Lecture Twenty Three - Haemoglobin and myoglobin in relation to inorganic chemistry Flashcards
What uses do metal ions have in biology?
Biology uses metal ions and lighands to form complexes with many functions.
Na+, K+ and Mg2+ = Osmotic control, nerve action and enzymes (Mg2+_.
Ca2+ = Structurals (bones, teeth, shells), triggering action (muscles).
Trace metal ions - are also essential in very small amounts.
V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo.
Bioinorganic chemistry uses the principles of coordination chemistry to understand how biological coordination complexes function.
Explain amino acids and proteins with regards to transition metals.
Amino acids and proteins are a major source of ligands.
The side chains of these amino acid residues can be acidic, basic or neutral.
What are prosthetic groups?
Some proteins have non-amino acid or prosthetic groups present in the protein, which are essential for protein activity.
If the prosthetic group contains a metal ion the protein is called a metalloprotein.
E.g. Haemoglobin (Hb) and myoglobin (Mb) which both have an Fe contining haem prosthetic group.
Explain Hb and Mb and oxygen transport.
Mb and Hb are haem-iron proteins that transport oxygen around the body.
Mb = MWt ~ 12,000; is a single polypeptide (152aa long).
Hb = A tetramer (four polypeptides make up this molecule), MWt ~ 64,500.
Mb and each unit of Hb have a haem prosthetic group which is the active site that binds oxygen.
Hb transports oxygen in the blood of mammals.
Mb carries the oxygen to the muscles.
The haem is connected to the protein via a His nitrogen.
I.e. coordinated to the Fe centre. This leaves a vacent coordination site for oxygen binding and transport.
What is the structure of haemoglobin?
Four subunits each containing a haem unit.
The structure of the haem unit is in the rest state.
The Fe (II) centre is coordinated by a protoporphyrin IX ligand and a histidine reside, the non-terminated stick represents the connection to the protein backbone.
Hydrogen atoms are omitted for clarity.
Describe myoglobin.
Overall reaction:
Deoxy-Mb + oxygen <–> Oxy-Mb.
High spin Fe(II):
Fe2+ lies ~40pm out of haem plane (towards the His).
Fe2+ in square pyramidal geometry, ‘resting state.’
Reversible:
Redox reactions:
Fe^2+ –> Fe^3+ (Fe^2+ = high spin, Fe^3+ = low spin).
O2 –> O2^-. (O2^-. is radical).
Low spin Fe (II):
Fe3+ lies in the plane, pulling the His with it.
Fe 3+ in octahedral geometry.
Fe-O2 is diamegnetic.
Diamagnetic because spins on each molecule add together to have one free electron.
The unpaired electron of Fe is coupling with the unpaired electron on oxyhen and they cancel one another out therefore making it diamagnetic.
What are the characteristics of oxy-Mb?
If oxy-Mb is diamagnetic, how do we distinguish between:
(i) A neutral oxygen coordination to Fe(II).
(ii) O2^-. (superoxide) coordination to Fe(II).
Infrared spectroscopy:
Analyse v(O_O) streching frequencies.
Superoxide O2^-. ~ 1140cm^-1.
O2^2- ~ 800 cm^-1.
Neutral O2 ~ 1560cm^-1.
In oxy-Mb/oxy-Hb observe:
V(O_O) 1107 (Hb) and 1103 cm^-1.
So, the oxygen ligand binds as superoxide.
Note - Both Fe (III) and O2^-. have an unpaired electron, so these must pair in the complex = diamagnetic.
Draw a diagram of the simple bonding model for oxy-Mb.
What ligand based analysis can be used?
In Mb/Hb, Fe haem attaches to protein via the histidine N donor atom.
O2 binds to the reduced Fe and a redox reaction occurs, i.e. an electron is transferred.
Oxygen binds end-on, in a bent manner and is protected in a cavity within the protein.
As oxygen is released, this reaction is reversed.
Oxygen transfers from haemoglobin to myoglobin, due to a stronger affinity for dioxygen than haemoglobin, at low oxygen levels.
