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The difference between the enzymes Synthase and Synthetase

Synthetase Icon

When studying the difference between enzymes in biochemistry the function of the enzyme usually dictates its naming convention. Even though memorizing long sequences like Glycolysis or the Citric Acid cycle involve memorizing various synthetase and dehydrogenase enzymes, most of  names used clearly state the function it carries out, and what ligand is involved.


In the Citric Acid Cycle Malate Deydrogenase clearly states that this enzyme will modify the “ligand” Malate by removing a Hydrogen atom( de-hydrogenase) and placing it on an NAD+ molecule. Just like you detach(de-tach) a poster from a wall the enzyme dehydrogenase detaches a hydrogen atom from the ligand it acts on.


Synthase vs Synthetase

As I learned more molecules I started seeing many enzymes interchange the words Synthase and Synthetase for enzymes that synthesize or create molecules. The difference between synthase and synthetase are simple. Synthetases use a high energy Nucleoside Triosphosphate such as Adenosine Triosphosphate (ATP) or Guanosine Triosphosphate (GTP) while Synthases do not.

In the urea cycle, which carries out excretion of Nitrogen waste from protein consumption,  there are synthase and synthetase enzymes present in the mitochondria of hepatocytes (liver cells). As you can see from the figure below, Carbomoyl Phosphate Synthetase I must use ATP to create Carbomoyl Phosphate. While N-acetylglutamate Synthase will create N-acetlyglutamate without the use of ATP.

Carbomoyl Phosphate Synthetase Image


Now every time you encounter an enzyme with the name Synthetase you should be able to deduce that the enzyme will not simply synthesize or create the molecule its named after, but it will most likely utilize ATP also. Enzymes that contain the phrase Synthase facilitate the creation of a molecule without using ATP.

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  9. can you please guide that the third enzyme of urea cycle i.e Arginosuccinate synthase (in many books) but uses ATP. so how this holds true for a synthase?

  10. The origional defition of synthase and synthetase made this distinction clear,but the Joint Commission on Biochemical Nimenclature said they received complaints about the similarity. Sometimes the old rule applies and sometimes this new rule applies:

    Synthase – can use nucleoside triphosohate (ATP,GTP) or not.(this is a much more broad definition)
    Synthetase – should be replaced by Ligase. Must use nucleoside triphosphate.

    The result of this change makes the naming convention more confusing since they didn’t mandate one naming system. Now synthases can be what synthetases were.

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