Pathways

Anidulafungin is a semi-synthetic echinocandin antifungal used in the treatment of several types of candida infections. It is known by the brand names Ecalta or Eraxis. It is a treatment for the fungal infections Candidemia and other forms of Candida infections (intra-abdominal abscess, and peritonitis), Aspergillus infections, and esophageal candidiasis. Also considered an alternative treatment for oropharyngeal canaidiasis.Anidulafungin is commonly used to treat fungal infections in the bloodstream, esophageal candidiasis, fungal peritonitis caused by Candida, intraabdominal abscesses, invasive aspergillosis, and oropharyngeal candidiasis. As an echinocandin antifungal, Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This prevents the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, which ultimately leads to osmotic instability and cell death.

Candicidin is a polyene antifungal antibiotic produced by a strain of Streptomyces griseus. It is especially effective against Candida albicans (more effective than amphotericin B), and is administered intravaginally in the treatment of vulvovaginal candidiasis. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of Candicidin. Candicidin binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Caspofungin is an echinocandin antifungal drug used to treat a variety of fungal infections. It is known as the brand Cancidas. It is used for the treatment of esophageal candidiasis and invasive aspergillosis in patients who are refractory to or intolerant of other therapies.It works by inhibiting cell wall synthesis. Caspofungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This prevents the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, which ultimately leads to osmotic instability and cell death.

Ibrexafungerp, also known as SCY-078 or MK-3118, or as the brand name Brexafemme, is a triterpene antifungal indicated in the treatment of vulvovaginal candidiasis and prevention of recurrent vulvovaginal candidiasis in post-menarchal patients. It is a derivative of enfumafungin and was developed out of a need to treat fungal infections that may have become resistant to echinocandins or azole antifungals. Ibrexafungerp is orally bioavailable compared to the echinocandins caspofungin, micafungin, and anidulafungin; which can only be administered parenterally. Similarly to echinocandin antifungals, Ibrexafungerp inhibits β-1,3-glucan synthase. While echinocandins bind to the FKS1 domain of β-1,3-glucan synthase, enfumafungin and its derivatives bind at an alternate site which allows them to maintain their activity against fungal infections that are resistant to echinocandins. The inhibition of β-1,3-glucan synthase prevents the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, which ultimately leads to osmotic instability and cell death.

The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. The latter compound reacts with hydrogen ion, NADPH through a squalene synthetase resulting in the release NADP, pyrophosphate and squalene. The latter compound reacts with hydrogen ion NADPH and oxygen through squalene monooxygenase resulting in the release of NADP, Water and (3S)-2,3-epoxy-2,3-dihydrosqualene. The latter compound reacts through a 2,3-oxidosqualene lanosterol cyclase resulting in the release of lanosterol. Lanosterol reacts with hydrogen ion, NADPH, and oxygen through a cytochrome P450 lanosterol 14a demethylase resulting in the release of formate, water, NADP and 14-demethyllanosterol. The latter compound reacts with hydrogen ion and NADPH through a c-14 sterol reductase resulting in the release of NADP and 4,4-dimethylzymosterol. The latter compound reacts with methylsterol monooxygenase resulting in the release of 4α-hydroxymethyl-4β-methyl-5α-cholesta-8,24-dien-3β-ol which reacts with methylsterol monooxygenase twice to obtain 4α-carboxy-4β-methyl-5α-cholesta-8,24-dien-3β-ol. The latter compound then reacts with an NADP C-3 sterol dehydrogenase resulting in the release of water, NADP and 3-dehydro-4-methylzymosterol. The latter compound then reacts with NADPH and a hydrogen ion through a 3-keto sterol reductase resulting in the release of NADP and 4alpha-methyl-zymosterol. The latter compound then reacts with a methylsterol monooxygenase 3 times, followed by one reaction with c-sterol dehydrogenase and one reaction with 3-keto sterol reductase resulting in the release of a zymosterol. The latter compound reacts with SAM through a sterol methyltransferase resulting in the release of s-adenosylhomocysteine and fecosterol. Fecosterol is isomerized into episterol. The latter compound reacts with c-5 sterol desaturase resulting in the release of ergosta-5,7,24(28)-trien-3β-ol which then reacts with a c-22 sterol desaturase resulting in the release of ergosta-5,7,22,24(28)-tetraen-3-β-ol. This latter compound then reacts with a C-24 sterol reductase resulting in the release of an ergosterol.

