Pathways

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occasion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. It's mechanism of action it to bind selectively bind to the sodium dependent serotonin transporter and blocking the recycling of serotonin from the synapse. As with other SSRIs, it showed weak effects on norepinephrine and dopamine neuronal reuptake. As serotonin accumulates it enhances the serotonergic function of the 5-hydroxytryptamine 1A receptor leading to decreased anxiety and depressive moods.

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occasion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. It's mechanism of action it to bind selectively bind to the sodium dependent serotonin transporter and blocking the recycling of serotonin from the synapse. As with other SSRIs, it showed weak effects on norepinephrine and dopamine neuronal reuptake. As serotonin accumulates it enhances the serotonergic function of the 5-hydroxytryptamine 1A receptor leading to decreased anxiety and depressive moods.

Metabolites of Fluvoxamine are predicted with biotransformer.

The biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate. This product goes on to a one carbon pool by folate pathway.

The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway

The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway

Folate biosynthesis is a pathway by which pterin and pABA precursors form tetrahydrofolate, an essential cofactor that takes part in various enzymatic reactions as a carrier for one-carbon units. Although tetrahydrofolate is synthesized in the mitochondrial matrix, the pterin and pABA branches occur in the cytosol and the chloroplast, respectively. The first reaction in the pABA branch is catalyzed by aminodeoxychorismate synthase (ADCS) whereby chorismate and L-glutamine is converted to aminodeoxychorismate and L-glutamic acid. The second reaction in the pABA branch is catalyzed by aminodeoxychorismate lyase (ADCL) whereby aminodeoxychorismate is converted to pABA, pyruvic acid, and a hydrogen ion. pABA then diffuses out of the chloroplast and into the mitochondrial matrix to be used in folate biosynthesis. From the pterin branch, hydroxymethyldihydropterin (HMDHP) is pumped into the mitochondria by a yet to be discovered HMDHP transporter. The bifunctional enzyme hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS), which requires magnesium as a cofactor, catalyzes consecutive steps that unites the pABA and pterin branches. The HPPK domain uses ATP to diphosphorylate HMDHP to HMDHP pyrophosphate, releasing AMP and a hydrogen ion in the process. The DHPS domain incorporates pABA, diffused out from the chloroplast, to form dihydropteroate and a diphosphate. Next, dihydrofolate (DHF) synthase catalyzes the ATP hydrolysis powered conversion of dihydropteroate and L-glutamic acid to dihydrofolate. Finally, the DHFR domain of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) reduces dihydrofolate to tetrahydrofolate with the help of NADPH and a hydrogen ion.

Hereditary folate malabsorption, also known as folic acid transport defect, is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the folate metabolism pathway. It is caused by a defect in the SLC46A1 gene that encodes the proton-coupled folate transporter protein which is responsible for folate uptake from the intestines. Hereditary folate malabsorption is characterized by low concentrations of folate in the serum and cerebrospinal fluid. Symptoms include feeding difficulties and failure to thrive and anemia, as well as potential neurological issues such as seizures and developmental delays. When infants are born with hereditary folate malabsorption, there are initially few signs, as folate is provided across the placenta, but after birth, folate absorption is inhibited and these symptoms begin to be exhibited. Treatment for hereditary folate malabsorption includes intramuscular or oral doses of reduced folates to bring cerebrospinal fluid folate levels to a normal range, as well as blood transfusions if severe anemia is present. It is estimated that hereditary folate malabsorption affects less than 1 in 1,0000,000 people, with only approximately 30 reported cases.

Hereditary folate malabsorption, also known as folic acid transport defect, is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the folate metabolism pathway. It is caused by a defect in the SLC46A1 gene that encodes the proton-coupled folate transporter protein which is responsible for folate uptake from the intestines. Hereditary folate malabsorption is characterized by low concentrations of folate in the serum and cerebrospinal fluid. Symptoms include feeding difficulties and failure to thrive and anemia, as well as potential neurological issues such as seizures and developmental delays. When infants are born with hereditary folate malabsorption, there are initially few signs, as folate is provided across the placenta, but after birth, folate absorption is inhibited and these symptoms begin to be exhibited. Treatment for hereditary folate malabsorption includes intramuscular or oral doses of reduced folates to bring cerebrospinal fluid folate levels to a normal range, as well as blood transfusions if severe anemia is present. It is estimated that hereditary folate malabsorption affects less than 1 in 1,0000,000 people, with only approximately 30 reported cases.