Pathways

Amylase enzymes secreted in saliva by the parotid gland and in the small intestine play an important role in initiating starch digestion. The products of starch digestion are but not limited to maltotriose, maltose, limit dextrin, and glucose. The action of enterocytes of the small intestine microvilli further break down limit dextrins and disaccharides into monosaccharides: glucose, galactose, and fructose. Once released from starch or once ingested, sucrose can be degraded into beta-D-fructose and alpha-D-glucose via lysosomal alpha-glucosidase or sucrose-isomaltase. Beta-D-fructose can be converted to beta-D-fructose-6-phosphate by glucokinase and then to alpha-D-glucose-6-phosphate by the action of glucose phosphate isomerase. Phosphoglucomutase 1 can then act on alpha-D-glucose-6-phosphate (G6P) to generate alpha-D-glucose-1-phosphate. Alpha-D-glucose-1-phosphate (G6P) has several possible fates. It can enter into gluconeogenesis, glycolysis or the nucleotide sugar metabolism pathway. UDP-glucose pyrophosphorylase 2 can convert alpha-D-glucose-1-phosphate into UDP-glucose, which can then be converted to UDP-xylose or UDP-glucuronate and, eventually to glucuronate. UDP-glucose can also serve as a precursor to the synthesis of glycogen via glycogen synthase. Glycogen is an analogue of amylopectin (“plant starch”) and acts as a secondary short-term energy storage for animal cells. It’s formed primarily in liver and muscle tissues, but is also formed at secondary sites such as the central nervous system and the stomach. In both cases it exists as free granules in the cytosol. Glycogen is a crucial element of the glucose cycle as another enzyme, glycogen phosphorylase, cleaves off glycogen from the nonreducing ends of a chain to producer glucose-1-phosphate monomers. From there, the glucose-1-phosphate monomers have three possible fates: (1) enter the glycolysis pathway as glucose-6—phosphate (G6P) to generate energy, (2) enter the pentose phosphate pathway to produce NADPH and pentose sugar, or (3) enter the gluconeogenesis pathway by being dephosphorylated into glucose in liver or kidney tissues. To initiate the process of glycogen chain-lengthening, glycogenin is required because glycogen synthase can only add to existing chains. This action is subsequently followed by the action of glycogen synthase which catalyzes the formation of polymers of UDP-glucose connected by (α1→4) glycosidic bonds to form a glycogen chain. Importantly, amylo (α1→4) to (α1→6) transglycosylase catalyzes glycogen branch formation via the transfer of 6-7 glucose residues from a nonreducing end with greater than 11 residues to the C-6 OH- group in the interior of a glycogen molecule.

