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I would like to start by clarifying that I do not claim that the extant pathways of the Stickland reaction are directly derived from the putative ancient pathways for amino acid fermentation, as discussed in the main text.
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The following section will focus on the molecular mechanisms that guided this transition, i.e., the expansion and the refinement of ancestral metabolic routes, leading to the structure of the extant metabolic pathways.
On the other hand, the analysis of the mechanism of reaction of simple organic molecules reveals instances in which key intermediates are also produced corresponding to those observed in extant biological pathways.
The enormous number of protein primary structure data resulting from genomic sequencing efforts of the past 25 years provide compelling evidence that enzyme recruitment is pervasive in extant metabolic pathways.
The expression levels of extant senescence pathways are likely to be altered by the processes of transformation and tumour progression and may reflect the route to immortalisation in individual tumour types.
Gene fusion is considered to be an important evolutionary path to create novelty in protein architectures (the linear arrangement of protein domains) and functions by forming composite proteins and linking components of extant signaling/biochemical pathways [ 16].
Therefore, tumours must retain extant senescence pathways, though it is unclear how their expression is changed during the process of transformation in different cells and whether these expression levels might relate to the propensity to undergo cell cycle arrest in response to appropriate therapeutic intervention.
This hardly places the extant Stickland reaction pathways in a deep ancestral branch of the tree of life, but it is conceivable that analogous, if not ancestral, versions of Stickland reaction pathways not only existed before the code was established, but could also have played a role in the establishment of the code, before the catalytic role was implemented and translation evolved.
Hence it is conceivable that an ancient class I CO pathway did not completely disappear and that functions of it have been integrated with the extant (class II?) pathway in Tetrahymena.
But the existence of these pathways in extant organisms make amino acid fermentation plausible.
This study confirms the complexity and mosaic nature of the central carbohydrate metabolic pathways in extant organisms.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com