Methaemoglobin (MetHb)

In MetHb,

Iron is ferric (Fe3+) instead of ferrous (Fe2+)

Characteristics

• Dark coloured
• Unable to combine with oxygen
• Causes cyanosis when MetHb > 1.5g/dL
  * Cyanosis only occurs when DeoxyHb > 5g/dL
• Normally MetHb is about 1-2% of total Hb
  * ?? Reference

Formation

• When oxyhaemoglobin acts as nitric oxide (NO) scavenger
• Drugs
  * e.g. prilocaine, benzocaine, nitrites, dapsone

Reduction

Iron is reduced back to ferrous
--> MetHb converted back to Hb

By 4 systems:

1. NADH-methaemoglobin reductase system

• Present in RBC
• Uses NADH provided by Embden-Meyerhof pathway
• Accounts for 2/3 of MetHb-reducing activities
• Deficient in familial methaemoglobinaemia

2. Ascorbic acid

May slowly reduce the iron by direct chemical effect

Accounts for 16% of MetHb reduction

3. Glutathione-based reductive enzymes

Small amount of MetHb reductase activity

4. NADPH-dehydrogenase enzyme in RBC

• Can reduce MetHb using NADPH from pentose phosphate pathway
• Under normal condition, this system has almost no effect
• Regarded as a reserve mechanism

NB:

[KB2:p137]

In presence of methylene blue, activity of NADPH-MetHb reductase (?? same as NADPH-dehydrogenase) increases
--> NADPH-MetHb reductase reduces methylene blue
--> Reduced form of methylene blue reduces MetHb