New Insights into the Roles of Cysteine and Homocysteine in Pathological Processes

Abstract

Both cysteine and homocysteine are sulfur-containing amino acids with distinct roles in cellular processes. This chapter explores novel perspectives on the roles of cysteine and homocysteine in pathological processes, delving into their intricate involvement in various disease pathways. Additionally, the chapter elucidates the regulatory mechanisms governing homocysteine metabolism and its implications for a range of pathological conditions, including cardiovascular diseases and neurodegenerative disorders. By synthesizing recent research findings, this chapter aims to provide fresh insights into the nuanced interplay among cysteine, homocysteine, and disease progression. The exploration of these sulfur-containing amino acids opens avenues for understanding pathophysiological mechanisms and suggests potential targets for therapeutic interventions.

1. Introduction

Cysteine, an amino acid of particular importance in cell biology, serves as an essential component in the construction of the fundamental building blocks of life—proteins. With a distinctive chemical structure, characterized by the presence of the thiol group (‒SH) in its side chain, cysteine holds crucial roles in stabilizing protein structure and maintaining oxidative balance in the body’s cells [1, 2]. Although, usually, the body can synthesize cysteine, there are circumstances in which its necessity becomes conditionally essential, justifying the importance of adequate intake through food or, in certain cases, supplementation. The various aspects of cysteine, from its contribution to the formation of disulfide bonds into proteins to its antioxidative capacity and involvement in cellular detoxification processes, provide clear insight into the importance of cysteine in maintaining cellular health and essential physiological functions [3].

Homocysteine, an organic compound derived from the essential amino acid methionine, has become the subject of considerable interest in the scientific and medical field due to its link to various conditions and diseases. Normally, methionine, an amino acid obtained from food, is metabolized in the body to produce homocysteine, and its levels are strictly regulated [4, 5]. However, when this balance is disrupted, homocysteine can reach high levels, associated with an increased risk for cardiovascular disease, neurological disease, and others (Figure 1) [6].

Figure 1.

Homocysteine associated diseases.

Homocysteine metabolism is closely related to adequate intake of B vitamins, especially B6, B9 (folic acid), and B12. Deficiencies in these vitamins can lead to the accumulation of homocysteine in the blood. Genetic factors can also influence homocysteine levels [7]. Studies have shown that an increased level of homocysteine in the blood may be an independent risk factor for cardiovascular disease, as it can contribute to damage to the vascular wall and promote blood clots [8, 9]. It has also been suggested that homocysteine may play a role in inflammatory and degenerative processes in the nervous system, contributing to neurodegenerative diseases, such as Alzheimer’s disease or Parkinson’s disease [10, 11]. Monitoring homocysteine levels and adopting a healthy lifestyle that includes a balanced diet and appropriate B vitamin supplements can help keep these levels within normal limits and reduce the risk associated with elevated homocysteine levels [12].

In this presentation, we explore the nature and roles of cysteine and homocysteine in the body, analyzing their implications for health and their connections to various pathologies. Understanding these molecules provides a significant perspective on how nutritional and genetic factors can influence cardiovascular health and neurological functions, prompting research and interventions for the prevention and management of complications associated with elevated levels of homocysteine.

2. Cysteine and homocysteine metabolism

Cysteine and homocysteine are amino acids involved in important metabolic pathways within the body. Here’s an overview of their metabolism.

Homocysteine, a sulfur-containing amino acid, is produced in the metabolic process of methionine, an essential amino acid present in animal-derived proteins [13]. This compound follows two primary metabolic pathways: remethylation, leading to the regeneration of methionine, and transsulfuration, resulting in its conversion to cysteine. Methionine serves as the primary supplier of methyl radicals in the body, delivered in the form of S-adenosylmethionine (SAM), which is subsequently transformed into S-adenosylhomocysteine (SAH). Homocysteine is produced through the breakdown of SAH, a process catalyzed by S-adenosylhomocysteine hydrolase (SAHH; EC 3.3.1.1). Enzymatic processes play a crucial role in the metabolism of homocysteine, a sulfur-containing amino acid. These processes involve various enzymes, such as methionine synthase (MS; EC 2.1.1.13) and N5,10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20), which catalyze important reactions in the conversion of homocysteine to methionine. Additionally, the activity of these enzymes is dependent on cofactors such as cobalamin and N5-methyltetrahydrofolate. The genetic association between the genes encoding methionine synthase and N5,10-methylenetetrahydrofolate reductase suggests a close relationship between these enzymes and the tetrahydrofolate metabolism (Figure 2) [14, 15, 16, 17].

