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.
Highlights
Amino acids are the fundaments of enzymes, receptors, antibodies, signaling molecules, hormones, and multiple other essential protein structures in all living organisms
We aim to summarize the sources of d-amino acids as well as the processes underlying d-amino acid metabolism in the human body
Since the spontaneous racemization of l-amino acids in these tissues appears to promote the loss of function of their structural proteins, the presence of high d-amino acid levels has been linked to disorders related to aging such as photoaging of the skin, atherosclerosis, macular degeneration, and cataracts [106,111]
Summary
Amino acids are the fundaments of enzymes, receptors, antibodies, signaling molecules, hormones, and multiple other essential protein structures in all living organisms. D-serine (d-Ser) and d-aspartate (d-Asp) are suggested to be the only d-amino acids in the human body originating from tissue intrinsic racemization [31] These d-amino acids are referred to as canonical d-amino acids, and they are the two most commonly studied d-amino acids in relation to human physiology. These (neuro) endocrine effects of d-Asp have predominantly been established in rat studies, whereas human studies are lacking In addition to these canonical d-amino acids, so-called non-canonical d-amino acids (derived via the microbiota or through dietary intake) are currently gaining more and more attention because of their potential involvement in (patho)physiological processes related to, for example, kidney function, innate immunity, and gut barrier regulation, among others [30,40,41]. We will provide an overview of the role of both canonical and non-canonical d-amino acids in health and disease, with a focus on cancer
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