Anaerobic Metabolism

Describe anaerobic metabolism and ketone production

Lactate

Glycolysis (also known as the Embden-Meyerhof pathway):

• Describes the conversion of glucose to pyruvate (and two ATP)
• Does not consume O₂ or produce CO₂
  Therefore it occurs in both anaerobic and aerobic conditions.
• Consumes two NAD⁺ and produces two NADH

In anaerobic conditions (in the erythrocyte, and in the setting of cellular hypoxia):

• There is no oxygen available to allow further ATP production via the electron transport chain
  There is also no regeneration of NAD⁺ in the ETC.
• In order for glycolysis to continue, NAD⁺ is regenerated via production of lactate
  $Pyruvate + NADH + H^+ \rightarrow Lactate + NAD^+$

About 1400mmol (20mmol/kg) of lactate is produced per day. Lactate is either:

• Oxidised in the cell
  This requires restoration of NAD⁺, e.g. resolution of cellular hypoxia.
• Circulated to the liver
  Lactate is then:
  • Oxidised to pyruvate
  • Converted to glucose via the Cori cycle

Ketones

Ketones:

• β-oxidation of fatty acids in the liver produces acetyl-CoA
• Acetyl-CoA usually enters the citric acid cycle to produce ATP

• When large amounts of acetyl CoA are produced, they may instead condense to form acetoacetate, which can then be reduced to β-hydroxybutyrate
  These substances are known as ketones

• Ketones can only be produced by the liver, and only used as a substrate by the kidney, as well as skeletal and cardiac muscle

• Production of ketones is accelerated by glucagon and adrenaline

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
2. ANZCA August/September 2011