Browsing Pathways

As is commonly known there are many vitamins, the vitamin B complex group being one of the most well known. An important vitamin B complex group vitamin is vitamin B6, which is water-soluble. Moreover, this vitamin comes in various forms, one of which is an active form, known by the name pyridoxal phosphate or PLP. PLP serves as cofactor in a variety of reactions including from amino acid metabolism, (in particular in reactions such as transamination, deamination, and decarboxylation). To complicate matters however, there are in fact seven alternate forms of this same vitamin. These include pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), 4-pyridoxic acid (PA), and the aforementioned pyridoxal 5’-phosphate (PLP). One of these forms, PA, is in fact a catabolite whose presence is found in excreted urine. For a person to absorb some of these active forms of vitamin B6 such as PLP or PMP they must first be dephosphorylized. This done via an alkaline enzyme phosphatase. There are a wide variety of biproducts from the metabolism in question, most of which find there ways into the urine and from there are excreted. One such biproduct is 4-pyridoxic acid. In fact this last biproduct is found in such large quantities that estimates of vitamin B6 metabolism birproducts show that 4-pyridoxic acid is as much as 40-60% of all the biproducts.Of course, it is not the only product of metabolism. Others include,include pyridoxal, pyridoxamine, and pyridoxine.

As is commonly known there are many vitamins, the vitamin B complex group being one of the most well known. An important vitamin B complex group vitamin is vitamin B6, which is water-soluble. Moreover, this vitamin comes in various forms, one of which is an active form, known by the name pyridoxal phosphate or PLP. PLP serves as cofactor in a variety of reactions including from amino acid metabolism, (in particular in reactions such as transamination, deamination, and decarboxylation). To complicate matters however, there are in fact seven alternate forms of this same vitamin. These include pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), 4-pyridoxic acid (PA), and the aforementioned pyridoxal 5’-phosphate (PLP). One of these forms, PA, is in fact a catabolite whose presence is found in excreted urine. For a person to absorb some of these active forms of vitamin B6 such as PLP or PMP they must first be dephosphorylized. This done via an alkaline enzyme phosphatase. There are a wide variety of biproducts from the metabolism in question, most of which find there ways into the urine and from there are excreted. One such biproduct is 4-pyridoxic acid. In fact this last biproduct is found in such large quantities that estimates of vitamin B6 metabolism birproducts show that 4-pyridoxic acid is as much as 40-60% of all the biproducts.Of course, it is not the only product of metabolism. Others include,include pyridoxal, pyridoxamine, and pyridoxine.

As is commonly known there are many vitamins, the vitamin B complex group being one of the most well known. An important vitamin B complex group vitamin is vitamin B6, which is water-soluble. Moreover, this vitamin comes in various forms, one of which is an active form, known by the name pyridoxal phosphate or PLP. PLP serves as cofactor in a variety of reactions including from amino acid metabolism, (in particular in reactions such as transamination, deamination, and decarboxylation). To complicate matters however, there are in fact seven alternate forms of this same vitamin. These include pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), 4-pyridoxic acid (PA), and the aforementioned pyridoxal 5’-phosphate (PLP). One of these forms, PA, is in fact a catabolite whose presence is found in excreted urine. For a person to absorb some of these active forms of vitamin B6 such as PLP or PMP they must first be dephosphorylized. This done via an alkaline enzyme phosphatase. There are a wide variety of biproducts from the metabolism in question, most of which find there ways into the urine and from there are excreted. One such biproduct is 4-pyridoxic acid. In fact this last biproduct is found in such large quantities that estimates of vitamin B6 metabolism birproducts show that 4-pyridoxic acid is as much as 40-60% of all the biproducts.Of course, it is not the only product of metabolism. Others include,include pyridoxal, pyridoxamine, and pyridoxine.

As is commonly known there are many vitamins, the vitamin B complex group being one of the most well known. An important vitamin B complex group vitamin is vitamin B6, which is water-soluble. Moreover, this vitamin comes in various forms, one of which is an active form, known by the name pyridoxal phosphate or PLP. PLP serves as cofactor in a variety of reactions including from amino acid metabolism, (in particular in reactions such as transamination, deamination, and decarboxylation). To complicate matters however, there are in fact seven alternate forms of this same vitamin. These include pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), 4-pyridoxic acid (PA), and the aforementioned pyridoxal 5’-phosphate (PLP). One of these forms, PA, is in fact a catabolite whose presence is found in excreted urine. For a person to absorb some of these active forms of vitamin B6 such as PLP or PMP they must first be dephosphorylized. This done via an alkaline enzyme phosphatase. There are a wide variety of biproducts from the metabolism in question, most of which find there ways into the urine and from there are excreted. One such biproduct is 4-pyridoxic acid. In fact this last biproduct is found in such large quantities that estimates of vitamin B6 metabolism birproducts show that 4-pyridoxic acid is as much as 40-60% of all the biproducts.Of course, it is not the only product of metabolism. Others include,include pyridoxal, pyridoxamine, and pyridoxine.

