8. Zinc Metabolism

Question 1

What are the main physiological roles of zinc?

Answer 1

Component of metalloenzyme:

1. nucleic acid synthesis, protein digestion, protein synthesis, bone metabolism, oxygen transport, protection against free radical formation
2. Zinc finger motifs - stabilised RNA/DNA
3. Neuromodulator

Question 2

What percentage of human proteins bind zinc?

Answer 2

10% (many more transport and traffic zinc)

Question 3

What is ZnT3?

Answer 3

A zinc transporter required for accumulation of zinc in synaptic vessels - neuromodulatory role (Modulate brains excitability)

Question 4

What three roles does zinc have in the brain?

Answer 4

1. Modulates brain excitability
2. Role in synaptic plasticity - learning
3. Neurotoxin

Question 5

What is the structure of the zinc finger motifs? What are they responsible for?

Answer 5

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

Question 6

What is the role of zinc in fingers, twists and clusters?

Answer 6

Structural role.

Question 7

How does zinc affect MREs (metal response elements)?

Answer 7

Zinc binds to MTF-1 (metal regulatory transcription factor 1) which can then bind to MRE’s and encode Zn-regulated gene

Question 8

What type of acid is zinc? What reactions can it catalyse (give examples of enzymes?

Answer 8

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)

Question 9

What is the daily dietary zinc intake? Where is most zinc present in the body? Which food is most zinc present?

Answer 9

8-15mg a day (7-14mg excreted)

Muscle (1500mg) - least in plasma (3mg)

Meat/oysters/lobsters contains most of zinc dietary intake - 40%

Question 10

Which plants contain the most zinc?

Answer 10

Wheat plants and seeds

Question 11

Is zinc stored?

Answer 11

No, need to ingest enough zinc to prevent deficiency

Question 12

How and where does zinc absorption take place?

Answer 12

In the Jejunum, transporter mediated (amount of zinc in meal will affect fractional absorption)

Question 13

What happens if someone has a long term low zinc diet?

Answer 13

Body will adapt to absorb zinc form endogenous (within an organism) secretions in liver, pancreas or terminal regions of the small intestine

Question 14

How does cellular uptake of Zinc occur?

Answer 14

1. 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)

Question 15

Which organs of the body is ZIP4 expression high?

Answer 15

Small intestine, stomach, liver, visceral yolk sac

Question 16

What are the roles of ZIP and ZnT transporters? How many different ones of each are there?

Answer 16

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)

Question 17

How does the transcription of metallothionein change with zinc levels?

Answer 17

Increased synthesis in response to high dietary zinc - due to MREs in 5’ promoter (can also bind cadmium and mercury)

Question 18

What dietary characteristics would give a high zinc bioavailability?

Answer 18

Low in phytate and fibre, high in animal protein.

Question 19

How does phytate, protein, Cu(I)/Cd(II) and Fe(II) affect zinc absorption?

Answer 19

Phytate: potent inhibitor of absorption

Protein: anti-phytic agent (increases absorption)

Cu(I)/Cd(II): inhibits absorption

Fe(II): inhibits absorption at supplemental levels

Question 20

Give an example of three zinc deficiency caused diseases with symptoms, causes etc

Answer 20

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

Question 21

How do reduced zinc levels affect growth?

Answer 21

Lack of transcription factors (so less RNA synthesis, gene transcription).

Also lower zinc levels generally are caused by insufficient nutrients also

Question 22

What is environmental enteropathy? How does it affect zinc levels?

Answer 22

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.

Question 23

How are zinc levels assessed in the body?

Answer 23

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

Question 24

What are the dangers associated with excess zinc?

Answer 24

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

Question 25

Name a fun fact about zinc

Answer 25

Zinc kills your pets