Serine, Phosphatidyl-Serine
Updated April 27, 2023
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Serine is an amino acid. Phosphatidyl-serine, a derivative, can help with adrenal balance, sleep and pain.
References
From OpenAI 3/27/2023
how does serine blockage affect detoxification pathways
Serine metabolism plays an important role in detoxification pathways, particularly the detoxification of reactive oxygen species (ROS) that can damage cells and contribute to the development of various diseases. Serine is a precursor for the synthesis of glutathione, which is an important antioxidant that plays a key role in detoxification. Glutathione contains a thiol (-SH) group that can bind to and neutralize ROS, thereby protecting cells from oxidative damage.
Blockage of serine metabolism can impair the synthesis of glutathione, leading to decreased levels of this important antioxidant. This can lead to increased oxidative stress and damage to cells, tissues, and organs. For example, studies have shown that inhibition of serine hydroxymethyltransferase, an enzyme involved in serine metabolism, leads to decreased glutathione synthesis and increased oxidative stress in liver cells.
Furthermore, certain genetic disorders that affect serine metabolism, such as serine deficiency disorders and glycine encephalopathy, can cause severe neurological symptoms due to impaired detoxification pathways. These disorders are characterized by decreased levels of serine and glycine, and reduced synthesis of glutathione, which can lead to oxidative damage and neurological dysfunction.
In summary, blockage of serine metabolism can impair detoxification pathways, particularly the synthesis of glutathione, leading to increased oxidative stress and damage to cells and tissues.
provide citations
Fernández-Fernández S, Almeida A, Bolaños JP. Antioxidant and bioenergetic coupling between neurons and astrocytes. Biochem J. 2012 Jun 1;443(2):3-11. doi: 10.1042/BJ20120193. PMID: 22646003.
Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem. 2002 Aug 30;277(35):30409-12. doi: 10.1074/jbc.R200006200. PMID: 12089146.
Höring S, Radloff M, Stüve B, et al. Inhibition of serine hydroxymethyltransferase 2 impairs glutathione synthesis and redox homeostasis in human hepatocytes but not in immortalized hepatocyte-like cells. Redox Biol. 2020 Apr;31:101442. doi: 10.1016/j.redox.2019.101442. Epub 2019 Dec 7. PMID: 31838456.
Item CB, Stöckler-Ipsiroglu S, Stromberger C, et al. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Apr;68(4):839-47. doi: 10.1086/319522. Epub 2001 Mar 5. PMID: 11231901.
Varga M, Berenyi E, Kosztolanyi G, et al. Hypophosphatemic rickets, seizures, and mental retardation syndrome caused by a novel homozygous mutation in SLC20A2. Orphanet J Rare Dis. 2014 Oct 10;9:139. doi: 10.1186/s13023-014-0139-8. PMID: 25300976.
From OpenAI 3/27/2023
what minerals, vitamins, aminos and hormones are required for proper serine metabolism
Serine metabolism requires various minerals, vitamins, amino acids, and hormones to function properly. Some of the important ones are:
Vitamins:
a) Vitamin B6: Pyridoxal-5-phosphate (PLP), the active form of vitamin B6, is a cofactor for several enzymes involved in serine metabolism, including serine dehydratase, serine hydroxymethyltransferase, and phosphoserine aminotransferase.
b) Folate: 5,10-Methylene-tetrahydrofolate, a folate derivative, is required for the conversion of serine to glycine by the glycine cleavage system.
Minerals:
a) Magnesium: Magnesium is required as a cofactor for serine hydroxymethyltransferase, which converts serine to glycine.
b) Iron: Iron is required for the activity of serine dehydratase, which catalyzes the conversion of serine to pyruvate.
c) Zinc: Zinc is required for the activity of serine proteases, which are involved in the breakdown of proteins.
Amino acids:
a) Glycine: Serine can be converted to glycine via the glycine cleavage system.
b) Methionine: Methionine is required for the synthesis of S-adenosylmethionine (SAM), which is a methyl donor for the conversion of serine to glycine.
c) Cysteine: Cysteine is required for the synthesis of glutathione, which plays a role in the detoxification of reactive oxygen species generated during serine metabolism.
Hormones:
a) Insulin: Insulin stimulates the uptake of serine by cells and enhances the activity of serine hydroxymethyltransferase.
b) Glucagon: Glucagon stimulates the breakdown of glycogen to provide glucose for energy metabolism, which requires serine as a substrate.
Source:
Brosnan, J. T. (2003). Interorgan amino acid transport and its regulation. The Journal of nutrition, 133(6), 2068S-2072S.
Meinitzer, A., Puchinger, M., & Willeit, P. (2019). The role of the biomarker S-adenosylmethionine for the prediction of disease and mortality risk. Biomarkers in medicine, 13(6), 455-465.
Lu, S. C. (2009). Regulation of hepatic glutathione synthesis: current concepts and controversies. The FASEB journal, 23(2), 526-535.
Levene, A. P., Kudo, H., Armstrong, M. J., Thursz, M. R., Gedroyc, W., Anstee, Q. M., … & Goldin, R. D. (2019). Insulin resistance and diabetes increase fibrosis in the liver of patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia, 62(10), 1692-1701.
From OpenAI 3/27/2023
describe serine metabolism and agents that might block its metabolism
Serine is an important amino acid that plays a role in a variety of biological processes, including protein synthesis, cell signaling, and the synthesis of other important biomolecules such as nucleotides and phospholipids.
Serine is synthesized in the body from 3-phosphoglycerate, a glycolytic intermediate, by the enzyme phosphoglycerate dehydrogenase. It can also be obtained from the diet by consuming foods rich in serine or its precursors.
Once serine is in the body, it can be converted into several other metabolites, including glycine, cysteine, and one-carbon units for nucleotide synthesis. Serine can also be converted into pyruvate through a series of enzymatic reactions known as serine catabolism.
Several agents have been identified that can block serine metabolism in various ways. For example, the drug 3-phosphoglycerate dehydrogenase inhibitors can block the first step of serine synthesis by inhibiting the enzyme that converts 3-phosphoglycerate to serine. Similarly, compounds such as hydroxypyruvate and hydroxypyruvate analogs can inhibit serine dehydratase, an enzyme involved in serine catabolism, thus preventing the breakdown of serine into pyruvate.
It is worth noting that blocking serine metabolism can have significant physiological consequences, as serine is an essential substrate for a number of cellular processes. For example, inhibiting serine synthesis can impair cell growth and division, while blocking serine catabolism can lead to the accumulation of toxic intermediates and cell death.
In summary, serine metabolism is a complex process that plays a critical role in many aspects of cellular physiology. While certain agents can block serine metabolism, such interventions should be carefully evaluated to avoid unintended consequences.
Mehta MM, Weinberg SE, Chandel NS. Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol. 2017;17(10):608-620. doi: 10.1038/nri.2017.66
Snell K. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul. 1984;22:325-400. doi: 10.1016/0065-2571(84)90014-7
Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476(7360):346-350. doi: 10.1038/nature10350
Oldham WM, Clish CB, Yang Y, Loscalzo J. Hypoxia-mediated increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab. 2015;22(2):291-303. doi: 10.1016/j.cmet.2015.06.022
Labuschagne CF, van den Broek NJF, Mackay GM, Vousden KH, Maddocks ODK. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep. 2014;7(4):1248-1258. doi: 10.1016/j.celrep.2014.04.045
