1-Aminocyclopropanecarboxylic Acid: Plant Ethylene Precursor and Procognitive Agent

1-aminocyclopropanecarboxylic acid (ACC) is defined as a compound that contains a cyclopropane ring, with an amino group and a carboxylic acid functional group attached, which can be substituted to form various derivatives. 1-Aminocyclopropanecarboxylic acid (ACC) has been used as a substrate for determining ACC deaminase activity to study the plant growth-promoting characteristics of endophytic isolates obtained from Pteris vittata roots, cucurbit seeds. It has also been used as an ethylene precursor to study the effect of high ethylene concentration on lateral root density (LRD) in sorghum brown midrib (bmr) mutants.

1-Aminocyclopropanecarboxylic acid produces procognitive effects in rats

1-Aminocyclopropanecarboxylic acid (ACPC) is a high-affinity partial agonist at the strychnine-insensitive glycine sites that exhibits anticonvulsant, neuroprotective, anxiolytic, anti-addictive and antidepressant-like effects in rats and mice. This broad range of pharmacological effects is reminiscent of NMDA antagonists. However, in contrast to NMDA receptor antagonists acting at other loci and the full antagonist of the glycine site 7-chloro-kynurenic acid that impair spatial learning, the functional NMDA/glycine receptor antagonist ACPC does not impair memory or learning processes in a step-through avoidance. Conversely, preclinical studies demonstrated that 1-Aminocyclopropanecarboxylic acid facilitates spatial learning in senescent rats and in mice tested in a single-trial inhibitory avoidance learning both in naive animals and following administration of a variety of amnestic agents. These properties make ACPC a particularly interesting molecule to investigate both in tests addressing cognitive deficits observed in schizophrenia (NMDAR antagonist-disturbed conditions, prefrontal cognitive flexibility) as well as in procedures used to detect potential antipsychotic activity. Here, 1-Aminocyclopropanecarboxylic acid was also tested in the five-choice serial reaction time task, a procedure that permits the simultaneous examination of multiple aspects of attentional performance including the accuracy of attentional processes and impulsivity. While NMDAR antagonists have been demonstrated to disrupt attentional performance and/or increase impulsivity, the effects of glycinergic compounds have not been widely assessed in this task.[1]

The present study demonstrates that 1-Aminocyclopropanecarboxylic acid, a partial agonist at the strychnine-insensitive glycine receptors facilitates object recognition learning in the novel object recognition test in both the presence and absence of NMDAR antagonists, and enhances cognitive flexibility in the attentional set-shifting task. However, ACPC produced no measurable effects in PCP-induced hyperactivity, conditioned avoidance response, and prepulse inhibition tests, suggesting a lack of antipsychotic-like activity. Like MK-801, ACPC did not affect accuracy in the five-choice serial reaction time task, but in contrast to very low doses of MK-801, no increase in impulsivity was observed. The latter findings strongly suggest prominent differences in the pharmacological profile of 1-Aminocyclopropanecarboxylic acid compared to NMDA channel blockers. Thus, despite the functional antagonist properties of ACPC documented in multiple studies, it did not disturb object recognition learning like PCP and ketamine, did not disturb prepulse response like ketamine, and did not affect impulsivity like MK-801. These clinical observations reveal the potential for glycine site partial agonists to mimic the pharmacological actions of both glycine site agonists and antagonists, which is consistent with the present demonstration that 1-Aminocyclopropanecarboxylic acid possesses procognitive, but not antipsychotic-like efficacy.

Accumulation and Transport of 1-Aminocyclopropane-1-Carboxylic Acid

1-Aminocyclopropanecarboxylic acid (ACC) is a three-membered ring non-protein amino acid which is the direct precursor of the plant hormone ethylene. This gaseous plant hormone was identified as a regulator of plant growth in 1901 by Neljubov. Decades of dedicated research revealed a myriad of plant responses to ethylene. This two-carbon atom molecule controls several processes linked to vegetative plant growth but is also a major player in seed germination, fruit ripening, leaf and flower senescence and abscission. The majority of the regulatory mechanisms of ethylene biosynthesis act at the level of ACC production by ACS. However, there are additional regulatory mechanisms. Under conditions of high ethylene production, the pathway can also be regulated at the level of the conversion of ACC into ethylene by ACO. Conjugation and deamination of ACC regulates the pool of available 1-Aminocyclopropanecarboxylic acid. In addition, the ACC pool is also indirectly altered by action of VAS1. For many hormones, the site of synthesis does not always coincide with the site of action. The same has been observed for ethylene. Because ethylene is a gaseous molecule, it diffuses rapidly through the plant tissues inducing mainly local responses, with the exception of aerenchyma through which long distance transport can be conducted, as observed in conditions of waterlogging.[2]

