does zinc have in the brain?
- Modulates brain excitability
- Role in synaptic plasticity - learning
- Neurotoxin
What is the structure of the zinc finger motifs? What are they responsible for?
Zn(II) bound between Cys/His Amino acid centre, contains alpha helices which fit into DNA grooves.
Zinc fingers are common motifs in DNA binding proteins (transcription factors) - TF’s can wrap around DNA and use fingers to accurately bind
What is the role of zinc in fingers, twists and clusters?
Structural role.
How does zinc affect MREs (metal response elements)?
Zinc binds to MTF-1 (metal regulatory transcription factor 1) which can then bind to MRE’s and encode Zn-regulated gene
What type of acid is zinc? What reactions can it catalyse (give examples of enzymes?
A lewis acid
It may act as an acid or a base. Allowing it to activate water leading to ionisation (carbonic anhydrase) or polarisation (carboxypeptidase a). May also cause displacement of water (alkaline phosphatase)
What is the daily dietary zinc intake? Where is most zinc present in the body? Which food is most zinc present?
8-15mg a day (7-14mg excreted)
Muscle (1500mg) - least in plasma (3mg)
Meat/oysters/lobsters contains most of zinc dietary intake - 40%
Which plants contain the most zinc?
Wheat plants and seeds
Is zinc stored?
No, need to ingest enough zinc to prevent deficiency
How and where does zinc absorption take place?
In the Jejunum, transporter mediated (amount of zinc in meal will affect fractional absorption)
What happens if someone has a long term low zinc diet?
Body will adapt to absorb zinc form endogenous (within an organism) secretions in liver, pancreas or terminal regions of the small intestine
How does cellular uptake of Zinc occur?
- ZIP4 transporters take up Zn(II) into cell
2. Zinc may then be packaged into vesicles (ZnT2), stored (MT) or taken out of cell (ZnT1)
Which organs of the body is ZIP4 expression high?
Small intestine, stomach, liver, visceral yolk sac
What are the roles of ZIP and ZnT transporters? How many different ones of each are there?
ZIP - allows Zn(II) to come into cell cytosol, 14 different ones (e.g. ZIP4)
ZnT - brings Zn(II) out of cell cytosol, 10 different ones (e.g. ZnT5)
How does the transcription of metallothionein change with zinc levels?
Increased synthesis in response to high dietary zinc - due to MREs in 5’ promoter (can also bind cadmium and mercury)
What dietary characteristics would give a high zinc bioavailability?
Low in phytate and fibre, high in animal protein.
How does phytate, protein, Cu(I)/Cd(II) and Fe(II) affect zinc absorption?
Phytate: potent inhibitor of absorption
Protein: anti-phytic agent (increases absorption)
Cu(I)/Cd(II): inhibits absorption
Fe(II): inhibits absorption at supplemental levels
Give an example of three zinc deficiency caused diseases with symptoms, causes etc
Dwarfism and hypogonadism: caused by high levels of unleavened bread (flour has lots of zinc/phytates, yeast is a phytase), leads to geophagia (eating of soil…)
Acrodermatitis Enteropathica: inborn error of ZIP4 transporter gene, leads to dermatitis, dwarfism, diarrhoea, poor immunity
Mild Zn deficiency: same symptoms as above but milder
How do reduced zinc levels affect growth?
Lack of transcription factors (so less RNA synthesis, gene transcription).
Also lower zinc levels generally are caused by insufficient nutrients also
What is environmental enteropathy? How does it affect zinc levels?
A condition resulting in smaller villi (thus worse nutrient absorption leading to malnutrition and stunted growth) due to the constant faecal exposure and ingestion.
This leads to reduced zinc homeostasis which then exacerbates reduced immunity, intestinal permeability etc.
How are zinc levels assessed in the body?
Circulating zinc levels in the blood plasma are usually measured. This is not particularly accurate as high protein diet and infection can affect the readings.
Zinc in WBCs can also be measure but this is laborious.
Zinc in hair - but changes with seasons
Physiological function - but difficult to assess mild zinc deficiency
Bit of a shituation tbh
What are the dangers associated with excess zinc?
May reduce copper and iron absorption
Free zinc ions are also strong lewis acids which can dissolve in stomach acid to produce ZnCl which is bad
Name a fun fact about zinc
Zinc kills your pets
