Page 36 - Essential Haematology

22 / Chapter 2 Erythropoiesis and anaemia

The r ed c ell with haemoglobin and, as mentioned above, is
important in the regulation of haemoglobin s
’
In order to carry haemoglobin into close contact oxygen affi nity.
with the tissues and for successful gaseous exchange,

the red cell, 8 μ m in diameter, must be able: to pass

repeatedly through the microcirculation whose Hexose m onophosphate ( p entose

minimum diameter is 3.5 μ m, to maintain haemo- p hosphate) p athway

globin in a reduced (ferrous) state and to maintain
osmotic equilibrium despite the high concentration Approximately 10% of glycolysis occurs by this oxi-
of protein (haemoglobin) in the cell. Its total dative pathway in which glucose - 6 - phosphate is
journey throughout its 120 - day lifespan has been converted to 6 - phosphogluconate and so to ribulose -
estimated to be 480 km (300 miles). To fulfi l these 5 - phosphate (Fig. 2.11 ). NADPH is generated and

functions, the cell is a flexible biconcave disc with is linked with glutathione which maintains sulphy-
an ability to generate energy as adenosine triphos- dril (SH) groups intact in the cell including those
phate (ATP) by the anaerobic glycolytic (Embden – in haemoglobin and the red cell membrane.
Meyerhof) pathway (Fig. 2.10 ) and to generate NADPH is also used by another methaemoglobin
reducing power as NADH by this pathway and as reductase to maintain haemoglobin iron in the
2 +
reduced nicotinamide adenine dinucleotide phos- functionally active Fe state. In one of the most
phate (NADPH) by the hexose monophosphate common inherited abnormalities of red cells,
shunt (Fig. 2.11 ). glucose - 6 - phosphate dehydrogenase (G6PD) defi -
ciency, the red cells are extremely susceptible to
oxidant stress (see p. 79 ).
Red c ell m etabolism
Embden – Meyerhof p athway Red c ell m embrane

In this series of biochemical reactions, glucose The red cell membrane comprises a lipid bilayer,
that enters the red cell from plasma by facilitated integral membrane proteins and a membrane
transfer is metabolized to lactate (Fig. 2.10 a). For skeleton (Fig. 2.12 ). Approximately 50% of the
each molecule of glucose used, two molecules membrane is protein, 20% phospholipids, 20%
of ATP and thus two high - energy phosphate cholesterol molecules and up to 10% is carbohy-
bonds are generated. Th is ATP provides energy drate. Carbohydrates occur only on the external
for maintenance of red cell volume, shape and fl ex- surface while proteins are either peripheral or inte-
ibility. The red cell has an osmotic pressure fi ve gral, penetrating the lipid bilayer. Several red cell

times that of plasma and an inherent weakness of proteins have been numbered according to their
+
+
the membrane results in continual Na and K mobility on polyacrylamide gel electrophoresis
movement. A membrane ATPase sodium pump is (PAGE), e.g. band 3, proteins 4.1, 4.2 (Fig. 2.12 ).

needed, and this uses one molecule of ATP to move The membrane skeleton is formed by structural
three sodium ions out and two potassium ions into proteins that include α and β spectrin, ankyrin,

the cell. protein 4.1 and actin. These proteins form a hori-

The Embden – Meyerhof pathway also generates zontal lattice on the internal side of the red cell
NADH which is needed by the enzyme methaemo- membrane and are important in maintaining the
globin reductase to reduce functionally dead meth- biconcave shape. Spectrin is the most abundant and
aemoglobin (oxidized haemoglobin) containing consists of two chains, α and β , wound around each
ferric iron (produced by oxidation of approximately other to form heterodimers which then self - associate

3% of haemoglobin each day) to functionally active, head - to - head to form tetramers. These tetramers are

reduced haemoglobin. The Luebering – Rapoport linked at the tail end to actin and are attached to
shunt, or side arm, of this pathway (Fig. 2.10 b) protein band 4.1. At the head end, the β spectrin
generates 2,3 - DPG which forms a 1 : 1 complex chains attach to ankyrin which connects to band 3,