Carriage of Oxygen in the Blood Flashcards
What are the two jobs of the cardiovascular system?
- Supplies oxygen and metabolic fuel (e.g. glucose) to tissues and takes away waste products of metabolism (e.g. CO2)
- Maintains defences against invading microorganisms
Why is carriage of oxygen important?
As oxygen is a powerful oxidising agent:
o Most organic molecules are damaged by too high concentration of O2
o Erythrocytes are specially designed to carry this dangerous cargo
What is oxidation?
Oxidation = loss of electrons
Oxidising agents like molecular oxygen are ‘electron hungry’ so, when they combine with other atoms or molecules, they remove electrons from the oxidised molecule
Oxidation simplifies electronic structure of the substrate, thus decreasing the free energy of the system and releasing energy, often in the form of heat
What is reduction?
In contrast, reduction adds electrons, often building more complex molecules from simpler ones
Reduction usually requires energy
Give an example of oxidation.
Fe++ -> Fe+++ + e¯
When might an oxidation be irreversible or reversible?
When oxidation release a large amount of energy at once, the reaction is generally irreversible (e.g. an explosion) – the electron cannot be ‘handed back’ by the oxidised compound
On the other hand, if the electron transfer only involves a small amount of energy, the reaction may be reversible
What is an important example of a reversible oxidation?
A good example (remember this) is the reaction between oxidised and reduced nicotinamide adenine dinucleotide (NAD):
NAD+ + H+ + 2e- NADH
(oxidised low energy form reduced high energy form)
The NAD+/NADH can be thought of like a bank with electrons as money
The bank can loan another molecule money (NADH can give up electrons and becomes NAD+) or a molecule can save money by storing electrons (by giving up electrons to NAD)
This system is involved in very many reactions that involve electron transfer in the body.
How do red blood cells allow for effective carriage of oxygen?
To be useful, an oxygen carrier must be able to bind oxygen reversibly
Haemoglobin is a unique molecule as it can combine rapidly and reversibly with oxygen without becoming oxidised
Found in erythrocytes
Normal erythrocytes are biconcave disks about 7 µm in diameter and about 2 µm thick
They have a volume of about 90 cu mm (1 cu mm = 1 femtolitre)
A typical erythrocyte contains about 270 million haemoglobin molecules
The sizes of red cells can vary in several common illnesses: for example, if a red cell is smaller than usual- this occurs in microcytic anaemia
If a red cell is larger than normal- this is macrocytic anaemia
Mature red cells have no nuclei or mitochondria!
This may be because mitochondria or DNA are easily damaged by the high oxygen levels found in erythrocytes
Why is it difficult for mature red cells to get energy? Why do they need ATP?
Because they have no mitochondria, the mature red cells cannot get energy by oxidative metabolism
However, they do require ATP to maintain the sodium pumps in their cell membranes and for other ion pumping operations
How do red cells produce ATP?
Red cells produce ATP by glycolysis: (this is conversion of glucose to pyruvate followed by conversion of pyruvate to lactic acid - it is less efficient than aerobic metabolism)
Thus, red cells have a naturally low pH
How do red cells take up glucose?
- Red cells have a different glucose uptake system (Glut1) to other cells in the body: Glut1 works by facilitated diffusion and this uptake is not regulated by insulin
How and why do red cells produce NADPH?
Red cells also use the pentose phosphate pathway to generate NADPH
NADPH helps counteract the oxidative stress on the cell by the very high pO2
How do red cells protect themselves against oxidative damage? What kind of damage might they experience?
Red cells contain antioxidants (eg Vitamin C & glutathione) to protect them against oxidative damage (this is also taken up from the blood by Glut1)
However, they are progressively damaged by the oxygen they carry
The haemoglobin is gradually converted to methaemoglobin (oxidised haemoglobin)
The lack of repair ability means that the red cells have a limited lifetime; typically about 120 days
The aging erythrocyte undergoes changes in its plasma membrane, making it susceptible to recognition by phagocytes and subsequent phagocytosis in the spleen, liver and bone marrow
