Lecture Twenty Four - Oxygen transport in organisms Flashcards
How does CO binding have a toxic effect?
Carbon monoxide (CO) is toxic due to its binding to heme 200 times more strongly than oxygen.
Thus oxygen uptake and transport is prevented.
Since both CO and O2 binding is an equailibrium process, CO binding can be reversed by breathing in high concentrations of oxygen.
Air contains ~20% oxygen and 0.1% CO, [HbO2] = [HbCO].
When CO binds to haem, the Fe oxidation state is 2+, whereas when O2 binds to haem, the Fe oxidation state is 3+.
What is haemocyanin?
Haemocyanins are oxygen carrying copper containing proteins.
Found in molluscs and anthropods i.e. crabs, snails, scorpions and spiders.
Blue blood from Cu(II) binding to O2.
Use Cu ratehr than Fe.
Horseshoe crab:
Super blue blood = ~15,000 per litre.
Super antibacterial properties.
Special clotting agent that stops infection.
Active site it make up of two Cu(I) centres coordinated to three histadine residues each.
Cu has no prosthetic group.
Just uses three His groups.
Instead of one Fe, there are two Cu being held close to one another with three His on each.
When oxygenated, there are two oxygens being held in between the coppers.
Copper is 1- when de-oxygenated and 2- when oxygenated.
What are Zinc based enzymes?
Zinc (Zn2+) is present in over 200 enzymes.
A 70kg human has bout 2.3g in their body.
No redox chemistry with Zn2+.
Hard metal - likes N and O donors (O more labile than N).
Strong lewis acid.
Coordnation number - 4 (but can be 5).
Standard coordination envrionmnets: Fixed geometries - tetrahedral.
Explain carbonic anhydrase.
Found predominantly in red blood cells.
Catalyses the reaction of the reversible hydration of carbon dixoide to form the bicarbonate ion and a proton.
CO2 + H2O <–> H2CO3 <–> HCO3- + H+ <–> CO32- + H+.
Rate of forward reaction (Kf) = 0.15 s^-1.
Rate of back reaction (Kb) = 50.0 s^-1.
That is, the forward reaction is much quicker.
Active site has three His molecules bounded by a Zn molecule.
Need water to be coordniated to the Zn for reaction to occur.
Zn is not consumed, but is needed to have the reaction proceed.
Enzyme increases reaction rate ~10^7 at physiological pH - (10^7 reactions per second).
Carbonic anhydrases play important roles in, for example:
- Photosynthesis (rapid uptake of CO2).
- Respiration (rapid disposal of CO2).
- pH control (buffering).
What is cis-platin?
Some metals are used therapeutically, coordinating to biological ‘ligand’ molecules.
Cis-platin is an anti-cancer drug in which the metal ion Pt binds to DNA preventing replication.
Historically:
Rosenberg (1968) - retarded E.coli bacteria growth by applying a current with Pt electrods - low levels of cis-platin were found.
- Effective for bladder and cervical tumors, ovarian and testicular cancers.
- Side effects = nausea and kidney damage.
Square planar complex.
Mode of action:
1) After intravenous injection, cis-platin travels through blood stream ([Cl-] ~0.1M) unchanged and is transported across membrane into the cell.
2) In cells, [Cl-] is low, cis-platin hydrolyses to the active diaqua ion (NB: now a charged complex).
3) Drug binds to the DNA bases, preventing transcription.
[Pt(NH3)2Cl2 <–> [Pt(NH3)2(OH2)Cl]+ <–> [Pt(NH3)2(OH2)2]2+
With Cl- written above the arrows (have a look at the photo you took on your phone of this reaction).
The diaqua form then reacts adjacent guanine residues and causes the unwinding of the DNA duplex and inhibits replication.