Vitamin B6 belongs to the vitamin B complex group and is water-soluble. The active form is Pyridoxal phosphate (PLP) which acts as a cofactor for various essential enzymes in reactions including: amino acid metabolism, transamination, deamination, and decarboxylation. Other forms of the vitamin include: pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), and 4-pyridoxic acid (PA). Most animals are unable to synthesize the vitamin while most bacteria are able too. Some organisms also import the vitamin to supplement or augment biosynthesis. S. cerevisiae has transporter Tpn1p on the plasma membrane to import vitamin B6. It transports mostly PN, a precursor of PLP, but also PM and PL. Vitamin B6 is also an antioxidant to provide protection against reactive oxygen species. It has been shown that vitamin B6 synthesis is increased in response to cell stress.

The biosynthesis of thiamine begins with pyrithiamine reacting with thiaminase 2 resulting in the release of 4-Amino-5-hydroxymethyl-2-methylpyrimidine. The latter compound reacts with a hydroxymethylpyrimidine/phosphomethylpyrimidine kinase resulting in the release of 4-amino-2-methyl-5-phosphomethylpyrimidine. The latter compound reacts with a hydroxymethylpyrimidine/phosphomethylpyrimidine kinase resulting in the release of 2-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate. The latter compound reacts with 4-methyl-5-(2-phosphonooxyethyl)thiazole, a product of oxythiamine metabolism, through a Thiamine biosynthetic bifunctional enzyme resultin in the release of a Thiamine monophosphate. The latter compound is phosphatased through a acid phosphatase complex resulting in the release of thiamine. The latter compound is phosphorylated through a thiamin pyrophosphokinase resulting in the release of thiamine pyrophosphate.

Vitamin A deficiency can be caused by many causes. A defect in the BCMO1 gene which codes for beta,beta-carotene 15,15’-monooxygenase is one of them. Beta,beta-carotene 15,15’-monooxygenase catalyzes the chemical reaction where the two substrates are beta-carotene and O2, whereas its product is retinal. A defect in this enzyme results in decrease of levels of retinal and vitamin A in serum; Signs and symptoms include night blindness, poor adaptation to darkness, dry skin and hair.

Vitamin A deficiency can be caused by many causes. A defect in the BCMO1 gene which codes for beta,beta-carotene 15,15’-monooxygenase is one of them. Beta,beta-carotene 15,15’-monooxygenase catalyzes the chemical reaction where the two substrates are beta-carotene and O2, whereas its product is retinal. A defect in this enzyme results in decrease of levels of retinal and vitamin A in serum; Signs and symptoms include night blindness, poor adaptation to darkness, dry skin and hair.

Vitamin A deficiency can be caused by many causes. A defect in the BCMO1 gene which codes for beta,beta-carotene 15,15’-monooxygenase is one of them. Beta,beta-carotene 15,15’-monooxygenase catalyzes the chemical reaction where the two substrates are beta-carotene and O2, whereas its product is retinal. A defect in this enzyme results in decrease of levels of retinal and vitamin A in serum; Signs and symptoms include night blindness, poor adaptation to darkness, dry skin and hair.

Vinorelbine (also named Navelbine) is a semisynthetic vinca alkaloid. Vinorelbine are used as chemotherapy medication such as an antimitotic anticancer agent. The mechanism of vinorelbine is the inhibition of microtubule dynamics that would cause mitotic arrest and eventual cell death. As a microtubule destabilizing agent, vinorelbine stimulates mitotic spindle destruction and microtubule depolymerization at high concentrations. At lower clinically relevant concentrations, vinorelbine can block mitotic progression. Unlike the taxanes, which bind poorly to soluble tubulin, vinorelbine can bind both soluble and microtubule-associated tubulin. To be able stabilizing the kinetics of microtule, vinorelbine rapidly and reversibly bind to soluble tubulin which can increase the affinity of tublin by the induction of conformational changes of tubulin. Vinorelbine binds to β-tubulin subunits at the positive end of microtubules at a region called the _Vinca_-binding domain. Binding between vinorelbine and solubale tubulin decreases the rate of microtubule dynamics (lengthening and shortening) and increases the duration of attenuated state of microtubules. Therefore, the proper assembly of the mitotic spindle could be prevented; and the tension at the kinetochores of the chromosomes could be reduced. Subsequently, chromosomes can not progress to the spindle equator at the spindle poles. Progression from metaphase to anaphase is blocked and cells enter a state of mitotic arrest. The cells may then undergo one of several fates. The tetraploid cell may undergo unequal cell division producing aneuploid daughter cells. Alternatively, it may exit the cell cycle without undergoing cell division, a process termed mitotic slippage or adaptation. These cells may continue progressing through the cell cycle as tetraploid cells (Adaptation I), may exit G1 phase and undergo apoptosis or senescence (Adaption II), or may escape to G1 and undergo apoptosis during interphase (Adaptation III). Another possibility is cell death during mitotic arrest. Alternatively, mitotic catastrophe may occur and cause cell death. Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. Phosphorylation of Bcl-2 subsequently inhibits the formation Bcl-2-BAX heterodimers. This results in decreased anti-apoptotic activity. One way in which cells have developed resistance against the vinca alkaloids is by drug efflux. Drug efflux is mediated by a number of multidrug resistant transporters as depicted in this pathway.