Metals in Biology

Question 1

1) Define the term ‘bacteria leaching’

Answer 1

• Making elements accessible from the geosphere to the biosphere

Question 2

2) State 4 elements present in mg/g level and 4 elements present in microgram/g level.

Answer 2

Mg/g: K > Ca >Na > Mg

Microgram/g: Zn > Fe > Cu > Sr > Se

Question 3

3) State 5/6 important uses of metals in biology

Answer 3

• Electrochemical potentials (Na and K for nerve conductions)
• Motility (Ca for muscle contraction)
• ETC and redox reactions (Mn, Cu, Fe)
• Protein structure
• Enzymatic catalysts
• Regulatory functions (signalling: Ca is a secondary messenger, Zn)

Question 4

4) State 3 examples of reactions of gases involving enzymes containing metal ions

Answer 4

• N2 -> NH3 : nitrogenase enzyme involving Fe and Mo
• H2 -> H+ : hydrogenase enzyme involving Fe and Ni
• O2 -> H2O : cytochrome C oxidase involves Fe and Cu

Question 5

5) State 3 functions of metals in proteins

Answer 5

• Catalytic enzymes
• Regulatory
• Structural (tertiary/quarternary etc)

[Also allows interactions between metals and other biomolecules]

Question 6

6) Describe 2 ways in which metal ions can be incorporated into proteins

Answer 6

• Folding of protein, then insertion of metal

- Metal present at start, assists in the protein folding (risk of misfolding leading to aggregation -> diseases)

Question 7

7) Give 3 common ligands of metals in proteins

Answer 7

• Nitrogen (histidine)
• Oxygen (glutamate, aspartate)
• Sulphur (cysteine)

[Ligands of metals can bind in many different ways which affect the properties of the protein]

Question 8

8) What is the ‘signature’ of metal-binding sites in proteins?

Answer 8

Characteristic binding patterns in a protein

Question 9

9) State 4 uses of mining sequence databases

Answer 9

• Structural genomics (structure, function, evolution, and mapping of genomes) : search for 3D structures of metalloproteins
• Determine ligand structures
• Search for homology (shared ancestry) in sequence databases
• Find putative (generally thought to exist) metalloproteins

Question 10

10) Name the 4 essential minerals (electrolytes)

Answer 10

Na, Mg, K, Ca

[Na has a high conc outside the cell and K has a high conc inside the cell]

Question 11

11) What are the requirements for Na and K per day?

Answer 11

Na: 2.3g/d
K: 4.7g/d

Question 12

12) State 2 types of complex Mg is involved in

Answer 12

• Cofactor complex (contained in every ATP complex)

- Enzyme complex

Question 13

13) Describe the function of Ca in signalling and give 2 receptors it is involved with

Answer 13

• Intracellular regulator
• Involved with tyrosine kinase and G protein-linked receptor

[Initiates pathway for inositol biphosphate formation -> binds to endoplasmic reticulum and causes release of Ca]
- Calcium ATPase used to pump Ca out of cell

Question 14

14) State the 6 essential trace metals

Answer 14

Mn, Co, Fe, Cu, Zn, Mo (forms cofactors with metals, e.g. pterin)

Question 15

15) State cofactors formed with metals, for Co, Ni and Fe

Answer 15

Co: forms Vitamin B12, cobalamin (corrin)
- only 2 reactions in human metabolism - fatty acid metabolism and folate metabolism

Ni: 9 nickel enzymes known, none in humans
Fe: present in cytochromes, myoglobin and haemoglobin

Question 16

16) State the hormone that controls iron metabolism and give the two forms iron is found in.

Answer 16

• Hepcidin controls iron metabolism (cellular export via ferroportin)
• Fe2+ (ferrous) and Fe3+ (ferric), often in redox reactions
• involved in intracellular metabolism (mitochondria, in TCA cycle)

Question 17

17) Describe the release and action of hepcidin, in response to dietary iron

Answer 17

• Dietary iron transported via plasma transferrin, to liver
• Triggers release of hepcidin which controls the number of reticuloendothelial macrophages and plasma transferrin production

[Iron loss is due to sloughed mucosal cells, desquamation (shedding outermost membrane of tissue), menstruation, other blood loss 1-2mg/day]

Question 18

18) Describe the absorption of haem and non-haem iron

Answer 18

• Via divalent metal transporter 1
• May be stored as Fe3+ (liver)
  Transported by transferrin (with glutamate/aspartate + 2xtyrosine)
• Fe is transported in ferric Fe3+ form

Question 19

19) Describe the stages of transferrin receptor (TFR)-mediated endocytosis (and leading to exocytosis)

Answer 19

1) Endocytosis: arriving Fe3+ binds to receptors on cell membrane, transferrin and Fe3+ placed inside a vesicle inside the cell
2) H+ acidifies the contents, converting Fe3+ -> Fe2+, which leaves the vesicle as ferrous
3) Vesicle containing receptors and transferrin returns to the cell membrane (recycles transferrin) via exocytosis

Question 20

20) Give 4 functions of zinc in the body

Answer 20

• All cellular processes (>3000 human zinc proteins)
• Brain function (hypothalamus for memory)
• Protection aganist toxins and toxicants
• Involved in insulin regulation (Zn is a transport protein/ carrier)
• Involved in glutamate release and mammary gland secretary vesicles (in milk)

Question 21

21) Give 3 types of disease zinc is involved in

Answer 21

• Infectious disease (immunity)
• Metabolic disease
• Degenerative and chronic disease

Question 22

22) Define ‘zinc finger motif’ and give an example of an enzyme with a zinc-binding motif

Answer 22

• Characteristic ‘signature’ binding of zinc ions
• Carbonic anhydrase (involved in pH buffering)
• Zinc finger motifs are also transcription/translation factors

Question 23

23) How and in which form does Cu enter a cell?

Answer 23

• transported via metallochaperone

- Cu2+ is first reduced to Cu+ before entering the cell

Question 24

24) Describe the use of Fe and Cu in the mitochondria

Answer 24

• in the mitochondrial respiratory chain: uses Fe in complex I (H+ pump), Fe and Cu are involved involved in cytochrome c oxidase as catalysts

[O2 + 4H+ +4e- –> 2H2O reaction]