14.5 The Respiratory Balance Sheet

It is possible to make calculations of the net gain of ATP for every glucose molecule oxidised; but in reality this can remain only a theoretical exercise. These calculations can be made only on certain assumptions that:

• There is a sequential, orderly pathway functioning, with one substrate forming the next and with glycolysis, TCA cycle and ETS pathway following one after another.

• The NADH synthesised in glycolysis is transferred into the mitochondria and undergoes oxidative phosphorylation.

• None of the intermediates in the pathway are utilised to synthesise any other compound.

• Only glucose is being respired – no other alternative substrates are entering in the pathway at any of the intermediary stages.

But this kind of assumptions are not really valid in a living system; all pathways work simultaneously and do not take place one after another; substrates enter the pathways and are withdrawn from it as and when necessary; ATP is utilised as and when needed; enzymatic rates are controlled by multiple means. Yet, it is useful to do this exercise to appreciate the beauty and efficiency of the living system in extraction and storing energy. Hence, there can be a net gain of 38 ATP molecules during aerobic respiration of one molecule of glucose.

Now let us compare fermentation and aerobic respiration:

• Fermentation accounts for only a partial breakdown of glucose whereas in aerobic respiration it is completely degraded to CO2 and H2O.

• In fermentation there is a net gain of only two molecules of ATP for each molecule of glucose degraded to pyruvic acid whereas many more molecules of ATP are generated under aerobic conditions.

• NADH is oxidised to NAD+ rather slowly in fermentation, however the reaction is very vigorous in case of aerobic respiration.

14.6 Amphibolic Pathway

Glucose is the favoured substrate for respiration. All carbohydrates are usually first converted into glucose before they are used for respiration. Other substrates can also be respired, as has been mentioned earlier, but then they do not enter the respiratory pathway at the first step. See Figure 14.6 to see the points of entry of different substrates in the respiratory pathway. Fats would need to be broken down into glycerol and fatty acids first. If fatty acids were to be respired they would first be degraded to acetyl CoA and enter the pathway. Glycerol would enter the pathway after being converted to PGAL. The proteins would be degraded by proteases and the individual amino acids (after deamination) depending on their structure would enter the pathway at some stage within the Krebs’ cycle or even as pyruvate or acetyl CoA.

Since respiration involves breakdown of substrates, the respiratory process has traditionally been considered a catabolic process and the respiratory pathway as a catabolic pathway. But is this understanding correct? We have discussed above, at which points in the respiratory pathway different substrates would enter if they were to be respired and used to derive energy. What is important to recognise is that it is these very compounds that would be withdrawn from the respiratory pathway for the synthesis of the said substrates. Hence, fatty acids would be broken down to acetyl CoA before entering the respiratory pathway when it is used as a substrate. But when the organism needs to synthesise fatty acids, acetyl CoA would be withdrawn from the respiratory pathway for it. Hence, the respiratory pathway comes into the picture both during breakdown and synthesis of fatty acids. Similarly, during breakdown and synthesis of protein too, respiratory intermediates form the link. Breaking down processes within the living organism is catabolism, and synthesis is anabolism. Because the respiratory pathway is involved in both anabolism and catabolism, it would hence be better to consider the respiratory pathway as an amphibolic pathway rather than as a catabolic one.