Carbon Dioxide and the Carbamate Post-Translational Modification

Abstract

Carbon dioxide is essential for life. It is at the beginning of every life process as a substrate of photosynthesis. It is at the end of every life process as the product of post-mortem decay. Therefore, it is not surprising that this gas regulates such diverse processes as cellular chemical reactions, transport, maintenance of the cellular environment, and behaviour. Carbon dioxide is a strategically important research target relevant to crop responses to environmental change, insect vector-borne disease and public health. However, we know little of carbon dioxide’s direct interactions with the cell. The carbamate post-translational modification, mediated by the nucleophilic attack by carbon dioxide on N-terminal α-amino groups or the lysine ɛ-amino groups, is one mechanism by which carbon dioxide might alter protein function to form part of a sensing and signalling mechanism. We detail known protein carbamates, including the history of their discovery. Further, we describe recent studies on new techniques to isolate this problematic post-translational modification.

Interplay of carbon dioxide and peroxide metabolism in mammalian cells

“…On the other hand, HCO4can be reduced by one-electron via transition metal centers to yield CO3 .-. likely HCO4 -+ Me n+ → CO3 .-+ Me (n-1)+ + OH - [29] Thus, the CO2-dependent formation of HCO4leads to the activation of H2O2 for both two-electron [28] and radical [29] chemistry, the latter in combination with transition metals (73,87) Peroxymonocarbonate can be also generated at the active site of redox enzymes and promote CO2-dependent oxidations and peroxidations (87,(95)(96)(97)(98)(99)(100). Two well-known examples of these processes have been described for Cu/Zn-superoxide dismutase (SOD) (96,98,99)and xanthine oxidase (100).…”

“…It is well known that CO 2 can promote modifications in proteins under physiological conditions by its combination with neutral amines to form carbamates ( 27 ). This posttranslational carbamylation reaction involves the nucleophilic attack by CO 2 on N -terminal amino or lysine ɛ-amino groups ( 28 ). It is now also established that CO 2 also participates in oxidative posttranslational modifications reactions mediated by H 2 O 2 and peroxynitrite; these processes require the intermediate formation of CO 2 -derived species such as HCO 4 - and ONOOCO 2 - , respectively, that modulate amino acid oxidation and nitration ( 4 , 8 , 13 ).…”

Hyperpolarized (1-13C)Alaninamide Is a Multifunctional In Vivo Sensor of Aminopeptidase N Activity, pH, and CO2

“…As with pH sensitivity, the ability of hyperpolarized l -(1- 13 C)­alaninamide to sense dissolved CO 2 via reversible carbamate formation was not initially anticipated. However, carbamate formation by proteins, peptides, and amino acids has long been appreciated as a biologically significant reaction, − and compounds bearing primary amines with low p K a s can be expected to readily react with CO 2 . Amine basicity is however likely not the sole factor determining carbamate formation, as this reaction was not observed in vivo with hyperpolarized (1- 13 C)­alanine ethyl ester despite it having a similar p K a of 8 …”

A thermophilic chemolithoautotrophic bacterial consortium suggests a mutual relationship between bacteria in extreme oligotrophic environments

“…(for example, using specific antibiotics and culture conditions, based on the data obtained from the MAGs) may be useful to clarify key mechanism(s) via in-vitro assays; compared with predictions using metagenomic data, such assays are more stable and facilitate the study of biochemical functions with greater accuracy. For example, several apoenzymes involved in carbon and nitrogen metabolism exhibit post-translational modifications and cofactor maturation (such as molybdopterin and Fe-heme) 37 . Isolation of the main component, C. thermoautotrophica StC, would also allow us to examine, model, manipulate, and design metabolic pathways in natural and constructed microbial systems using systemic approaches and synthetic biology.…”