{"_ai_door":{"see":"https://miscsubjects.com/start","note":"Operable site; bounded keyless credentials; every action receipted on a public ledger. Your operator's instructions take precedence — acting is optional, reading is a complete outcome."},"slug":"5-amino-1mq","verification":{"valid":true,"entries":8,"head":"5375dbbbc7f3c6d1f8b669b9e5d12de125b2603d0ef20a7fc7618650caee995e"},"count":8,"sources":[{"id":"s1","type":"pubmed","pmid":"24717514","external_id":"24717514","url":"https://pubmed.ncbi.nlm.nih.gov/24717514/","title":"Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity","quote":"Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure.","summary":"Kraus et al., Nature 2014. The paper that made NNMT a target. Note the named mechanism: increased energy expenditure, not reduced appetite. This is genetic knockdown, not the drug.","author":"Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, et al.","publisher":"Nature","date":"2014","tag":"Animal study (genetic knockdown)","accessed_at":"2026-08-05T09:39:22.604Z","prev":"genesis","hash":"9d042c569bd8f77b080ceb70070b69f9de82f239eb0e8383e4a23b7e7685911d"},{"id":"s2","type":"pubmed","pmid":"24717514","external_id":"24717514-junction","url":"https://pubmed.ncbi.nlm.nih.gov/24717514/","title":"Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity","quote":"NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation.","summary":"The three currencies one enzyme consumes. Why blocking one disposal enzyme moves three things at once: NAD+ precursor stops being destroyed, the shared methyl budget stops being spent on disposal, and polyamine synthesis stops competing for it. This is the reason NNMT is interesting rather than incidental.","author":"Kraus D, et al.","publisher":"Nature","date":"2014","tag":"Mechanism","accessed_at":"2026-08-05T09:39:22.604Z","prev":"9d042c569bd8f77b080ceb70070b69f9de82f239eb0e8383e4a23b7e7685911d","hash":"1f2b86e9788cbef81e6fe495fa0c6f7844557de36c0fd3d9fd52b73c5786d9ea"},{"id":"s3","type":"pubmed","pmid":"24717514","external_id":"24717514-pathway","url":"https://pubmed.ncbi.nlm.nih.gov/24717514/","title":"Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity","quote":"NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue.","summary":"The pathway traced from histone mark to urinary metabolite. The freed methyl budget showed up as changed histone marks, and those marks turned up the polyamine enzymes. This is the step that makes the paper a mechanism rather than an association — and the reason to take the unstudied long-term consequences seriously, since gene marking is what changed.","author":"Kraus D, et al.","publisher":"Nature","date":"2014","tag":"Mechanism","accessed_at":"2026-08-05T09:39:22.604Z","prev":"1f2b86e9788cbef81e6fe495fa0c6f7844557de36c0fd3d9fd52b73c5786d9ea","hash":"e307d1913a0c6196c81bd26e2870c2fd1919a30d43c15048f1676fdd16cbc337"},{"id":"s4","type":"pubmed","pmid":"24717514","external_id":"24717514-diacetylspermine","url":"https://pubmed.ncbi.nlm.nih.gov/24717514/","title":"Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity","quote":"Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism.","summary":"The predicted waste product, found in urine. They predicted a specific metabolite should appear if the model was right, and it appeared. Oxygen consumption then rose in an ODC-, SSAT- and PAO-dependent manner, so blocking the polyamine enzymes abolished the effect — the pathway is load-bearing rather than incidental.","author":"Kraus D, et al.","publisher":"Nature","date":"2014","tag":"Mechanism