Figure 2.

Homocysteine metabolism. Methionine adenosyltransferase (MAT); methyltransferase (MT); S-adenosylhomocysteine hydrolase (SAHH); betaine-homocysteine S-methyl transferase (BHMT); cystathionine β-synthase (CBS); cystathionine γ-lyase (CSE); methionine synthase (MS). Adapted from Filip et al. [14].

The remethylation of homocysteine is an important biochemical process that plays a crucial role in maintaining optimal health and functioning in the body. There are multiple pathways involved in the remethylation of homocysteine, including the betaine pathway and the methionine synthase pathway. The betaine pathway utilizes betaine, derived from choline, and is facilitated by the enzyme betaine-homocysteine S-methyltransferase (BHMT; EC 2.1.1.5) [14, 18, 19]. This pathway is primarily active in the liver and kidneys. The methionine synthase pathway, on the other hand, is present in all tissues of the body. One-carbon metabolism is a network of interrelated biochemical reactions that includes the remethylation of homocysteine. One-carbon metabolism is essential for DNA methylation and synthesis, with methionine serving as the main methyl group donor. Not only does the remethylation of homocysteine contribute to methyl group synthesis, but it also serves as a means to prevent the intracellular accumulation of S-adenosylhomocysteine and an increase in plasma total homocysteine levels [14, 20, 21, 22]. Accumulation of elevated levels of homocysteine and adenosine at the cellular level has been demonstrated to completely inhibit all methylation reactions [23, 24, 25]. The conversion of homocysteine to cysteine occurs through cystathionine.

Cystathionine β-synthase (CBS; EC 4.2.1.22) and cystathionine γ-lyase (CSE; EC 4.4.1.1) are enzymes involved in the synthesis of cysteine (Figure 2). Cystathionine β-synthase and cystathionine γ-lyase play crucial roles in the metabolism of cysteine, a non-essential amino acid that is important for various physiological processes in the body. These enzymes facilitate the conversion of homocysteine and serine into cystathionine, which is then further processed to produce cysteine and other essential molecules. The synthesis of cysteine relies on the activity of cystathionine β-synthase and cystathionine γ-lyase enzymes. These enzymes work together to catalyze the reactions necessary for cysteine synthesis. They both require pyridoxal-5-phosphate, the active form of vitamin B6, as a cofactor for their enzymatic activity [26, 27, 28]. Moreover, alterations in the activity or concentration of cystathionine β-synthase and cystathionine γ-lyase have been associated with various pathological conditions and diseases, including diabetes, cancer, AIDS, neurodegenerative disorders, and liver diseases [29, 30, 31]. Furthermore, the enzymes cystathionine β-synthase and cystathionine γ-lyase are also involved in maintaining glutathione metabolism and transport [31, 32]. These enzymes contribute to cellular reactions, such as antioxidant defense, drug detoxification, and cell signaling [33].

Activation of the transsulfuration pathway can promote the production of H₂S [34]. Certainly, cysteine metabolism is intricately linked to methionine metabolism. The process of synthesizing cysteine from methionine comprises four sequential steps. The first two stages are integrated into the methionine cycle, while the subsequent two phases are integral components of the transsulfuration pathway. This interconnected series of events underscores the dynamic relationship between cysteine and methionine within cellular metabolism. The process commences with methionine, leading to the formation of S-adenosylmethionine. Subsequently, SAM contributes to the synthesis of homocysteine. In the initial step of the transsulfuration pathway, cystathionine-β-synthase enzymatically couples homocysteine with serine, resulting in the generation of cystathionine. Subsequent to this, in the subsequent reaction, cystathionine undergoes cleavage catalyzed by cystathionin-γ-lyase, yielding cysteine. This sequence of reactions elucidates the transformation of methionine into cysteine through the transsulfuration pathway [35]. To finalize the synthesis of the GSH tripeptide from cysteine, two additional reactions are essential (Figure 3).

Figure 3.

Scheme of glutathione (GSH) biosynthesis. Adapted from Potega et al. [36]. GS = glutathione synthetase; γ-GCS = γ-glutamylcysteine synthetase.

