Pathways

E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate which is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate. 3-Dehydro-L-gulonate is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can then be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate, which is then changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. The product also changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate, which is finally used as part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate, which is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. The product again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. Xylulose 5-phosphate then continues as part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.

E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate which is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate. 3-Dehydro-L-gulonate is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can then be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate, which is then changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. The product also changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate, which is finally used as part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate, which is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. The product again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. Xylulose 5-phosphate then continues as part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.

E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate which is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate. 3-Dehydro-L-gulonate is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can then be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate, which is then changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. The product also changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate, which is finally used as part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate, which is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. The product again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. Xylulose 5-phosphate then continues as part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.

E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate which is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate. 3-Dehydro-L-gulonate is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can then be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate, which is then changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. The product also changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate, which is finally used as part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate, which is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. The product again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. Xylulose 5-phosphate then continues as part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.

E. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions. Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate which is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate. 3-Dehydro-L-gulonate is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate. L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate. The compound 3-keto-L-gulonate 6-phosphate can then be processed aerobically or anaerobically. Aerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate, which is then changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. The product also changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate, which is finally used as part of the pentose phosphate pathway. Anaerobic: 3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate, which is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. The product again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. Xylulose 5-phosphate then continues as part of the pentose phosphate pathway. Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP. Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.

L-Ascorbate commonly known as vitamin C is a reducing agent and cofactor in reactions catalyzed by copper-dependent monooxygenases and iron-dependent dioxygenases. It is synthesized from direct hydrolysis of UDP-α-D-glucuronate by enzymes bound to the endoplasmic reticulum membrane. It can be biosynthesized in many plants and bacteria and used as vitamin supplements. Other common uses include being an additive for beverage production and live stock feed. Without sufficient levels of L-ascorbate disorders such as scurvy may develop.

Asciminib is an inhibitor of ABL/BCR-ABL1 tyrosine kinase for the treatment of patients with Philadelphia chromosome-positive CML, including those with the T315I mutation. Asciminib is an allosteric inhibitor of the BCR-ABL1 tyrosine kinase. It binds to the myristoyl pocket of the ABL1 portion of the fusion protein and locks it into an inactive conformation, preventing its oncogenic activity. Asciminib exerts its therapeutic activity by inhibiting an oncogenic protein responsible for the proliferation of CML. It may be administered orally once or twice a day depending on the condition being treated. By increasing the total daily dose 5-fold as compared to standard therapy (80mg daily vs. 400mg daily), it can be used to treat Ph+ CML with the T315I mutation, a typically treatment-resistant variant of the disease.

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