Pathways

Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.

Metabolites of Sarecycline are predicted with biotransformer.

Scopolamine is a belladonna alkaloid with anticholinergic effects indicated for the treatment of nausea and vomiting associated with motion sickness and postoperative nausea and vomiting (PONV). It can be found under the brand names Donnatal, Phenohytro, and Transderm Scop. Acetylcholine (ACh) is a neurotransmitter that can signal through ligand-gated cation channels (nicotinic receptors) and G-protein-coupled muscarinic receptors (mAChRs). ACh signalling via mAChRs located in the central nervous system (CNS) and periphery can regulate smooth muscle contraction, glandular secretions, heart rate, and various neurological phenomena such as learning and memory. mAChRs can be divided into five subtypes, M1-M5, expressed at various levels throughout the brain. Also, M2 receptors are found in the heart and M3 receptors in smooth muscles, mediating effects apart from the direct modulation of the parasympathetic nervous system. While M1, M3, and M5 mAChRs primarily couple to Gq proteins to activate phospholipase C, M2 and M4 mainly couple to Gi/o proteins to inhibit adenylyl cyclase and modulate cellular ion flow. This system, in part, helps to control physiological responses such as nausea and vomiting. The significance of these observations to scopolamine's current therapeutic indications of preventing nausea and vomiting is unclear but is linked to its anticholinergic effect and ability to alter signalling through the CNS associated with vomiting. Possible side effects of using scopolamine may include disorientation, dry mouth, drowsiness, and sweating.

Metabolites of Scopolamine are predicted with biotransformer.

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