Initially, the enzyme γ-glutamyl cysteine synthetase (γ-GCS) facilitates the combination of cysteine with glutamate, leading to the creation of γ-glutamylcysteine. Subsequently, in the second reaction catalyzed by the enzyme glutathione synthetase (GS), GSH is produced from γ-glutamylcysteine and glycine [36]. GSH, also known as glutathione, possesses the ability to undergo oxidation, thereby contributing to the maintenance of redox homeostasis. In a reducing environment, such as in the presence of reactive oxygen species (ROS), a disulfide bridge forms between two GSH molecules [37]. This linkage results in the formation of glutathione disulfide (GSSG). The capacity of GSH to undergo redox transformations is crucial for its involvement in cellular antioxidant defense mechanisms. Cysteine synthesis and homocysteine metabolism intersect in the transsulfuration pathway. This pathway can influence the balance between cysteine and homocysteine levels.

3. Cysteine, homocysteine, and mitochondrial dysfunction

The interplay among cysteine, homocysteine, and mitochondrial dysfunction is intricate, involving diverse biochemical processes. Cysteine and homocysteine, being sulfur-containing amino acids, possess the potential to impact mitochondrial function through various metabolic pathways. The complexity of this relationship stems from the multifaceted influence these amino acids exert on mitochondrial processes [38].

Hyperhomocysteinemia induces DNA fragmentation via poly (ADP-ribose) polymerase cleavage, an enzymatic activity effectively suppressed by melatonin. The impact of homocysteine on the function of thioretinaco ozonide within mitochondria and endoplasmic reticulum leads to excitotoxicity, oxidative stress, endothelial dysfunction, and inflammation [39]. Melatonin reduces oxidative damage in the mitochondria of cultured mouse liver cells by diminishing oxygen consumption, lowering membrane potential, and decreasing superoxide production. Matrix metalloproteinase-9 activation in hyperhomocysteinemic rats is triggered by the opening of the mitochondrial permeability transition pore and antagonism of the N-methyl-D-aspartate receptor-1 (NMDA-R1), resulting in myocyte dysfunction due to elevated calcium overload and oxidative stress [40]. The homocysteine-inducible, endoplasmic reticulum (ER) stress-inducible, ubiquitin-like domain member 2 (HERPUD1) in cultured HELA cells facilitate cytoprotective effects against oxidative stress by suppressing the inositol 1,4,5-triphosphate receptor and reducing the transfer of calcium ions from the endoplasmic reticulum to mitochondria [41]. Homocysteine serves as a precursor to hydrogen sulfide (H₂S), a gasotransmitter generated through the transsulfuration process catalyzed by the enzyme’s cystathionine β-synthase and cystathionine γ-lyase. Recently recognized as a novel mediator in cardiovascular homeostasis, H₂S functions as a potent vasodilator with diverse roles [42]. H₂S is primarily generated from L-cysteine, obtained through dietary intake, extraction from endogenous proteins, or endogenous synthesis via the transsulfuration of serine by L-methionine, a process occurring within the transsulfuration pathway. Significantly, L-cysteine serves as a crucial precursor for the biosynthesis of glutathione (GSH), and its initiation into this pathway is a limiting factor [43]. Consequently, mechanisms that modulate the availability of L-cysteine are likely to impact both the H₂S production pathway and GSH biosynthesis, as evidenced by metabolomics and transcriptomics studies conducted in diverse models of mitochondrial dysfunction. As an illustration, investigations into the impact of 1-methyl-4-phenylpyridinium (MPP+), known for its neurotoxic effects mediated by various mechanisms, including complex I (CI) inhibition, demonstrated elevated glutathione (GSH) levels coupled with the upregulation of ATF-4 and the transsulfuration enzymes CTH and CBS. In cellular stress induced by MPP+, the knockdown of ATF-4 or CTH resulted in a reduction of GSH levels [43, 44].

4. The roles of cysteine and homocysteine in pathological processes

4.1 Cysteine and homocysteine in cardiovascular disease

Cardiovascular disease (CVD) stands as the leading cause of global mortality, impacting both developed and developing nations. Numerous studies have explored the relationship between elevated homocysteine (Hcy) levels and the onset of various vascular conditions [45]. Some researchers argue that maintaining a plasma Hcy concentration below 10 μmol/L is essential to mitigate the heightened risk of CVD and ischemic heart disease [46]. A meta-analysis has revealed a positive correlation, indicating that a 25% increase in plasma Hcy levels corresponds to a 10% higher risk of CVD and a 20% higher risk of stroke. Furthermore, another meta-analysis highlighted a 16% reduction in coronary heart disease when serum Hcy levels decreased by 3 μmol/L. Additionally, a 5 μmol/L elevation in plasma Hcy was associated with a 1.6–1.8 times increased relative risk of coronary heart disease [47]. Further investigations have underscored the significant impact of homocysteine on mortality and heart disease [48]. Hcy is implicated in cardiovascular disease through diverse mechanisms, including the heightened proliferation of muscle cells leading to vessel constriction, modification of blood coagulation properties, oxidative damage to the vascular endothelium, and harm to arterial walls [49].