The secretion of 1-Aminocyclopropanecarboxylic acid into the rhizosphere to attract and interact with PGPR, as discussed in the previous section, is an example of an ethylene-independent function for ACC. Recent studies present evidence that ACC, or one of its derivates, might also have other signaling roles independent from ethylene. Aiming at a more profound understanding of ACC transport, it is tempting to look at the organ and cell-type specific gene expression patterns of the ethylene biosynthesis genes ACS and ACO as a main determinant of ACC accumulation. In tissues with high ACS expression, where, however, little or no ACO expression is found, 1-Aminocyclopropanecarboxylic acid export might be important. In contrast, in tissues with low ACS expression, though high ACO expression, ACC import might be important. For an overview of the detailed expression patterns for both enzyme families, we extracted cell-type specific and developmental stage specific absolute expression values from the Toronto Arabidopsis eFP browser (BAR). First, a better understanding of the transcriptional or post-translational control of ACO is necessary. Foremost, a profound understanding of 1-Aminocyclopropanecarboxylic acid transport, including identification of genes encoding different types of transporters, together with a detailed organ-specific metabolomics study of ACC and its conjugates, would help to draw a map of ACC traffic within the plant body.

1-Aminocyclopropanecarboxylic acid in plants

The major discovery that made the methionine cycle in plants unique from all other organisms, was the characterization of 1-Aminocyclopropanecarboxylic acid(ACC) as the intermediate between SAM and ethylene were able to identify ACC as the precursor for ethylene by feeding experiments on apple tissue, using radio-labeled methionine. Upon incubation of apple disks, they observed a shift from ethylene production in air, toward an unknown compound that was retained in the tissue when treated with nitrogen (lack of oxygen inhibits oxidation of ACC toward ethylene). By using a pH-dependent ion mobility assay, they could characterize this unknown component as an amino acid. Subsequently, the component was identified as ACC, using co-migration of synthetic 1-Aminocyclopropanecarboxylic acid for both paper-chromatography and paper-electrophoresis.[3]

Ethylene is a simple two carbon atom molecule with profound effects on plants. There are quite a few review papers covering all aspects of ethylene biology in plants, including its biosynthesis, signaling and physiology. This is merely a logical consequence of the fascinating and pleiotropic nature of this gaseous plant hormone. Its biochemical precursor, 1-Aminocyclopropanecarboxylic acid is also a fairly simple molecule, but perhaps its role in plant biology is seriously underestimated. This triangularly shaped amino acid has many more features than just being the precursor of the lead-role player ethylene. For example, ACC can be conjugated to three different derivatives, but their biological role remains vague. ACC can also be metabolized by bacteria using ACC-deaminase, favoring plant growth and lowering stress susceptibility. 1-Aminocyclopropanecarboxylic acid is also subjected to a sophisticated transport mechanism to ensure local and long-distance ethylene responses. Last but not least, there are now a few exciting studies where ACC has been reported to function as a signal itself, independently from ethylene.

References

[1]Popik P, Holuj M, Nikiforuk A, Kos T, Trullas R, Skolnick P. 1-aminocyclopropanecarboxylic acid (ACPC) produces procognitive but not antipsychotic-like effects in rats. Psychopharmacology (Berl). 2015 Mar;232(6):1025-38. doi: 10.1007/s00213-014-3738-4. Epub 2014 Sep 27. PMID: 25260339; PMCID: PMC4336651.

[2]Vanderstraeten L, Van Der Straeten D. Accumulation and Transport of 1-Aminocyclopropane-1-Carboxylic Acid (ACC) in Plants: Current Status, Considerations for Future Research and Agronomic Applications. Front Plant Sci. 2017 Jan 24;8:38. doi: 10.3389/fpls.2017.00038. PMID: 28174583; PMCID: PMC5258695.

[3]Van de Poel B, Van Der Straeten D. 1-aminocyclopropane-1-carboxylic acid (ACC) in plants: more than just the precursor of ethylene! Front Plant Sci. 2014 Nov 11;5:640. doi: 10.3389/fpls.2014.00640. PMID: 25426135; PMCID: PMC4227472.

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