The metabolism of starch and sucrose begins with D-fructose interacting with a D-glucose in a reversible reaction through a maltodextrin glucosidase resulting in a water molecule and a sucrose. D-fructose is phosphorylated through an ATP driven fructokinase resulting in the release of an ADP, a hydrogen ion and a Beta-D-fructofuranose 6-phosphate. This compound can also be introduced into the cytoplasm through either a mannose PTS permease or a hexose-6-phosphate:phosphate antiporter. The Beta-D-fructofuranose 6-phosphate is isomerized through a phosphoglucose isomerase resulting in a Beta-D-glucose 6-phosphate. This compound can also be incorporated by glucose PTS permease or a hexose-6-phosphate:phosphate antiporter. The beta-D-glucose 6 phosphate can also be produced by a D-glucose being phosphorylated by an ATP-driven glucokinase resulting in a ADP, a hydrogen ion and a Beta-D-glucose 6 phosphate. The beta-D-glucose can produce alpha-D-glucose-1-phosphate by two methods: 1.-Beta-D-glucose is isomerized into an alpha-D-Glucose 6-phosphate and then interacts in a reversible reaction through a phosphoglucomutase-1 resulting in a alpha-D-glucose-1-phosphate. 2.-Beta-D-glucose interacts with a putative beta-phosphoglucomutase resulting in a Beta-D-glucose 1-phosphate. Beta-D-glucose 1-phosphate can be incorporated into the cytoplasm through a glucose PTS permease. This compound is then isomerized into a Alpha-D-glucose-1-phosphate The beta-D-glucose can cycle back into a D-fructose by first interacting with D-fructose in a reversible reaction through a Polypeptide: predicted glucosyltransferase resulting in the release of a phosphate and a sucrose. The sucrose then interacts in a reversible reaction with a water molecule through a maltodextrin glucosidase resulting in a D-glucose and a D-fructose. Alpha-D-glucose-1-phosphate can produce glycogen in by two different sets of reactions: 1.-Alpha-D-glucose-1-phosphate interacts with a hydrogen ion and an ATP through a glucose-1-phosphate adenylyltransferase resulting in a pyrophosphate and an ADP-glucose. The ADP-glucose then interacts with an amylose through a glycogen synthase resulting in the release of an ADP and an Amylose. The amylose then interacts with 1,4-α-glucan branching enzyme resulting in glycogen 2.- Alpha-D-glucose-1-phosphate interacts with amylose through a maltodextrin phosphorylase resulting in a phosphate and a glycogen. Alpha-D-glucose-1-phosphate can also interacts with UDP-galactose through a galactose-1-phosphate uridylyltransferase resulting in a galactose 1-phosphate and a Uridine diphosphate glucose. The UDP-glucose then interacts with an alpha-D-glucose 6-phosphate through a trehalose-6-phosphate synthase resulting in a uridine 5'-diphosphate, a hydrogen ion and a Trehalose 6- phosphate. The latter compound can also be incorporated into the cytoplasm through a trehalose PTS permease. Trehalose interacts with a water molecule through a trehalose-6-phosphate phosphatase resulting in the release of a phosphate and an alpha,alpha-trehalose.The alpha,alpha-trehalose can also be obtained from glycogen being metabolized through a glycogen debranching enzyme resulting in a the alpha, alpha-trehalose. This compound ca then be hydrated through a cytoplasmic trehalase resulting in the release of an alpha-D-glucose and a beta-d-glucose. Alpha-D-glucose-1-phosphate can be metabolized to produce dTDP-Beta-L-rhamnose. This happens by Alpha-D-glucose-1-phosphate reacting with a dTTP and a hydrogen ion through a dTDP-glucose pyrophosphorylase resulting in the release of a pyrophosphate and a dTDP-alpha-D-glucose. This coumpound in turn reacts with a dTDP-glucose 4,6-dehydratase resulting in the release of a water molecule and a dTDP-4-dehydro-6-deoxy-alpha-D-glucopyranose. The latter compound reacts with a dTDP-4-dehydrorhamnose 3,5-epimerase resulting in the release of a dTDP-4-dehydro-beta-L-rhamnose. This compound in turn gets metabolized by a NADPH dependent dTDP-4-dehydrorhamnose reductase resulting in a release of a NADP and a dTDP-beta-L-rhamnose Glycogen is then metabolized by reacting with a phosphate through a glycogen phosphorylase resulting in a alpha-D-glucose-1-phosphate and a dextrin. The dextrin is then hydrated through a glycogen phosphorylase-limit dextrin α-1,6-glucohydrolase resulting in the release of a debranched limit dextrin and a maltotetraose. This compound can also be incorporated into the cytoplasm through a maltose ABC transporter. The maltotetraose interacts with a phosphate through a maltodextrin phosphorylase releasing a alpha-D-glucose-1-phosphate and a maltotriose. The maltotriose can also be incorporated through a maltose ABC transporter. The maltotriose can then interact with water through a maltodextrin glucosidase resulting in a D-glucose and a D-maltose. D-maltose can also be incorporated through a maltose ABC transporter The D-maltose can then interact with a maltotriose through a amylomaltase resulting in a maltotetraose and a D-glucose. The D-glucose is then phosphorylated through an ATP driven glucokinase resulting in a hydrogen ion, an ADP and a Beta-D-glucose 6-phosphate

The cellulase enzyme system consists of cellobiohydrolase, endoglucanase, and beta-glucosidase and has been extensively studied with respect to its biosynthesis, properties, mode of action, application, and, most recently, secretion mechanisms. A knowledge of the factors governing the biosynthesis and secretion of these enzymes at the molecular level will be useful in maximizing enzyme productivity in extracellular fluid.