Moreover, Hcy has demonstrated a positive correlation with both diastolic and systolic blood pressures. For example, a 5 μmol/L elevation in Hcy concentration has been correlated with a 0.5 mmHg rise in diastolic blood pressure and a 0.7 mmHg increase in systolic blood pressure. In the case of women, the relationship between Hcy and blood pressure was more pronounced, resulting in a 0.7 mmHg increase in diastolic blood pressure and a 1.2 mmHg increase in systolic blood pressure [50, 51, 52].

Epidemiological research has uncovered a U-shaped correlation between cardiovascular diseases and total cysteine (tCys) after adjusting for other risk factors and homocysteine [52]. Van den Brandhof and colleagues [53], in their study, did not observe a significant association between tCys and the risk of coronary heart disease. Similarly, a study within the Hordaland Homocysteine Study cohort explored the link between tCys and the risk of mortality and cardiovascular disease. The findings of this study concluded that tCys was not connected to all-cause cardiovascular disease or non-cardiovascular disease mortality [54].

Subsequent research endeavored to evaluate the association between total homocysteine (tHcy) and cardiovascular disease, along with mortality and morbidity unrelated to CVD. The findings suggested that tHcy functions as a biomarker for both CVD and non-CVD-related mortality and morbidity [33, 54, 55].

4.2 Cysteine and homocysteine in kidney diseases

As evidenced by several studies, the kidneys play a pivotal role in the regulation of the methionine cycle, exerting a direct influence on alterations in the concentrations of homocysteine, cysteine, S-adenosylmethionine, S-adenosylhomocysteine, and the SAH/SAM ratio [56, 57].

Despite not fully comprehending the mechanisms underlying these disorders in chronic kidney disease (CKD), the robust association among homocysteine, cysteine, S-adenosylmethionine, S-adenosylhomocysteine, and plasma creatinine levels, as well as the glomerular filtration rate (GFR), indicated that these compounds were excreted in the urine. The presence of enzymes in the trans-sulfonation and remethylation pathways in human kidney tissue implies the potential involvement of renal metabolism in these processes [58].

Alterations in the concentrations of Cys and Hcy in blood plasma serve as early indicators, implying that there is initially a primary disruption in the aminothiol metabolism. This disturbance persists until a more pronounced decrease in glomerular filtration rate occurs, along with a disruption in the elimination of these compounds [58].

Krugovla et al. [59] reported that individuals at stages III–V of chronic kidney disease exhibit significantly reduced urine levels of S-adenosylmethionine and SAM/S-adenosylhomocysteine ratio, as well as a decreased cysteine/homocysteine ratio in blood plasma in comparison to patients at stage II of CKD. Notably, the levels of urine SAM serve as a discriminative factor, enabling the differentiation between patients with mildly decreased kidney function and those with moderate to severe renal impairment. They demonstrate that urine SAM is a potent biomarker for monitoring renal function decline at early CKD stages [59].

Shih et al. [60] indicated that a high homocysteine level can be an independent risk factor for CKD in the middle-aged and elderly populations in Taiwan.

Homocysteine can contribute to ROS production by activating NADPH oxidase. These generated ROS disrupt normal cellular function, thereby contributing to kidney disease. Studies have indeed demonstrated that hyperhomocysteinemia compromises microvascular function in various organs, including the microvascular system within the kidneys [60].

S-adenosyl-L-methionine, derived from methionine, serves as the substrate for SAM-dependent methyltransferases, which catalyze the transfer of its methyl group. SAM plays a crucial role, accounting for over 90% of the methylation processes involving nucleic acids, proteins, and lipids. The reaction also produces S-adenosylhomocysteine, which, in turn, acts as an inhibitor of the methyltransferase reaction. In conditions of hyperhomocysteinemia, there is an increase in intracellular SAH, leading to the inhibition of SAM-dependent methyl transfer. High SAH levels particularly affect DNA methyltransferases, impacting the methylation status of certain genes, including the hTERT gene, which has implications for kidney function [60].

4.3 Cysteine and homocysteine in diabetes

Cysteine and homocysteine are two sulfur-containing amino acids that have been implicated in the pathogenesis of diabetes. Previous studies have shown that patients with diabetes tend to have higher levels of homocysteine compared to the general population [61].

