Experimental studies with antioxidants
Ronald R. Watson in NUTRIENTS and FOODS in AIDS, 2017
The cause of cysteine deficiency in AIDS is not known. Cysteine is a nonessential amino acid, normally synthesized in the liver from the conversion of methionine through the action of the enzyme cystathionine synthase, which requires pyridoxine (vitamin B6) as a cofactor. Under conditions of pyridoxine deficiency, cysteine may be required as an essential amino acid. Pyridoxine deficiency was reported in about one-half of persons with asymptomatic HIV infection.23 HIV-infected persons with CD4 deficiencies also have 5 to 6 times higher levels of serum glutamate than uninfected controls.22 Extracellular glutamate has been shown to compete with the transport of cystine into macrophages resulting in a reduced capacity of these cells to release cysteine and its supply to lymphocytes.22 These abnormalities may contribute to the cysteine and GSH deficiencies prevalent in AIDS.
Prenatal and Genetic Magnesium Deficiency in Cardiomyopathy: Possible Vitamin and Trace Mineral Interactions
Fima Lifshitz in Childhood Nutrition, 2020
Homocystinuria and Cardiomyopathy; Interaction of Nutrient Deficiencies?—Pyridoxine-Dependence of Homocystinurics: One of the conditions listed as being associated with CMP is homocystinuria,99 predominantly a vitamin Independent disorder.220–222 There are several metabolic abnormalities that give rise to homocystinuria, the most common of which is a Mendelian recessive trait that causes deficient activity of cystathionine beta-synthase, an enzyme that contains pyridoxal phosphate.220 Almost half of the patients respond to very high dosage pyridoxine (up to 300 times more pyridoxine than is needed for correction of a simple deficiency; they may have slight (residual) activity of this enzyme.220–221 Those with a more complete deficiency of the enzyme, or with a metabolic block after formation of cystathionine, also require additional dietary modification and/or supplementation.
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Multiple infarcted areas are seen in the brain of homocystinuric patients. Cystathionine, present normally in high concentrations, is absent, indicating the local involvement of the missing enzyme. Primary structural changes are found in blood vessels independent of their diameter. Intimal thickening and fibrosis are mostly characteristic and major branches with fraying elastic fibers are also found in the aorta. Arterial and venous thomboses occur in many organs. It may be that homocysteine is responsible for the vascular lesion although the mechanism has not been revealed. The mental defect can be associated with cystine or cystathionine deficiency or excess methionine. The way how brain damage develops is still obscure since it is not yet clear what the role of cystathionine is, other than as intermediate in cysteine synthesis.
Expression of pulmonary arterial elastin in rats with hypoxic pulmonary hypertension using H2S
Published in Journal of Receptors and Signal Transduction, 2020
Juan Chen, Haizhou Zhang, Wancheng Yu, Lei Chen, Zhengjun Wang, Tao Zhang
Recently, it has been confirmed in clinical trials that CO and NO can reduce the elevated pulmonary artery pressure in PHP rats, and can further alleviate the structural reconstruction of hypoxia-induced pulmonary vascular. H2S is a new gas messenger molecule that has been recently discovered. It appears under the catalysis of cysteine by cystathionine-β-synthase and cysteine transferase. The CSE gene is expressed in the pulmonary artery, aorta, caudal artery, and mesenteric artery, while CBS gene is mainly expressed in the nervous system. According to relevant research, endogenous H2S can regulate vascular tension by directly opening the K+-ATP channel on the vascular smooth muscle cell membrane. This result indicates that H2S is a new endogenous gas messenger that allows molecules to actively participate in the formation of pulmonary hypertension. Studies have verified that exogenous injection of H2S in HPH rats can alleviate hypoxia-induced pulmonary hypertension, which demonstrates that H2S has a significant inhibitory effect on the formation of HPH [17–19].
The role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis; anti- or pro-inflammatory cells?
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Misagh Rajabinejad, Farhad Salari, Ali Gorgin Karaji, Alireza Rezaiemanesh
MDSCs can suppress the immune responses via different mechanisms, including the production of Arg1, nitration of the TCR or chemokines and activation of inducible NO synthase (iNOS). In addition, MDSCs can inhibit T cell and macrophage activity by downregulating the production of the type 1 cytokines, such as IL-12 and upregulating the production of ROS, prostaglandin (PG) E2 (through cyclooxygenase 2) and a number of anti-inflammatory cytokines [27,29]. Arginine (Arg), a non-essential amino acid, plays a major role in different biological processes, including the immune responses [69]. Arg1 and cationic amino acid transporter (CAT2B), which are expressed by MDSCs, can lead to depletion of Arg from the environment and, in turn, T cell dysfunction. Low Arg levels induce loss of the CD3ζ chain, inhibition of the T cell proliferation (by cyclin D3 mRNA instability) and diminish of cytokine production [70]. MDSCs also use other mechanisms to inhibit the innate and adaptive immunity. They sequester cysteine that is an essential amino acid for the T cell activation and function. T cells do not have cystathionine which is necessary for the conversion of intracellular methionine to cysteine. Moreover, they do not have the xCT chain of the xc − transporter. Therefore, T cell needs the extracellular cysteine produced by other cells. Cysteine is imported by T cells through the alanine-serine-cysteine (ASC) neutral amino acid transporter [71].
Givosiran for the treatment of acute hepatic porphyria
Published in Expert Review of Clinical Pharmacology, 2022
Some authors have reported, together with homocysteine, a concurrent increase in methionine levels [64,67], which may hint at a specific dysfunction of cystathionine beta-synthase (CBS), a vitamin B6–dependent enzyme that relies on heme for regulatory functions (the trans-sulfuration pathway of homocysteine catabolism starts with CBS). In principle, the inhibitory action of givosiran on the first and rate-limiting enzyme of heme biosynthesis could have an impact on the non-erythropoietic routes of heme utilization. In this case, even though vitamin B6 supplementation, used alone, may be effective in increasing CBS activity, a more complete supplementation therapy may provide a beneficial enhancement of both routes of homocysteine catabolism (trans-sulfuration and remethylation). Moreover, as the metabolism of amino acids and heme biosynthesis are complexly intertwined, it cannot be excluded that hyperhomocysteinemia is the result of more complex interactions that may benefit from a more complete integration of vitamins and cofactors. While further studies are needed before reaching consensus recommendations, it should be considered that all patients eligible for givosiran be screened for basal homocysteine levels and hyperhomocysteinemia-related vitamin status before starting treatment and periodically while on treatment with givosiran [65,68]. Adequate supplementation therapy can be considered in cases of hyperhomocysteinemia.
Related Knowledge Centers
- Cysteine
- Cysteine Dioxygenase
- Homocysteine
- Taurine
- Transsulfuration Pathway
- Cystathionine Gamma-Lyase
- Sulfinoalanine Decarboxylase
- Hypotaurine
- Glutamate–Cysteine Ligase
- Glutathione Synthetase