Objective This narrative review examines six important non-nutritive substances in breastmilk, many of which were thought to have little to no biological significance. The overall objective of this narrative review is to provide background on key bioactive factors in breastmilk believed to have an effect on infant outcomes (growth and body composition). Methods The evidence for the effects of the following six bioactive compounds in breastmilk on infant growth outcomes are reviewed: insulin, leptin, adiponectin, ghrelin, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Results The existing literature on the effects of breastmilk insulin, ghrelin, IL-6 and TNF-α and their associations with infant growth and adiposity is sparse. Of the bioactive compounds reviewed, leptin and adiponectin are the most researched. Data reveals that breastmilk adiponectin has negative associations with growth in infancy. Conclusions There is a need for innovative, well-designed studies to improve causal inference and advance our understanding in the effects of breastmilk and its components on offspring growth and body composition. The recommendations provided, along with careful consideration of both known and unknown factors that affect breastmilk composition, will help improve, standardize and ultimately advance this emergent field.

The acetyl coenzyme A synthase (ACS) enzyme plays a central role in the metabolism of anaerobic bacteria and archaea, catalyzing the reversible synthesis of acetyl-CoA from CO and a methyl group through a series of nickel-based organometallic intermediates. Owing to the extreme complexity of the native enzyme systems, the mechanism by which this catalysis occurs remains poorly understood. In this work, we have developed a protein-based model for the Ni center of acetyl coenzyme A synthase using a nickel-substituted azurin protein (NiAz). NiAz is the first model nickel protein system capable of accessing three (Ni/Ni/Ni) distinct oxidation states within a physiological potential range in aqueous solution, a critical feature for achieving organometallic ACS activity, and binds CO and -CH groups with biologically relevant affinity. Characterization of the Ni-CO species through spectroscopic and computational techniques reveals fundamentally similar features between the model NiAz system and the native ACS enzyme, highlighting the potential for related reactivity in this model protein. This work provides insight into the enzymatic process, with implications toward engineering biological catalysts for organometallic processes.

The development of an artificial metalloenzyme for CO2 reduction is described. The small-molecule catalyst [NiII (cyclam)]2+ has been incorporated within azurin. Selectivity for CO generation over H+ reduction is enhanced within the protein environment, while the azurin active site metal impacts the electrochemical overpotential and photocatalytic activity. The enhanced catalysis observed for copper azurin suggests an important role for intramolecular electron transfer, analogous to native CO2 reducing enzymes.

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