Diabetic retinopathy is a severe microvascular complication that affects individuals with diabetes, leading to progressive damage to the retina and potentially causing vision loss. Several studies have suggested that homocysteine, a sulfur-containing amino acid, plays a significant role in the development and progression of diabetic retinopathy [61, 62]. Elevated levels of homocysteine have been linked to increased oxidative stress, mitochondrial damage, and activation of various pathways associated with the development and progression of diabetic retinopathy. Multiple mechanisms have been proposed to explain the involvement of homocysteine in diabetic retinopathy. One proposed mechanism is the activation of matrix metalloproteinase-9 by homocysteine, which leads to disruption of the blood-retinal barrier and increased vascular permeability in the retina [61]. Another proposed mechanism involves the inhibition of the transcriptional activity of nuclear factor erythroid 2-related factor 2, a key regulator of antioxidant defense systems, by elevated levels of homocysteine. This inhibition compromises the defense system’s ability to counteract increased oxidative stress, leading to further damage to retinal cells. Furthermore, it has been observed that hyperhomocysteinemia is often associated with endothelial dysfunction and inflammation, both of which are known to contribute to the development and progression of diabetic retinopathy. Several studies have investigated the potential therapeutic implications of reducing homocysteine levels in diabetic retinopathy.

Furthermore, high homocysteine levels can trigger inflammation, endoplasmic reticulum, stress, and other pathways, intensifying mitochondrial damage. The biosynthesis of S-adenosylmethionine during homocysteine metabolism from methionine further activates DNA methyltransferases, leading to alterations in the DNA methylation status of various genes implicated in mitochondrial homeostasis [63].

Wijekoon et al. [64] provided experimental evidence showcasing the direct impact of insulin and counter-regulatory hormones on the modulation of cystathionine β-synthase and betaine homocysteine methyltransferase.

Their investigations revealed that insulin exerts a regulatory influence on cystathionine β-synthase and BHMT, contributing to the intricate metabolic changes associated with diabetes mellitus. Additionally, counter-regulatory hormones were found to play a pivotal role in this regulatory network, further shaping the activities of these enzymes. The interplay between insulin and counter-regulatory hormones emerges as a crucial factor in the dysregulation of homocysteine metabolism seen in both Type 1 and Type 2 diabetes. The meta-analysis of Wang et al. [65] indicated elevated blood homocysteine levels in individuals with Type 2 diabetes mellitus (T2DM), particularly among those with diabetic nephropathy (DN) and diabetic retinopathy (DR), but the precise role of homocysteine in the development of T2DM and its associated complications remains ambiguous.

Homocysteine has been identified as closely associated with the development of diabetes mellitus. Homocysteine alone is insufficient as a predictor of diabetes mellitus. Li et al. [66] determined the relationship between the main metabolites involved in the Hcy metabolic pathway and DM. Their results revealed the detection of 13 metabolites associated with the Hcy metabolic pathway in the samples. In the DM group, the levels of Hcy, cysteine, taurine, pyridoxamine, methionine, and choline exhibited a significant increase. Notably, Hcy, choline, cystathionine, methionine, and taurine played a significant role in the probabilistic principal component analysis model. Hcy, taurine, methionine, and choline emerge as potential risk factors for diagnosing diabetes and hold promise for assessing the severity of the condition [66].

A deficiency in L-serine can contribute to elevated homocysteine levels through two mechanisms. Firstly, there is a reduced supply of N5-CH3-THF for the methylation of homocysteine, attributable to an adaptive increase in L-serine synthesis from glycine. Secondly, there is an impaired synthesis of cystathionine from L-serine and homocysteine by cystathionine β-synthase, leading to a subsequent reduction in the drainage of homocysteine from the methionine cycle to the transsulfuration pathway. This possibility is substantiated by the occurrence of hyperhomocysteinemia in humans exhibiting cystathionine β-synthase deficiency [67, 68]. Rehman et al. [33] reported decreased levels of cysteine concomitant with increased homocysteine levels in diabetes.

4.4 Cysteine and homocysteine in neurological disorders

Homocysteine is transported into the brain, and the brain has a limited capacity for Hcy metabolism. Brain tissues employ various mechanisms to reduce homocysteine levels. These mechanisms include efficient recycling through the vitamin B12-dependent methionine synthase, which is the sole enzyme in the brain responsible for converting Hcy into methionine. Additionally, catabolism occurs through cystathionine beta-synthase, leading to the formation of cystathionine—a non-noxious product that further converts into cysteine. Moreover, the brain regulates Hcy levels by exporting them to the external circulation [69].

