Biosynthesis and Metabolic Pathways of Coenzymes

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 7585

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Department of Pharmacology, University of South Alabama, 5851 USA Drive North, MSB 3370, Mobile, AL 36688, USA
Interests: organic synthesis; nucleoside, nucleotides, dinucleotides, phosphate chemistry; ionic liquids in organic chemistry; mechanochemistry; isotopic and fluorescent tracing; metabolomics; nanoparticle generation and characterization; cell metabolism; mitochondrial dysfunction; metabolic and signaling coenzymes (NAD; FAD; SAM; Acyl-CoA)-biosynthetic pathways in cancer
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Special Issue Information

Dear Colleagues,

In a cell, homeostasis is maintained when the cell has the capacity, and sustained ability, to compensate for biochemical events that are challenged by a lack or excess of biosynthetic precursors or enzymatic products. Many of these biochemical events rely on the sustained abundance of simple precursors and the enzymes responsible for their conversion.  In many cases, these conversions also require the contribution of coenzymes (e.g., ThPP, FAD, NAD, CoA, PLP, biotin, folate, cobalamin, SAM, and coQ) in addition to cofactors such as metals and ATP. These coenzymes and cofactors are not only central to metabolism, but many are also directly involved in the orchestration of a plethora of protein-driven signaling events that consume them (e.g., NAD+ (protein ADP-ribosylation and deacylation), acyl-coA (protein acylation), and SAM (nucleic acid and histone methylation)). Since these mediators are consumed, they can be readily depleted upon cellular response to intra and extracellular signaling events and their abundance can vary greatly over a cell cycle with physiological consequences that are slowly becoming better understood, such as loss of homeostasis.

The biosynthetic pathways that cells have available to maintain coenzymes levels can vary greatly across the phyla, organism and cell type. In mammals, most coenzymes are derived from vitamins but what constitutes a vitamin for some organisms is endogenously produced by others and this symbiosis is slowly emerging as being central to human health. Overall, these coenzymes are prone to regulation, via the abundance of their respective precursors as well as by genetic and epigenetic regulation. Crucially, these biosynthetic pathways often rely on the abundance of multiple coenzymes. For example, the interconversion of folate-derived coenzymes requires FAD and NADPH, while NAD de novo biosynthesis from tryptophan requires PLP and ThPP. As such, the interdependence of coenzyme biosynthesis should not be underestimated, as the reduction in one coenzyme form can affect the generation of another coenzyme whose abundance affects widely different cellular processes. Recently, the bioavailability of coenzymes and regulation of their biosynthetic pathways have become targets of drug development, either with the view to boosting their abundance for the improvement of cellular function or to inhibit their formation to promote cell death.  We seek manuscript submissions for a special edition to highlight the interconnectivity and interdependence of coenzymes and their metabolic pathways in the maintenance of cellular homeostasis.

Prof. Dr. Marie Migaud
Guest Editor

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Keywords

  • coenzymes
  • cofactor
  • homeostasis
  • Acyl-CoA (ThDP, FAD……)
  • FMN
  • folate
  • biotin
  • metals/ATP
  • metabolic pathways

Published Papers (2 papers)

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Research

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13 pages, 4910 KiB  
Article
Early Evolutionary Selection of NAD Biosynthesis Pathway in Bacteria
by Suraj Sharma, Yin-Chen Hsieh, Jörn Dietze, Mathias Bockwoldt, Øyvind Strømland, Mathias Ziegler and Ines Heiland
Metabolites 2022, 12(7), 569; https://doi.org/10.3390/metabo12070569 - 21 Jun 2022
Cited by 3 | Viewed by 1978
Abstract
Bacteria use two alternative pathways to synthesize nicotinamide adenine dinucleotide (NAD) from nicotinamide (Nam). A short, two-step route proceeds through nicotinamide mononucleotide (NMN) formation, whereas the other pathway, a four-step route, includes the deamidation of Nam and the reamidation of nicotinic acid adenine [...] Read more.
Bacteria use two alternative pathways to synthesize nicotinamide adenine dinucleotide (NAD) from nicotinamide (Nam). A short, two-step route proceeds through nicotinamide mononucleotide (NMN) formation, whereas the other pathway, a four-step route, includes the deamidation of Nam and the reamidation of nicotinic acid adenine dinucleotide (NAAD) to NAD. In addition to having twice as many enzymatic steps, the four-step route appears energetically unfavourable, because the amidation of NAAD includes the cleavage of ATP to AMP. Therefore, it is surprising that this pathway is prevalent not only in bacteria but also in yeast and plants. Here, we demonstrate that the considerably higher chemical stability of the deamidated intermediates, compared with their amidated counterparts, might compensate for the additional energy expenditure, at least at elevated temperatures. Moreover, comprehensive bioinformatics analyses of the available >6000 bacterial genomes indicate that an early selection of one or the other pathway occurred. The mathematical modelling of the NAD pathway dynamics supports this hypothesis, as there appear to be no advantages in having both pathways. Full article
(This article belongs to the Special Issue Biosynthesis and Metabolic Pathways of Coenzymes)
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Review

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18 pages, 1416 KiB  
Review
NAD+ Precursors: A Questionable Redundancy
by Carles Canto
Metabolites 2022, 12(7), 630; https://doi.org/10.3390/metabo12070630 - 9 Jul 2022
Cited by 9 | Viewed by 4788
Abstract
The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD+ bioavailability. Among them, the dietary supplementation with NAD+ precursors—classically known as vitamin B3—has received most of the [...] Read more.
The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD+ bioavailability. Among them, the dietary supplementation with NAD+ precursors—classically known as vitamin B3—has received most of the attention. Multiple molecules can act as NAD+ precursors through independent biosynthetic routes. Interestingly, eukaryote organisms have conserved a remarkable ability to utilize all of these different molecules, even if some of them are scarcely found in nature. Here, we discuss the possibility that the conservation of all of these biosynthetic pathways through evolution occurred because the different NAD+ precursors might serve specialized purposes. Full article
(This article belongs to the Special Issue Biosynthesis and Metabolic Pathways of Coenzymes)
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