Pathways

Undeca-7,9-dienoylcarnitine is an acylcarnitine. The general role of acylcarnitines is to transport acyl-groups, organic acids and fatty acids, from the cytoplasm into the mitochondria so that they can be broken down to produce energy. As part of this process, undeca-7,9-dienoic acid is first transported into the cell via the long-chain fatty acid transport protein 1 (FATP1). Once inside the cell it undergoes a reaction to form an acyl-CoA derivative called undeca-7,9-dienoyl-CoA. This reaction is facilitated by the long-chain fatty-acid CoA ligase 1 protein, which adds a CoA moiety to appropriate acyl groups. Many acyl-CoA groups will then further react with other zwitterionic compounds such as carnitine (to form acylcarnitines) and amino acids (to form acyl amides). The carnitine needed to form acylcarnitines inside the cell is transported into the cell by the organic cation/carnitine transporter 2. In forming an acylcarnitine derivative, undeca-7,9-dienoyl-CoA reacts with L-carnitine to form undeca-7,9-dienoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the undeca-7,9-dienoylcarnitine is moved into the mitochondrial intermembrane space. Following the reaction, the newly synthesized acylcarnitine is transported into the mitochondrial matrix by a mitochondrial carnitine/acylcarnitine carrier protein found in the mitochondrial inner membrane. Once in the matrix, undeca-7,9-dienoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form undeca-7,9-dienoyl-CoA and L-carnitine. Undeca-7,9-dienoyl-CoA then enters into the mitochondrial beta-oxidation pathway to form aceytl-CoA. Acetyl-CoA can go on to enter the TCA cycle, or it can react with L-carnitine to form L-acetylcarnitine in a reaction catalyzed by Carnitine O-acetyltransferase. This reaction can occur in both directions, and L-acetylcarnitine and CoA can react to form acetyl-CoA and L-carnitine in certain circumstances. Finally, acetyl-CoA in the cytosol can be catalyzed by acetyl-CoA carboxylase 1 to form malonyl-CoA, which inhibits the action of carnitine O-palmitoyltransferase 1, thereby preventing undeca-7,9-dienoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

Undecanedioylcarnitine is an acylcarnitine. The general role of acylcarnitines is to transport acyl-groups, organic acids and fatty acids, from the cytoplasm into the mitochondria so that they can be broken down to produce energy. As part of this process, undecanedioic acid is first transported into the cell via the long-chain fatty acid transport protein 1 (FATP1). Once inside the cell it undergoes a reaction to form an acyl-CoA derivative called undecanedioyl-CoA. This reaction is facilitated by the long-chain fatty-acid CoA ligase 1 protein, which adds a CoA moiety to appropriate acyl groups. Many acyl-CoA groups will then further react with other zwitterionic compounds such as carnitine (to form acylcarnitines) and amino acids (to form acyl amides). The carnitine needed to form acylcarnitines inside the cell is transported into the cell by the organic cation/carnitine transporter 2. In forming an acylcarnitine derivative, undecanedioyl-CoA reacts with L-carnitine to form undecanedioylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the undecanedioylcarnitine is moved into the mitochondrial intermembrane space. Following the reaction, the newly synthesized acylcarnitine is transported into the mitochondrial matrix by a mitochondrial carnitine/acylcarnitine carrier protein found in the mitochondrial inner membrane. Once in the matrix, undecanedioylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form undecanedioyl-CoA and L-carnitine. Undecanedioyl-CoA then enters into the mitochondrial beta-oxidation pathway to form aceytl-CoA. Acetyl-CoA can go on to enter the TCA cycle, or it can react with L-carnitine to form L-acetylcarnitine in a reaction catalyzed by Carnitine O-acetyltransferase. This reaction can occur in both directions, and L-acetylcarnitine and CoA can react to form acetyl-CoA and L-carnitine in certain circumstances. Finally, acetyl-CoA in the cytosol can be catalyzed by acetyl-CoA carboxylase 1 to form malonyl-CoA, which inhibits the action of carnitine O-palmitoyltransferase 1, thereby preventing undecanedioylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

Adapalene is a third-generation topical retinoid with anti-comedogenic, comedolytic, and anti-inflammatory properties used to treat acne vulgaris in adolescents and adults. Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug. Adapalene PIS1M1 is a metabolite of Adapalene predicted with biotransformer.

Metabolites of Adapalene are predicted with biotransformer.

Adefovir dipivoxil is an ester prodrug of adefovir, a nucleotide analogue used in the treatment of chronic hepatitis B. Adefovir dipivoxil is taken up into the liver cell and is cleaved into adefovir by intracellular esterases. Adefovir is subsequently phosphorylated first by adenylate kinases and then by nucleoside diphosphate kinases into adefovir diphosphate. Adefovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP) and competes with dATP for binding to the viral DNA polymerase and subsequent incorporation into the growing DNA strand. Once incorporated into the DNA, adefovir causes chain termination, thus preventing viral replication.

Adefovir dipivoxil is a nucleotide analog used to treat chronic hepatitis B virus (HBV). When HBV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HBV viruses bud from the cell. Adefovir dipivoxil enters the cell and is metabolized to release adefovir by carboxylesterase enzyme. Adefovir is converted into adefovir monophosphate by adenylate kinases. Nucleoside diphosphate kinases then convert adefovir monophosphate into adefovir diphosphate. Adefovir diphosphate is an analog of deoxyadenosine-5'-triphosphate (dATP). Adefovir diphosphate inhibits the activity of HBV reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Adefovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once adefovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Adefovir dipivoxil is an ester prodrug of adefovir, a nucleotide analogue used in the treatment of chronic hepatitis B. Adefovir dipivoxil is taken up into the liver cell and is cleaved into adefovir by intracellular esterases. Adefovir is subsequently phosphorylated first by adenylate kinases and then by nucleoside diphosphate kinases into adefovir diphosphate. Adefovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP) and competes with dATP for binding to the viral DNA polymerase and subsequent incorporation into the growing DNA strand. Once incorporated into the DNA, adefovir causes chain termination, thus preventing viral replication.