Abstract
Consumption of a high-protein diet increases protein entry into the colon. Colonic microbiota can ferment proteins, which results in the production of protein fermentation end-products, like polyamines. This review describes the effects of polyamines on biochemical, cellular and physiological processes, with a focus on the colon. Polyamines (mainly spermine, spermidine, putrescine and cadaverine) are involved in the regulation of protein translation and gene transcription. In this, the spermidine-derived hypusination modification of EIF5A plays an important role. In addition, polyamines regulate metabolic functions. Through hypusination of EIF5A, polyamines also regulate translation of mitochondrial proteins, thereby increasing their expression. They can also induce mitophagy through various pathways, which helps to remove damaged organelles and improves cell survival. In addition, polyamines increase mitochondrial substrate oxidation by increasing mitochondrial Ca2+-levels. Putrescine can even serve as an energy source for enterocytes in the small intestine. By regulating the formation of the mitochondrial permeability transition pore, polyamines help maintain mitochondrial membrane integrity. However, their catabolism may also reduce metabolic functions by depleting intracellular acetyl-CoA levels, or through production of toxic by-products. Lastly, polyamines support gut physiology, by supporting barrier function, inducing gut maturation and increasing longevity. Polyamines thus play many roles, and their impact is strongly tissue- and dose-dependent. However, whether diet-derived increases in colonic luminal polyamine levels also impact intestinal physiology has not been resolved yet.
Highlights
Intake of protein when consuming a ‘normal’ Western diet contributes to around 15% of total energy intake [1], of which 85%–95% is digested in the small intestine [2]
We focus on the biochemical, cellular and physiological aspects of the role of polyamines in regulating metabolism and proliferation in cells, with a special focus on the effects within the colon
Even though it is known that polyamines play a role in a plethora of cellular functions, much less is known about how luminal polyamines can affect colonic physiology
Summary
Intake of protein when consuming a ‘normal’ Western diet contributes to around 15% of total energy intake [1], of which 85%–95% is digested in the small intestine [2]. By metabolizing the undigested protein, microbiota form and secrete metabolites that impact the host [4] Among these protein-derived metabolites, most are small molecule metabolites, like hydrogen sulfide, branched-chain fatty acids, phenolic compounds and polyamines [4,5]. Increasing protein intake beyond ‘normal’ levels has been shown to be effective for weight-loss management as well as sports performance [6,7]. These benefits of higher protein intake are well documented, it is not completely understood what the physiological effects are of increased concentrations of undigested proteins in the human colon. We focus on the biochemical, cellular and physiological aspects of the role of polyamines in regulating metabolism and proliferation in cells, with a special focus on the effects within the colon
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