# How to predict amine donor in biochemical reactions (whether glutamine or aspartate)?

In biochemical reactions amine $$(\ce{-NH2})$$ transfer is done in multiple pathways (e.g. urea cycle, purine biosynthesis etc.).

In many of the situations glutamine donates amine group (e.g. xanthosine monophosphate → guanosine monophosphate). In few instances, however, aspartate donates amine $$(\ce{-NH2})$$ group (e.g. inosine monophosphate → adenosine monophosphate).

This seems to be very random to me. Is there any pattern in such amine transfer reactions? Can we generalise it in some way?

• While that's on topic here, you may have better chances with similar questions on Biology.SE. – Mithoron Aug 14 at 17:56
• The answer to this question might be "whichever residue is at the appropriate location in the enzyme's active site". – Ben Norris Aug 16 at 15:39
• The side chain or aspartate cannot DONATE an amine (-NH2) as it does not have one.. Only the side chains of asparagine (N) and glutamine (Q) in addition to Lysine (K), and argentine (R) have amine groups.. (and not all of them are capable of donating due to resonance).. Unless aspartate is the substrate (i.e. freely bound) – CuriousTree Sep 7 at 6:35
• Go through purine de novo biosynthesis. You will see where Aspartate reacts to transfer an amine to the substrate. And I never saw a biosynthetic pathway where Asparagine donates amine group. – A.N. Ψ Sep 8 at 7:21
• @A.N.Ψ, I can see that I misinterpreted the question a bit, as I was automatically thinking of amino-acid side chains in protein. However, if the aspartate is on its own (as a substate) then I can see how this is the case. I.e. the -NH3 group may be donated.. I think I should update my answer a bit in this regard. – CuriousTree Sep 9 at 14:24

There are several very general concepts that you have to know about in order to see a pattern in biochemical reactions driven by enzymes. A quick answer is given at the very end. Amongst many concepts to understand, two main concepts are as following:

Enzyme are classified with a specific enzyme commission (EC) number, which is a type of ID number based on catalytic function. The first number groups the enzyme into an overall group. In example, enzymes that can transfer functional groups are placed in EC.2. Within EC.2 you can then subdivide into more specific functions, e.g. transaminases that transfer nitrogen containing groups have the the EC number of 2.6, and within this group again you can find enzyme that specifically transfer amine groups. Those enzymes will then have the EC number of 2.6.1 (aminotransferases), and you can then further specify into families, e.g. aspartate aminotransferases EC.2.6.1.1.

Enzymes folds within specific functional families is evolutionary conserved and highly specific. The three-dimensional shape of enzymes within a specific family, e.g. aspartate transaminase; EC 2.6.1.1, is very conserved (the amino acids sequence identity will also be very high) and enzymes that are grouped into the same family will have highly similar overall structure and thus very similar mechanisms of catalysing reactions. In contrast, enzymes in completely different families, with different foldes and different amino-acid sequence will have completely different catalytic mechanisms.

To predict how some enzyme will catalyse a reaction, you need to find what enzyme it is related to. Here it will also be important to remember that structure is more conserved than sequence. A good starting point is to do a BLAST search with the protein sequence that you are investigating, note the you could also do a blast search against the PDB database to find related published protein structures.

Continuing with the exsample of amino-transferases, you can even subdivide the enzymes into where the catalytic reaction will take place. In example, you have alpha-aminotransferases or omega-aminotransferases, depending on the location on the substrate that the amino will we translocated to and from.

To answer your question: Now that we covered some very general concepts about enzymes, it is important to know that their structure and sequence are specifically designed to accommodate a particular substrate. In other words, some enzymes will take aspartate as substrate and donate its amine group - while other type of enzymes will take glutamine as substate - and donate its amine group.

As a side-note. In proteins, the amine-group in aspartate would be part of the protein backbone (amide bond / peptide bond), and the side-chain (no amine group) would therefore be the only accessible part of this amino acid. It is therefore a good idea to specify if amino acids are substrates or catalytic residues (i.e. part of the enzyme) when asking about biochemical reactions.