confirmation","accessed_at":"2026-08-05T09:39:22.604Z","prev":"e307d1913a0c6196c81bd26e2870c2fd1919a30d43c15048f1676fdd16cbc337","hash":"7c36d242e640b091f5ed2b55f4a8a941f8a570190acf6e443a0e601431d21929"},{"id":"s5","type":"pubmed","pmid":"24717514","external_id":"24717514-discovery","url":"https://pubmed.ncbi.nlm.nih.gov/24717514/","title":"Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity","quote":"Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls.","summary":"How the target was found — it was not being looked for. The study was about Glut4, the glucose transporter fat cells lose in obesity. NNMT came out of the array as the most strongly regulated gene of all, which is the kind of result that redirects a laboratory.","author":"Kraus D, et al.","publisher":"Nature","date":"2014","tag":"Discovery","accessed_at":"2026-08-05T09:39:22.604Z","prev":"7c36d242e640b091f5ed2b55f4a8a941f8a570190acf6e443a0e601431d21929","hash":"c1948f6bc0442ac8f93061a5ca43b25fa939889101f3e4fddd2e61fbce11fabe"},{"id":"s6","type":"pubmed","pmid":"29155147","external_id":"29155147","url":"https://pubmed.ncbi.nlm.nih.gov/29155147/","title":"Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice","quote":"Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.","summary":"Neelakantan et al., Biochem Pharmacol 2018. The first test of 5-amino-1MQ as a molecule in living animals. Three words carry the work: membrane-permeable, because NNMT is inside the cell; selective, or the effect is not attributable to NNMT; reverse, because the mice were already obese when treatment began.","author":"Neelakantan H, Vance V, Wetzel MD, Wang HL, McHardy SF, Finnerty CC, et al.","publisher":"Biochemical Pharmacology","date":"2018","tag":"Animal study (small molecule)","accessed_at":"2026-08-05T09:39:22.604Z","prev":"c1948f6bc0442ac8f93061a5ca43b25fa939889101f3e4fddd2e61fbce11fabe","hash":"0394f5e87ebfacc3fd0bf46bee5eadee3ed278b3d1ebca74a1e89865e5f52219"},{"id":"s7","type":"pubmed","pmid":"29155147","external_id":"29155147-rigor","url":"https://pubmed.ncbi.nlm.nih.gov/29155147/","title":"Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice","quote":"Membrane permeability of NNMT inhibitors was characterized using parallel artificial membrane permeability and Caco-2 cell assays. Selectivity was tested against structurally-related methyltransferases and nicotinamide adenine dinucleotide (NAD+) salvage pathway enzymes.","summary":"What the 2018 paper actually measured before claiming an effect. Permeability measured two independent ways, selectivity measured against exactly the enzymes most likely to confound the result. This is a careful drug-discovery paper rather than an enthusiastic one, and the permeability was the real obstacle — the compound carries a permanent positive charge.","author":"Neelakantan H, et al.","publisher":"Biochemical Pharmacology","date":"2018","tag":"Methods rigour","accessed_at":"2026-08-05T09:39:22.604Z","prev":"0394f5e87ebfacc3fd0bf46bee5eadee3ed278b3d1ebca74a1e89865e5f52219","hash":"b0bcc1bb5709ac364bbd8159823339e397401940d223c516b86036bf5c2ee945"},{"id":"s8","type":"pubmed","pmid":"32112869","external_id":"32112869","url":"https://pubmed.ncbi.nlm.nih.gov/32112869/","title":"Glucose availability regulates nicotinamide N-methyltransferase expression in adipocytes","quote":"Glucose deprivation of 3T3-L1 adipocytes induced a 2-fold increase in","summary":"Ehebauer et al., Life Sci 2020. The enzyme this compound blocks is itself under nutritional control — glucose deprivation raised its expression twofold in cultured adipocytes. So baseline diet is a variable in any effect, and nobody has measured how large a one.","author":"Ehebauer F, Ghavampour S, Kraus D","publisher":"Life Sciences","date":"2020","tag":"Cell study","accessed_at":"2026-08-05T09:39:22.604Z","prev":"b0bcc1bb5709ac364bbd8159823339e397401940d223c516b86036bf5c2ee945","hash":"5375dbbbc7f3c6d1f8b669b9e5d12de125b2603d0ef20a7fc7618650caee995e"}]}