It is quoted in wikipedia that:

Following the EC number classification, they belong to the group of ligases , with lyases catalysing the reverse reaction.

And we all know that enzymes are biocatalysts which catalyses reaction in both forward and backward directions.

So my question is that how can the reaction in one direction catalysed by one enzyme and in reverse direction catalysed by other enzyme? If we assume that they are telling that one direction synthase acts as ligase and in other direction it acts as lyase then how can lyases have more than one substrate for reaction? Because products(more than one) of ligase acts substrate for reverse reaction.(taking for example a ligase, glutamine synthetase as synthase)

It is also quoted from wikipedia

Lyases differ from other enzymes in that they require only one substrate for the reaction in one direction, but two substrates for the reverse reaction.

  • $\begingroup$ I am a bit confused here by your first statement, because not all enzymes are bidirectional. Most reactions which involve the breakage of an ATP or other energy molecules are not bidirectional for the same enzyme. Or even if they are it involves some sort of modulation. Next, a ligase may be a synthase but not all synthase are ligase. For me a ligase quiet literally relates to a class of enzyme related to DNA/RNA polymerization. The last question sort of relates to my statement on modulation, that if an enzyme was able to catalyze a bidirectional reaction then a checkpoint would be required... $\endgroup$ May 9, 2016 at 12:35
  • $\begingroup$ so that the enzyme does not catalyze the back reaction immediately after creating the product....so the enzyme attaches to the substrate using the lock and key model, it catalyzes the reaction, lets go of the product because the motif doesnt fit, then when the product is present in sufficient concentration it attaches to another site on the enzyme changing the binding motif so that the product is accomodated and then the back reaction is catalyzed.. $\endgroup$ May 9, 2016 at 12:37
  • $\begingroup$ Remember that Wikipedia is only as good as its contributors. It does not claim to be correct, only to be correctable. Like anyone else, I could just go in and change the entry, but I have initiated a discussion about the lyase/hydrolase question I raised in my answer, in order to try to obtain consensus before making a correction. $\endgroup$
    – David
    May 9, 2016 at 21:36

1 Answer 1


A reasonable question, but it contains a fallacy. This is because what are referred to as the forward and reverse reactions being catalysed by different enzymes are generally not, in fact, the same overall reaction.

Consider the relationship between DNA and its constituents (or RNA or Protein or fatty acid). You may be thinking of this as:

DNA ⇌ DNA constituents

But in fact, because hydrolysis (actually a hydrolase reaction) is thermodynamically favoured, synthesis of DNA (a ligase reaction) needs to be coupled to the hydrolysis of ‘high group-transfer’ deoxynucleotide triphosphates in order to shift the equilibrium in its direction. So the two reactions are (somewhat simplistically):

DNA → n dNMP (catalysed by DNases)


n dNTP → DNA + n pyrophosphate (catalysed by DNA polymerases)

Although in certain circumstances you can force reactions of this sort into reverse, in the cell they tend to be unidirectional, and are classified accordingly.

(In this sort of ligase reaction in the cell there is a further factor affecting the observed direction. That is the presence of pyrophosphatases that catalyse the thermodynamically favourable hydrolysis of pyrophosphate to orthophosphate, removing the former.)

Coda: Is the reaction in the reverse direction from a ligase necessarily catalysed by a lyase?

Although not affecting the principle expressed in my answer, I think that the latter part of the statement quoted from the Wikipedia page that “(synthases)...belong to the group of ligases, with lyases catalysing the reverse reaction” is not generally true. As mentioned above, the enzymes catalysing the reactions in the reverse direction from ligases involved in ‘polymerization’ are generally hydrolases (EC 3.1...), not lyases (EC 4...). I couldn’t immediately find an example of a lyase that fitted this description. You can peruse the links on this authoritative page if you wish to follow this up.

  • $\begingroup$ @ Koustav Pal — I see you have commented in a similar vein while I was composing this. $\endgroup$
    – David
    May 9, 2016 at 12:59
  • $\begingroup$ So, the could the summary be: Certain reactions are essentially unidirectional because of unfavourable thermodynamics in the other direction (for e.g., ATP hydrolysis or other entropic effects) or non-uniform reactant concentrations leading to skewed equilibrium? $\endgroup$
    May 9, 2016 at 13:03
  • $\begingroup$ @WYSIWYG — Yes. Probably better to add something like "especially lyase and ligase reactions)". $\endgroup$
    – David
    May 9, 2016 at 13:07
  • $\begingroup$ Just added a coda about the Wiki statement on lyases, questioning whether it should be hydrolases. Contributions welcome. $\endgroup$
    – David
    May 9, 2016 at 16:53

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