d-amino Acids in Health and Disease: A Focus on Cancer

Abstract

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.

Keywords: cancer; food processing; innate immunity; microbiota; racemization.

Figure 1

Overview of protein and mRNA expression profiles of enzymes involved in d-amino acid metabolism in different human tissues. Adapted from the Human Protein Atlas [72] (Version 19, available at https://www.proteinatlas.org).

Figure 2

Schematic overview of d-amino acid sources and (d-amino acid oxidase (DAO)-dependent) links to physiology and disease as discussed in the present review.