Sucrose is common natural plant produced disaccharide composed of one glucose and one fructose, its molecular formula is C12H22O11. Starch is a Homo-polymeric carbohydrate composed of glucose units joined by glycosidic bonds. it is used as energy storage and converted for use when glucagon stimulates PKA for increase in gluconeogenesis activity, therefore increase the conversion of glycogen to glucose units. Glucose 1 phosphate is a intermediate of this pathway, it can be converted to Glucose 6 phosphate for glycolysis use when stimulated by Insulin. These sugars can also go enter nucleotide and amino acid synthesis pathways through transamination reactions

Amylase enzymes secreted in saliva by the parotid gland and in the small intestine play an important role in initiating starch digestion. The products of starch digestion are but not limited to maltotriose, maltose, limit dextrin, and glucose. The action of enterocytes of the small intestine microvilli further break down limit dextrins and disaccharides into monosaccharides: glucose, galactose, and fructose. Once released from starch or once ingested, sucrose can be degraded into beta-D-fructose and alpha-D-glucose via lysosomal alpha-glucosidase or sucrose-isomaltase. Beta-D-fructose can be converted to beta-D-fructose-6-phosphate by glucokinase and then to alpha-D-glucose-6-phosphate by the action of glucose phosphate isomerase. Phosphoglucomutase 1 can then act on alpha-D-glucose-6-phosphate (G6P) to generate alpha-D-glucose-1-phosphate. Alpha-D-glucose-1-phosphate (G6P) has several possible fates. It can enter into gluconeogenesis, glycolysis or the nucleotide sugar metabolism pathway. UDP-glucose pyrophosphorylase 2 can convert alpha-D-glucose-1-phosphate into UDP-glucose, which can then be converted to UDP-xylose or UDP-glucuronate and, eventually to glucuronate. UDP-glucose can also serve as a precursor to the synthesis of glycogen via glycogen synthase. Glycogen is an analogue of amylopectin (“plant starch”) and acts as a secondary short-term energy storage for animal cells. It’s formed primarily in liver and muscle tissues, but is also formed at secondary sites such as the central nervous system and the stomach. In both cases it exists as free granules in the cytosol. Glycogen is a crucial element of the glucose cycle as another enzyme, glycogen phosphorylase, cleaves off glycogen from the nonreducing ends of a chain to producer glucose-1-phosphate monomers. From there, the glucose-1-phosphate monomers have three possible fates: (1) enter the glycolysis pathway as glucose-6—phosphate (G6P) to generate energy, (2) enter the pentose phosphate pathway to produce NADPH and pentose sugar, or (3) enter the gluconeogenesis pathway by being dephosphorylated into glucose in liver or kidney tissues. To initiate the process of glycogen chain-lengthening, glycogenin is required because glycogen synthase can only add to existing chains. This action is subsequently followed by the action of glycogen synthase which catalyzes the formation of polymers of UDP-glucose connected by (α1→4) glycosidic bonds to form a glycogen chain. Importantly, amylo (α1→4) to (α1→6) transglycosylase catalyzes glycogen branch formation via the transfer of 6-7 glucose residues from a nonreducing end with greater than 11 residues to the C-6 OH- group in the interior of a glycogen molecule.