In the brain, the accumulation of homocysteine is correlated with increased total homocysteine and S-adenosylmethionine levels in cerebrospinal fluid. Induced elevation of Hcy has been shown to induce dysfunction in endothelial and astrocytic cells, leading to altered neuronal function. Elevated Hcy levels result in heightened excitatory glutamatergic neurotransmission in various brain regions, contributing to neuronal damage. In summary, Hcy induces redox imbalance, increases oxidative stress, and triggers the production of free radicals in various cell types, including endothelial, glial, and neuronal cells, thereby contributing to several neurological disorders [70].

Both cysteine and homocysteine metabolism are linked to neurological disorders, and mitochondrial dysfunction is often observed in conditions such as Alzheimer’s disease and Parkinson’s disease.

5. Identification of current challenges and gaps in understanding cysteine and homocysteine roles

Understanding the roles of cysteine and homocysteine in various physiological processes is a current area of research. Here are some challenges and gaps in understanding these amino acids.

Both amino acids are involved in complex metabolic pathways. Cysteine is derived from methionine via homocysteine, and its metabolism involves complex interactions with various enzymes, cofactors, and regulatory molecules. Understanding the entire metabolic network and the factors that influence it is challenging.

Cysteine plays a crucial role in cellular redox homeostasis, being a key component of glutathione, an important antioxidant. The precise mechanisms by which cysteine influences redox balance in different cellular compartments and its implications for health and disease are not fully elucidated.

Homocysteine is implicated in DNA methylation, which is crucial for gene expression regulation. However, the exact mechanisms by which homocysteine influences epigenetic modifications and the specific genes affected are areas of ongoing investigation.

Elevated homocysteine levels have been associated with neurodegenerative diseases. Understanding the exact mechanisms by which homocysteine contributes to neurological disorders and whether it is a causative factor or a consequence is still an active area of research.

Homocysteine has been linked to cardiovascular diseases, but the relationship is complex. The specific mechanisms by which elevated homocysteine contributes to cardiovascular pathologies and whether interventions to lower homocysteine levels are beneficial remain areas of debate and investigation.

Cysteine and homocysteine metabolism are influenced by dietary factors, including the intake of methionine, vitamins (B6, B12, folate), and other nutrients. The interplay between diet and the regulation of cysteine and homocysteine levels is not fully understood, especially in diverse populations with different dietary patterns.

Both cysteine and homocysteine can interact with various molecules and participate in diverse cellular processes. Understanding the wide-ranging interactions and their implications for cellular function and health requires further investigation.

Identifying reliable biomarkers related to cysteine and homocysteine metabolism for diagnostic and prognostic purposes remains an ongoing challenge. Additionally, determining the clinical significance of alterations in these amino acids and developing targeted therapies is an area of active research.

6. Conclusions

The evolving nature of our understanding of cysteine and homocysteine in pathological processes reflects the dynamic and interdisciplinary nature of scientific research. Scientific research is a continuous process, and new studies are regularly published, providing novel insights into the roles of cysteine and homocysteine in various pathological processes. Ongoing research may uncover previously unknown connections, mechanisms, and functions related to these amino acids. Advances in analytical techniques and technologies contribute to our ability to study cysteine and homocysteine at a more detailed and nuanced level. Techniques such as metabolomics, proteomics, and advanced imaging methods allow researchers to explore these molecules’ functions and interactions in greater depth.

The role of homocysteine in epigenetic modifications and gene regulation is an evolving area of interest. Continued research may reveal additional details about how homocysteine influences gene expression and the implications for various diseases.

Ongoing clinical trials and translational research contribute to the translation of basic scientific knowledge into practical applications for diagnosis, treatment, and prevention. As these studies progress, our understanding of the clinical significance of cysteine and homocysteine in specific pathological conditions may evolve. Collaboration between researchers from different fields, such as biochemistry, genetics, nutrition, and clinical medicine, continues to enrich our understanding of cysteine and homocysteine. Interdisciplinary approaches help address complex questions and provide a more comprehensive view of their roles in pathology.

Given the dynamic nature of the scientific inquiry, it is crucial to stay informed about the latest research findings and advancements in the field to appreciate the evolving landscape of our understanding of cysteine and homocysteine in pathological processes.

Conflict of interest

The authors declare no conflict of interest.