Pathways

Zoledronate (also named zoledronic acid, Zometa or Reclast) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Zoledronate targets farnesyl pyrophosphate (FPP) synthase by inhibiting the function of this enzyme in the mevalonate pathway, which prevent the biosynthesis of Geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are important for geranylgeranylation and farnesylation of GTPase signalling proteins. Lack of Geranyl-PP and farnesyl pyrophosphate will result in decreased rate of bond resorption and turnover as well as block the osteoclast activity, which lead to an increasing mass gain in bone (i.e. net gain in bone mass).

Zoledronic acid, or CGP 42'446,8 is a third generation, nitrogen containing bisphosphonate similar to ibandronic acid, minodronic acid, and risedronic acid. Zoledronic acid is used to treat and prevent multiple forms of osteoporosis, hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, and Paget’s disease of bone.Zoledronic acid was first described in the literature in 1994. Zoledronic acid is indicated to treat hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid induced osteoporosis, and Paget's disease of bone in men and women.Zoledronic acid is also indicated for the prevention of osteoporosis in post menopausal women and glucocorticoid induced osteoporosis Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as zoledronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. zoledronate also activated caspases which further contribute to apoptosis.

The discovery of AIDS prompted the search for agents that block the HIV replication process. Zidovudine (AZT) is a nucleoside analogue of thymidine, and was shown to reduce considerably the mortality of patients with AIDS. Zidovudine is toxic to the hemtopoietic system, causing anemia and neutropenia. It is clear, however, that disease progression can occur during continued administration of zidovudine. Moreover, zidovudine is not effective in treating Kaposi sarcoma, a common complication of HIV infection. Zidovudine therapy is also associated with a high incidence of toxicity, primarily bone marrow suppression, that requires dosage reduction or discontinuation of the therapy.

Zellweger syndrome, also known as cerebrohepatorenal syndrome, is an autosomal recessive peroxisome biogenesis disorder that is part of the family of Zellweger spectrum disorders. It is caused by a defect in one of 12 or more of the PEX genes (PEX1, 2, 3, 5, 6, 10, 12, 13, 14, 16, 19 and 26) that produce proteins called peroxins. Peroxins are used in the formation of peroxisomes, and can be involved in recognition of proteins targeted for the peroxisome, as well as their transport into the peroxisome. Peroxisomes typically break down both very long chain and branched fatty acids, but if they aren't present, these fatty acids build up in the blood and body, harming organs such as the brain and liver. Additionally, due to the fact that some processes, such as plasmalogen biosynthesis, occur in or using peroxisomes, and can lead to deficiencies in plasmalogens. These are important in brain and lung function, leading to other symptoms. Zellweger syndrome is characterized by an increase in levels of very long chain fatty acids in the blood plasma, as well as more visible physical symptoms, such as an abnormally large or small head at birth, characteristic facial features and poor muscle tone, which can lead to an inability of infants to feed. Other symptoms include an enlarged liver, skeletal abnormalities and low CNS function. Infants very rarely live longer than one year, and the only treatment is for symptoms the patient is experiencing, not for the syndrome itself.

Zellweger syndrome, also known as cerebrohepatorenal syndrome, is an autosomal recessive peroxisome biogenesis disorder that is part of the family of Zellweger spectrum disorders. It is caused by a defect in one of 12 or more of the PEX genes (PEX1, 2, 3, 5, 6, 10, 12, 13, 14, 16, 19 and 26) that produce proteins called peroxins. Peroxins are used in the formation of peroxisomes, and can be involved in recognition of proteins targeted for the peroxisome, as well as their transport into the peroxisome. Peroxisomes typically break down both very long chain and branched fatty acids, but if they aren't present, these fatty acids build up in the blood and body, harming organs such as the brain and liver. Additionally, due to the fact that some processes, such as plasmalogen biosynthesis, occur in or using peroxisomes, and can lead to deficiencies in plasmalogens. These are important in brain and lung function, leading to other symptoms. Zellweger syndrome is characterized by an increase in levels of very long chain fatty acids in the blood plasma, as well as more visible physical symptoms, such as an abnormally large or small head at birth, characteristic facial features and poor muscle tone, which can lead to an inability of infants to feed. Other symptoms include an enlarged liver, skeletal abnormalities and low CNS function. Infants very rarely live longer than one year, and the only treatment is for symptoms the patient is experiencing, not for the syndrome itself.

Zellweger syndrome, also known as cerebrohepatorenal syndrome, is an autosomal recessive peroxisome biogenesis disorder that is part of the family of Zellweger spectrum disorders. It is caused by a defect in one of 12 or more of the PEX genes (PEX1, 2, 3, 5, 6, 10, 12, 13, 14, 16, 19 and 26) that produce proteins called peroxins. Peroxins are used in the formation of peroxisomes, and can be involved in recognition of proteins targeted for the peroxisome, as well as their transport into the peroxisome. Peroxisomes typically break down both very long chain and branched fatty acids, but if they aren't present, these fatty acids build up in the blood and body, harming organs such as the brain and liver. Additionally, due to the fact that some processes, such as plasmalogen biosynthesis, occur in or using peroxisomes, and can lead to deficiencies in plasmalogens. These are important in brain and lung function, leading to other symptoms. Zellweger syndrome is characterized by an increase in levels of very long chain fatty acids in the blood plasma, as well as more visible physical symptoms, such as an abnormally large or small head at birth, characteristic facial features and poor muscle tone, which can lead to an inability of infants to feed. Other symptoms include an enlarged liver, skeletal abnormalities and low CNS function. Infants very rarely live longer than one year, and the only treatment is for symptoms the patient is experiencing, not for the syndrome itself.

Zeaxanthin biosynthesis is a pathway that occurs in the chloroplast by which lycopene becomes zeaxanthin, one of the most common carotenoid alcohols found in nature . The first two reactions are catalyzed by lycopene beta cyclase which uses NAD(P)H as a cofactor to convert lycopene into gamma-carotene and gamma-carotene into beta-carotene. The last two reactions are catalyzed by beta-carotene 3-hydroxylase which uses ferredoxin and Fe2+ as cofactors to convert beta-carotene into beta-cryptoxanthin and beta-cryptoxanthin into zeaxanthin.

Zeatin encourages lateral bud growth, resulting in bushier plants. It stimulates cell division when sprayed on meristems. Terpenoid backbone biosynthesis produces dimethylallyl diphosphate which, with different reactants, can result in different products with a byproduct of diphosphate. When reacted with tRNA adenine via tRNA dimethylallyltransferase, it results in the formation of tRNA containing 6-isopentenyl adenosine. When reacted via adenylate isopentenyltransferase 1, chloroplastic with either ATP, ADP, or AMP, it results in the formation of the corresponding isopentenyl, which in turn reacts with oxygen and reduced NADPH hemoprotein reductase via cytokinin hydroxylase, resulting in the formation of trans-zeatin riboside with the corresponding phosphates and byproducts of water and oxidized NADPH hemoprotein reductase.

Zalcitabine (ddc) is a dideoxynucleoside antiretroviral drug that when used in combination with zidovudine improves the viral load and CD4+ cell count of patients infected with Human Immunodeficiency Virus Type 1 (HIV-1). Zalcitabine is phosphorylated to it’s active form metabolite 2′,3′-dideoxycytidine 5′-triphosphate (ddCTP) in both healthy and infected cells. ddCTP competes with deoxycytidine triphosphate inhibiting the enzyme reverse transcriptase from using the substrates to elongate the viral DNA strand ultimately halting HIV replication.