Carbohydrates are a major component of the diet, and include starch (amylose and amylopectin) and disaccharides such as sucrose, lactose, maltose and, in small amounts, trehalose. Once released from starch or once ingested, sucrose can be degraded into beta-D-fructose and alpha-D-glucose via lysosomal alpha-glucosidase or sucrose-isomaltase. Beta-D-Fructose can be converted to beta-D-fructose-6-phosphate by glucokinase and then to alpha-D-glucose-6-phosphate by the action of glucose phosphate isomerase. Phosphoglucomutase 1 can then act on alpha-D-glucose-6-phosphate (G6P) to generate alpha-D-glucose-1-phosphate. alpha-D-Glucose-1-phosphate (G6P) has several possible fates. It can enter into gluconeogenesis, glycolysis, or the nucleotide sugar metabolism pathway. UDP-glucose pyrophosphorylase 2 can convert alpha-D-glucose-1-phosphate into UDP-glucose, UDP-glucose can then be used to produce D-glucose via trehalose. UDP-glucose can also serve as a precursor to the synthesis of glycogen via glycogen synthase. Glycogen is a starch analogue commonly called an animal starch. Glycogen is found in the cytosol in granules. Glycogen is cleaved and converted to glucose-6-phosphate (G6P) which undergoes glycolysis or can enter the pentose phosphate pathway.

The STAT3 signalling pathway is a pathway activated by many different cytokines. It has also been found to be activated by many carcinogens. Cytokines are small proteins. These proteins are released by some of the cells in the immune system, and are vital to signalling pathways in the body of mammals. STAT3 is very important in the activation of the expression of certain mediators in the liver. STAT3 binds at the phosphotyrosine receptor which in turn phosphorylates tyrosine 705 at the C-terminal domain of STAT3, activating STAT3. If a receptor is missing tyrosine-kinase activity it will find tyrosine-kinases that are associated to the receptor, including JAK and Src when it is time for ligand engagement. Thanks to this recruitment, STAT3 is phosphorylated through the tyrosine phosphorylation cascade. This means that STAT3 is now activated, and its compounds disconnect from the receptor site, and relocate to the nucleus. Once there, the compounds bind to DNA response elements, and take part in many processes against target genes, such as apoptosis and cell proliferation, regulating their transcription.

The STAT3 signalling pathway is a pathway activated by many different cytokines. It has also been found to be activated by many carcinogens. Cytokines are small proteins. These proteins are released by some of the cells in the immune system, and are vital to signalling pathways in the body of mammals. STAT3 is very important in the activation of the expression of certain mediators in the liver. STAT3 binds at the phosphotyrosine receptor which in turn phosphorylates tyrosine 705 at the C-terminal domain of STAT3, activating STAT3. If a receptor is missing tyrosine-kinase activity it will find tyrosine-kinases that are associated to the receptor, including JAK and Src when it is time for ligand engagement. Thanks to this recruitment, STAT3 is phosphorylated through the tyrosine phosphorylation cascade. This means that STAT3 is now activated, and its compounds disconnect from the receptor site, and relocate to the nucleus. Once there, the compounds bind to DNA response elements, and take part in many processes against target genes, such as apoptosis and cell proliferation, regulating their transcription.

The STAT3 signalling pathway is a pathway activated by many different cytokines. It has also been found to be activated by many carcinogens. Cytokines are small proteins. These proteins are released by some of the cells in the immune system, and are vital to signalling pathways in the body of mammals. STAT3 is very important in the activation of the expression of certain mediators in the liver. STAT3 binds at the phosphotyrosine receptor which in turn phosphorylates tyrosine 705 at the C-terminal domain of STAT3, activating STAT3. If a receptor is missing tyrosine-kinase activity it will find tyrosine-kinases that are associated to the receptor, including JAK and Src when it is time for ligand engagement. Thanks to this recruitment, STAT3 is phosphorylated through the tyrosine phosphorylation cascade. This means that STAT3 is now activated, and its compounds disconnect from the receptor site, and relocate to the nucleus. Once there, the compounds bind to DNA response elements, and take part in many processes against target genes, such as apoptosis and cell proliferation, regulating their transcription.