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Inactivation of haemoglobin

2+
Oxygen binding to haemoglobin can only occur if the Fe site directed towards the
distal His is accessible. There are specific mutations where this is not the case, such as in the
so-called Boston-Hb, where the distal His is replaced by Tyr, the tyrosinate-oxygen of which
tightly coordinates to the iron site and thus blocks off access of O 2. Carbon monoxide exerts a
comparable effect, which is responsible for the toxicity of CO. CO is bound 220 times more
2+
strongly to Fe than O 2: 0.25% of CO in air, i.e. the CO contents of inhaled cigarette smoke of
20 cigarettes per day, block off about 25% of the oxygen binding capacity of Hb. NO (formed
by reduction of nitrite) has a comparable effect

The naturally occurring mutant Glu6Ala (glutamate at position 6 exchanged for alanin)
causes sickle cell anaemia, a deformation of the red blood cells by polymerisation of the globin
subunits of Hb. The blood of people suffering from sickle cell anaemia has restricted O 2
capacity. These people are, however, immune against malaria, which has led, by selection, to a
high percentage of anaemic individuals amongst the populations of some tropical African
regions.

A certain amount of haemoglobin is consistently oxidised to methaemoglobin (MetHb)
by oxidants such as peroxide, hyperoxide and OH radicals:

+
2+
3+
-
Hb(Fe ) + H 2O → MetHb(Fe -OH) + e + H

-
Met-Hb, in which the second axial position is blocked by OH is, however, consistently
”repaired“ by methaemoglobin-reductase (containing NADH as cofactor).

Oxygen transport by haemocyanins and haemerythrin

Hemocyanins are oxygen transport proteins occurring in arthropods (spiders, crabs,
lobsters, …) and molluscs (snails, squids, …). They contain a dinuclear copper centre per
subunit. Molecular weights vary from 450 kDa (arthropods, subunits of 75 kDa) to 9 MDa
(molluscs, subunits of 50-55 kDa). The oxygen is reversibly taken up by oxidative addition:

2+
+
2+
2-
O 2 + {Cu 2} ' {Cu (µ-O 2 )Cu

2
2
The peroxide thus formed coordinates in the unusual side-on bridging mode, µ-η :η ; Fig. 8).
HN NH HN NH
N N N I I O N I I NH
I I NH N
HN N Cu Cu N + O 2 HN N Cu O Cu

N N - O 2 N N

NH NH NH NH

Figure 8. Reversible uptake and release of oxygen by haemocyanins.

An oxygen transport protein occurring in certain non-segmented worms (the sipunculid
family) is haemerythrin, consisting of eight subunits (overall molecular weight 108 kDa), each
of which containing a dinuclear iron centre; Fig. 9. In the desoxy form, these are ferrous
-
centres, bridged by OH , an aspartate and a glutamate. One of the iron centres is additionally