Pathways

Metabolites of Metaraminol are predicted with biotransformer.

Metabolites of Metaxalone are predicted with biotransformer.

Metabolites of Metergoline are predicted with biotransformer.

Metformin is a biguanide drug used in conjunction with diet and exercise for glycemic control in type 2 diabetes mellitus and used off-label for insulin resistance in polycystic ovary syndrome (PCOS). After ingestion, the organic cation transporter-1 (OCT1) is responsible for the uptake of metformin into hepatocytes (liver cells). Metformin inhibits complex I of the mitochondrial respiratory chain, preventing ATP production and increasing ADP: ATP and AMP:ATP ratios in the cytosol. High AMP:ATP ratio inhibit fructose 1,6-bisphosphate, preventing gluconeogenesis. High AMP:ATP ratios also inhibits cAMP production by inhibiting adenylate cyclase. cAMP is responsible for activating protein kinase A (PKA). PKA inhibits 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and pyruvate kinase and driving gluconeogenesis. PKA may also activate transcription factors (cAMP response element binding protein) which induce transcription of the genes encoding the gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. By preventing PKA activation, this drives glycolysis over gluconeogenesis. High AMP:ATP ratio also activates AMP kinase (AMPK). Metformin also activates AMPK via lysosomal mechanisms. AMPK induces cAMP breakdown, to further prevent PKA activation. AMPK also inhibit transcription factors preventing transcription of the genes encoding the gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. AMPK also affect fats by inhiting Acetyl-coA carboxylase, thereby inhibiting fat synthesis and promoting fat oxidation instead, thus reducing hepatic lipid stores and enhancing hepatic insulin sensitivity. Overall, metformin improves insulin sensitivity by increasing fatty acid oxidation, reducing fatty acid synthesis and inhbiting gluconeogenesis. This leads to lower blood glucose and triglycerides level, and is effective in controlling diabetes. The major side effect of metformin include gastrointestinal effects such as diarrhea, abdominal pain, nausea, anorexia, metallic taste.

Metformin is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Metformin passes through the liver and is then excreted from the body mainly through the kidney.

Methacholine is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Methacholine passes through the liver and is then excreted from the body mainly through the kidney.