Pathways

Acute intermittent porphyria (AIP), also called Swedish porphyria, is a rare inborn error of metabolism (IEM) and autosomal dominant disorder of heme biosynthesis caused by a defective HMBS gene. The HMBS gene codes for the protein hydroxymethylbilane synthase (porphobilinogen deaminase) which catalyzes the synthesis of porphobilinogen into hydroxymethylbilane. This disorder is characterized by a large accumulation of 5-aminolevulinic acid or porphobilinogen in both urine and serum. Most patients are asymptomatic between attacks. Symptoms of the disorder include abdominal pain, constipation, vomiting, hypertension, muscle weakness, seizures, delirium, coma, and depression. Treatment involves undertaking a high-carbohydrate diet and, during severe attacks, a glucose 10% infusion. It is estimated that AIP affects 5.9 per 1 000 000 people.

Acute intermittent porphyria (AIP), also called Swedish porphyria, is a rare inborn error of metabolism (IEM) and autosomal dominant disorder of heme biosynthesis caused by a defective HMBS gene. The HMBS gene codes for the protein hydroxymethylbilane synthase (porphobilinogen deaminase) which catalyzes the synthesis of porphobilinogen into hydroxymethylbilane. This disorder is characterized by a large accumulation of 5-aminolevulinic acid or porphobilinogen in both urine and serum. Most patients are asymptomatic between attacks. Symptoms of the disorder include abdominal pain, constipation, vomiting, hypertension, muscle weakness, seizures, delirium, coma, and depression. Treatment involves undertaking a high-carbohydrate diet and, during severe attacks, a glucose 10% infusion. It is estimated that AIP affects 5.9 per 1 000 000 people.

Acute intermittent porphyria (AIP), also called Swedish porphyria, is a rare inborn error of metabolism (IEM) and autosomal dominant disorder of heme biosynthesis caused by a defective HMBS gene. The HMBS gene codes for the protein hydroxymethylbilane synthase (porphobilinogen deaminase) which catalyzes the synthesis of porphobilinogen into hydroxymethylbilane. This disorder is characterized by a large accumulation of 5-aminolevulinic acid or porphobilinogen in both urine and serum. Most patients are asymptomatic between attacks. Symptoms of the disorder include abdominal pain, constipation, vomiting, hypertension, muscle weakness, seizures, delirium, coma, and depression. Treatment involves undertaking a high-carbohydrate diet and, during severe attacks, a glucose 10% infusion. It is estimated that AIP affects 5.9 per 1 000 000 people.

Acyclovir is a guanosine analog used to treat herpes simplex, varicella zoster, herpes zoster, herpes labialis, and acute herpetic keratitis. Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase.5 Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase.1 Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate inhibits the activity of DNA polymerase by competing with its substrate dGTP. Acyclovir triphosphate also gets incorporated into viral DNA, but since it lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, this causes DNA chain termination, preventing the growth of viral DNA. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.

(10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoylcarnitine 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, (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoic 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 (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoyl-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, (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoyl-CoA reacts with L-carnitine to form (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoylcarnitine 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, (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoyl-CoA and L-carnitine. (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoyl-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 (10E)-11-(3,4-dimethyl-5-pentylfuran-2-yl)undec-10-enoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

(10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoylcarnitine 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, (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoic 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 (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoyl-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, (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoyl-CoA reacts with L-carnitine to form (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoylcarnitine 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, (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoyl-CoA and L-carnitine. (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoyl-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 (10E)-11-(3,4-dimethyl-5-propylfuran-2-yl)undec-10-enoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

(10E)-8-Hydroxydodec-10-enoylcarnitine 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, (10E)-8-hydroxydodec-10-enoic 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 (10E)-8-hydroxydodec-10-enoyl-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, (10E)-8-hydroxydodec-10-enoyl-CoA reacts with L-carnitine to form (10E)-8-hydroxydodec-10-enoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (10E)-8-hydroxydodec-10-enoylcarnitine 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, (10E)-8-hydroxydodec-10-enoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (10E)-8-hydroxydodec-10-enoyl-CoA and L-carnitine. (10E)-8-Hydroxydodec-10-enoyl-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 (10E)-8-hydroxydodec-10-enoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

(10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoylcarnitine 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, (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoic 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 (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoyl-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, (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoyl-CoA reacts with L-carnitine to form (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoylcarnitine 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, (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoyl-CoA and L-carnitine. (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoyl-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 (10E,12E,14E)-16-hydroxy-9-oxooctadeca-10,12,14-trienoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.

(10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoylcarnitine 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, (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoic 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 (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoyl-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, (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoyl-CoA reacts with L-carnitine to form (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoylcarnitine 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, (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoyl-CoA and L-carnitine. (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoyl-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 (10E,12E,14E)-9-hydroxy-16-oxooctadeca-10,12,14-trienoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.