Citrulline is a non-proteinogenic amino acid (that is, citrulline is an amino acid that is not coded for in mRNA), and it is an important metabolic intermediate in the Urea Cycle. The Urea Cycle is critical for nitrogen (e.g. ammonia) excretion in humans as well as other mammals.

Citrulline is an interesting amino acid, given its vital function in the Urea Cycle, but also because it has such a high concentration in the watermelon. The name citrulline is actually derived from citrullus vulgaris, which is the Latin word for watermelon.

A notable fact about the watermelon is that the watermelon is the only food known to have such high content of citrulline. There are NO other foods that have such high endogenous levels of this amino acid.

As a physiologist citrulline is very interesting metabolically, but I wonder why the watermelon would have such a high concentration? Why would that occur? Would high citrulline content offer some type of competitive advantage to the watermelon in terms of out-competing other plants? As biologists, we usually think about things from a teleologic perspective in order to make sense of the world around us. With that perspective, is there a logical reason that citrulline would be so enriched in the watermelon? It seems very odd that it would be the only plant with notable quantities.

  • $\begingroup$ I am just a novice undergrad in biology and am a poor student and probably way off base. My chemistry is also really bad. But I read via the wikipedia page that citrulline is a " precursor to producing nitric oxide". I feel like i am using "ad hoc" logic but i also read Nitric Oxide can be responsible for retaining water (ncbi.nlm.nih.gov/pmc/articles/PMC116475) and for disease prevention via cell death (ncbi.nlm.nih.gov/pmc/articles/PMC1810256). Sorry if im way off base, but I always try and make an effort to answer questions, even if I am lost myself. $\endgroup$
    – Ro Siv
    Dec 7, 2015 at 3:58
  • $\begingroup$ @RoSiv, you may not have been that far off, though I think it is likely related to seed development and germination. Google Scholar for Seed Development and Citrulline and Seed Development and Nitric Oxide. I would check Cantaloupe and Cucumbers, things that maintain their seeds in the pulp of the fruit. $\endgroup$
    – AMR
    Dec 7, 2015 at 5:28
  • $\begingroup$ @AMR I like your thinking along with Ro Siv, but unlike watermelon - cantaloupe and cucumbers have very little citrulline... I'm trying to understand why watermelon in particular would have such high concentrations of citrulline compared to all the other known fruits/veggies - seems strange but there must be some type of reason $\endgroup$ Dec 7, 2015 at 16:09
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    $\begingroup$ One of the things I saw was that it was concentrated in the rind. Look to see if watermelon has homologs to PADI4... Maybe it has Multiple gene duplications that are all active... or check its overall arginine distribution in its genome... Maybe its reading frames code for an inordinate amount of arginine when compared to other plants. $\endgroup$
    – AMR
    Dec 7, 2015 at 20:30
  • $\begingroup$ Asking why things happen evolutionary is a bit misleading. One can guess pretty well (for example, skunk cabbage being thermogenic gives it a distinct advantage as it flowers when few other plants can compete for pollinating insects) but the answer, ultimately, is that for some reason, this is how it came to be. May be as simple as an accidental duplication of a particular gene, whatever. But "why" is in this case probably only a guess in an evolutionary perspective. $\endgroup$ Dec 8, 2015 at 18:21

1 Answer 1


According to molecular botanists and plant physiologists, watermelon is the only plant that is known to contain significant amounts of citrulline. Interestingly, it appears that the reason for this tremendous enrichment in citrulline stems from the environment in which wild watermelons naturally thrived hundreds of years ago prior to the development of agriculture.

According to botanists, drought is one of the most severe stresses to which a plant can be exposed. Drought generates a high level of free radicals and oxidative stress, in part because plants maintain their photosynthetic machinery even in the face of severe drought. A number of investigators have shown that different plants have unique molecular mechanisms/systems to allow them to tolerate such harsh conditions and oxidative stress.

Wild watermelon plants inhabit the Kalahari Desert in Botswana, where the annual rainfall is less than 2 cm. Despite the minimal rainfall, the watermelon (a xerophyte) can tolerate the extreme conditions well with an exceedingly high drought tolerance. Surprisingly, this tolerance to intense drought conditions by watermelon plants even persists despite a sub-optimally developed root system. In the case of the watermelon, citrulline is overproduced in the leaves (and apparently the rest of the plant) and citrulline acts as the major hydroxy radical scavenger that allows wild watermelon to tolerate the drought-induced oxidative stress. From this same source (Annals of Botany - link below), there are also other proteins that may also be involved in these mechanisms as well. Even though the citrulline content is predominately used in the leaves to buffer oxidative stress, it appears that it secondarily accumulates in the melon itself.

Note: The image below is from Annals of Botany paper in the links below - it is OPEN ACCESS, which is why I posted the picture and included the reference link. You can clearly see the before and after pictures of drought and how the watermelon leaves appear minimally changed, unlike the radish and cucumber leaves.

See below for some interesting Papers about citrulline, watermelon, and mechanisms of drought-resistance:

Ann Bot. 2002 Jun;89 Spec No:825-32. Citrulline and DRIP-1 protein (ArgE homologue) in drought tolerance of wild watermelon.

FEBS Lett. 2001 Nov 23;508(3):438-42. Citrulline, a novel compatible solute in drought-tolerant wild watermelon leaves, is an efficient hydroxyl radical scavenger.

Citrulline and DRIP-1 Scavengers

  • $\begingroup$ It seems to me that this is a teleological explanation for "why" ("because it suited it's growth in certain regions") as opposed to an objective reason ("because it contains multiple copies of a certain gene for the [etc.] found in plants originating in x region."). I dunno, maybe not. Maybe just me. $\endgroup$ Dec 31, 2015 at 22:19
  • $\begingroup$ @anongoodnurse agreed, teleologic indeed - not my area of expertise but i happened to run across it working on a book chapter (go figure) - I would love someone with a plant background to answer who might have more insight $\endgroup$ Dec 31, 2015 at 22:41
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    $\begingroup$ watermelon.org/Contact Maybe they will be able to give you the contact of a botanist that studies the plant in detail... One interesting fact I didn't know is that the rind is edible as well, and that is where most all of the citrulline is found. $\endgroup$
    – AMR
    Jan 1, 2016 at 0:14
  • $\begingroup$ Also it also appears that the citruilline pathway uses Ornithine instead of Arginine as the human pathway does. But there only appeared to be a single Ornithine cyclodeaminase gene. icugi.org/cgi-bin/ICuGI/genome/search.cgi $\endgroup$
    – AMR
    Jan 1, 2016 at 0:18
  • $\begingroup$ @AMR heard back from watermelon.org... actually send me some scientific studies about the benefits of citrulline, but no idea about why it is enriched in watermelon - FYI $\endgroup$ Feb 15, 2016 at 14:58

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