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Anaerobic Respiration

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Original Author(s): Daniel Baker
Last updated: 15th July 2023
Revisions: 20

Original Author(s): Daniel Baker
Last updated: 15th July 2023
Revisions: 20

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Anaerobic respiration is the process of ATP synthesis without adequate oxygen delivery to tissues. Sometimes the body cannot supply the muscles with the oxygen it needs to create energy, for example during intense exercise. Without the process of anaerobic respiration, there would be no energy supplied to muscles in these times of high demand.

This article will consider the process of anaerobic respiration and its clinical significance.

Process of Anaerobic Respiration

Without oxygen, the electron transport chain (ETC) cannot continue as there is no terminal electron acceptor. Therefore, the usual number of ATP molecules cannot be created. Cessation of the ETC leads to reduced activity of the reactions before this step, such as the TCA cycle and glycolysis. The anaerobic pathway utilises pyruvate, the final product of glycolysis.

Without the functioning ETC there is an excess of NADH and pyruvate. Pyruvate is subsequently reduced to lactate (lactic acid) by NADH, yielding NAD+. This reaction is catalyzed by the enzyme lactate dehydrogenase. By recycling NAD+, the process of glycolysis is able to continue as the supply of NAD+ has been replenished. Glycolysis produces 2 net ATP molecules, which can be used for energy.

Fig 1 – Diagram showing the process of anaerobic respiration

While these 2 ATP molecules are much less than would be produced by aerobic respiration, without anaerobic respiration there would be no other method of ATP production. Anaerobic glycolysis happens faster than aerobic because less energy is produced for every molecule of glucose broken down (2ATP vs 32ATP), so more glucose must be broken down at a faster rate to meet energy demands.

In situations where cells’ oxygen demands increase above supply (i.e. ischaemia), glycolysis will quickly occur, producing lactic acid. This may occur physiologically, such as in the muscles during intense exercise, or pathologically, for example in ischaemic heart disease or when a malignant tumour outgrows its blood supply.

Removal of lactate

The lactate produced as a result of anaerobic respiration must be removed from the blood as it is acidic. There are two main ways to do this:

  • Lactate is transported to metabolically active cells, such as in the heart and brain. Here it is converted back to pyruvate, which is then utilised in the TCA cycle.
  • Lactate is transported to the liver and converted to pyruvate. Pyruvate is then used in the process of gluconeogenesis to create more glucose

Clinical Relevance – Lactic acidosis

Excessive production of lactate can lead to lactic acidosis, a sub-type of metabolic acidosis. This is where the pH of the blood has become more acidic due to rising levels of lactate within the body. There are a number of causes for lactic acidosis but broadly it is caused by the body being unable to respire aerobically. Some causes include:

  • Diabetes mellitus
  • Enzyme deficiencies – for example, pyruvate dehydrogenase deficiency
  • Drugs – for example, metformin and isoniazid
  • Haemorrhage
  • Sepsis
  • Mitochondrial disorders

Symptoms typical of metabolic acidosis include nausea, vomiting, muscle weakness and rapid breathing. Treatment is difficult, as there is little evidence to support the use of sodium bicarbonate solutions (to balance the pH) or direct removal of lactate (via haemofiltration). Treatment is therefore supportive and would depend on the aetiology; if medication is the cause it may need to be withdrawn and certain mitochondrial disorders may require adapted diets.