Griseofulvin is an antifungal agent used to treat ringworm infections of the skin, hair, and nails, namely: tinea corporis, tinea pedis, tinea cruris, tinea barbae, cradle cap or other conditions caused by Trichophyton or Microsporum fungi. Griseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells. It also has a greater affinity for diseased tissue. It binds to the new keratin which becomes resistant to fungal invasion. The exact mechanism by which Griseofulvin inhibits fungal cell growth is not clear, but it is thought to inhibit fungal cell mitosis and nuclear acid synthesis. At the action site, it binds to fungal tubulin at the beta site. This alters the fungal process of mitosis, likely inhibiting mytosis and preventing further growth of fungal cells.

Tavaborole is an antifungal agent used to treat onychomycosis, a fungal infection of the nail and nail bed due to Trichophyton rubrum or Trichophyton mentagrophytes infection. Tavaborole functions by inhibiting Leucyl-tRNA synthetase, or LeuRS, an essential fungal enzyme required for protein synthesis and for the catalysis of ATP-dependent ligation of L-leucine to tRNA(Leu). This blocks the protein synthesis in the fungal cell which leads to cell degradation and death.

Albendazole is a broad-spectrum benzimidazole anthelmintic used to treat parenchymal neurocysticercosis and other helminth infections. Albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by diminishing its energy production, ultimately leading to immobilization and death of the parasite. It works by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. As cytoplasmic microtubules are critical in promoting glucose uptake in larval and adult stages of the susceptible parasites, the glycogen stores of the parasites are depleted. Cellular glucose dissipates which results in decreased production and dissipation of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes also result in decreased production of adenosine triphosphate (ATP),

Oritavancin is an antibacterial agent used to treat acute bacterial skin and skin structure infections caused by susceptible gram-positive bacteria. Oritavancin is indicated for the treatment of adult patients with acute bacterial skin and skin structure (including subcutaneous) infection. It is used for confirmed/suspected infections with designated and susceptible gram-positive organisms. The cell wall is vital for the survival and replication of bacteria, making it a primary target for antibiotic therapy. Oritavancin works against susceptible gram-positive organisms via three separate mechanisms. It binds to the stem peptide of peptidoglycan precursors, inhibiting transglycosylation (polymerization). This process normally occurs during cell wall synthesis. Secondly, oritavancin inhibits crosslinking during bacterial cell wall biosynthesis via binding to cell wall pentaglycyl peptide bridging segments. Finally, this drug also acts by disrupting the bacterial cell membrane, interfering with its integrity, which eventually leads to cell death by various mechanisms.

Glycolysis is a metabolic pathway with sequence of ten reactions involving ten intermediate compounds that converts glucose to pyruvate. Glycolysis release free energy for forming high energy compound such as ATP and NADH. Glycolysis is consisted of two phases, which one of them is chemical priming phase and second phase is energy-yielding phase. As the starting compound of chemical priming phase, D-glucose can be obtained from galactose metabolism or imported by monosaccharide-sensing protein 1 from outside of cell. D-Glucose is catalyzed by probable hexokinase-like 2 protein to form glucose 6-phosphate which is powered by ATP. Glucose 6-phosphate transformed to fructose 6-phosphate by glucose-6-phosphate isomerase, which the later compound will be converted to fructose 1,6-bisphosphate, which is the last reaction of chemical priming phase by 6-phosphofructokinase with cofactor magnesium, and it is also powered by ATP. Before entering the second phase, aldolase catalyzing the hydrolysis of F1,6BP into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate and glyceraldehyde 3-phosphate can convert to each other bidirectionally by facilitation of triosephosphate isomerase. The second phase of glycolysis is yielding-energy phase that produce ATP and NADH. At the first step, D-glyceraldehyde 3-phosphate is catalyzed to glyceric acid 1,3-biphosphate by glyceraldehyde-3-phosphate dehydrogenase with NAD, which also generate NADH. ATP is generated through the reaction that convert glyceric acid 1,3-biphosphate to 3-phosphoglyceric acid. Phosphoglycerate mutase 2 catalyze 3-phosphoglyceric acid to 2-Phospho-D-glyceric acid, and alpha-enolase with cofactor magnesium catalyzes 2-Phospho-D-glyceric acid to phosphoenolpyruvic acid. Eventually, plastidial pyruvate kinase 4 converts phosphoenolpyruvic acid to pyruvate with cofactor magnesium and potassium and ADP. Pyruvate will undergo pyruvate metabolism, tyrosine metabolism and pantothenate and CoA biosynthesis.