When should a psychiatrist remember to test homocysteine levels? - a literature review

Introduction: Homocysteine is an endogenous sulfur amino acid, formed as a result of biochemical changes in methionine. The normal concentration of homocysteine in healthy people is within the range of 5 – 15 μmol / l, and values above 15 μmol / l are referred to as hyperhomocysteinemia. Moreover, it has been shown that the level of homocysteine may be associated with the occurrence of mental disorders. The aim of this article was to search for a relationship between the level of this amino acid and the incidence and prognosis of bipolar disorder, depression, anxiety disorders, schizophrenia or Alzheimer's disease. Material and method: For the review of the literature, available articles from the PubMed database and Google Scholar were used under the following keywords: homocysteine, depression, bipolar disorder, schizophrenia, Alzheimer's disease in the period from 1992 to 2021. Results: The research conducted so far shows that there is a significant correlation between elevated levels of homocysteine and the above-mentioned mental disorders. Conclusion: In order to prevent the consequences of the increased level of homocysteine, its concentration in blood serum should be monitored periodically and appropriate treatment should be implemented in case of abnormal results. It is important to educate patients about the consequences of hyperhomocysteinemia i.a. atherosclerosis, stroke, ischemic heart disease, osteoporosis, neural tube defects, mental disorders and neurodegenerative diseases. It should be also established a strategy to lower the level of this amino acid through lifestyle changes, as well as the supply of folic acid, vitamins B12, B6, B2, N-acetylcysteine and betaine.

Hydrogen sulfide, microbiota, and sulfur amino acid restriction diet

Eukaryotes and microbiota produce H2S, using the same substrates and enzymes which constitute the reverse-trans-sulfuration and transsulfuration pathways. The homeostasis of gut microbiota impacts on the structural and functional integrity of gut epithelial barrier. Microbiota also serve as signalling sources to inform the host of the metabolism and functional changes. Microbiota dysbiosis negatively affect human health, contributing to diseases like obesity, diabetes, inflammatory bowel diseases, and asthma. Not by coincidence, these pathological conditions are also closely related to the abnormal metabolism and function of H2S signalling.H2S serves as a bacterial signal to the host and the host-produced H2S impacts on the population and size of microbiota. These bi-directional interactions become especially important for the digestion and utilization of sulfur amino acid in diet. Dietary restriction of sulfur amino acid increases the endogenous production of H2S by the host and consequently offers many health benefits. It, on the other hand, decreases the nutritional supply to the microbiota, which could be remedied by the co-application of prebiotics and probiotics. It is strategically sound to target the expression of H2S-producing enzymes in different organs to slow aging processes in our body and promote better health.

Combining Genome-Wide Gene Expression Analysis (RNA-seq) and a Gene Editing Platform (CRISPR-Cas9) to Uncover the Selectively Pro-oxidant Activity of Aurone Compounds Against Candida albicans

Candida albicans is the major fungal cause of healthcare-associated bloodstream infections worldwide with a 40% mortality rate. The scarcity of antifungal treatments due to the eukaryotic origin of fungal cells has challenged the development of selectively antifungal drugs. In an attempt to identify novel antifungal agents, aurones SH1009 and SH9051, as synthetically bioactive compounds, have been recently documented as anti-Candida agents. Since the molecular mechanisms behind the inhibitory activities of these aurones in C. albicans are unclear, this study aimed to determine the comprehensive cellular processes affected by these aurones and their molecular targets. Genome-wide transcriptional analysis of SH1009- and SH9051-treated C. albicans revealed uniquely repressed expression in different metabolic pathways, particularly trehalose and sulfur amino acid metabolic processes for SH1009 and SH9051, respectively. In contrast, the most commonly enriched process for both aurones was the up-regulation of RNA processing and ribosomal cleavages as an indicator of high oxidative stress, suggesting that a common aspect in the chemical structure of both aurones led to pro-oxidative properties. Additionally, uniquely induced responses (iron ion homeostasis for SH1009 and arginine biosynthesis for SH9051) garnered attention on key roles for the aurone functional groups. Deletion of the transcription factor for the trehalose biosynthesis pathway, Tye7p, resulted in an SH1009-resistant mutant, which also exhibited low trehalose content, validating the primary molecular target of SH1009. Aurone SH9051 uniquely simulated an exogenous supply of methionine or cysteine, leading to sulfur amino acid catabolism as evidenced by quantifying an overproduction of sulfite. Phenyl aurone, the common structure of aurones, contributed proportionally in the pro-oxidative activity through ferric ion reduction effects leading to high ROS levels. Our results determined selective and novel molecular mechanisms for aurone SH1009 and also elucidated the diverse cellular effects of different aurones based on functional groups.

Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements

Background Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health. Method/design Men and women (calculated sample size = 60), aged 18–45 years, with body mass index of 27–35 kg/m2 will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAAhigh, total diet SAA ~ 50–60 mg/kg body weight/day; SAAlow, total diet SAA ~ 15–25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation. Discussion The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders. Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021