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Showing 111 - 120 of 48700 pathways
SMPDB ID Pathway Chemical Compounds Proteins


Pw000053 View Pathway

Vitamin B6 Metabolism

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.


Pw000015 View Pathway

Caffeine Metabolism

Caffeine is obtained from diet including coffee and other beverages and is absorbed in the stomach and small intestine. In the liver, the cytochrome P450 oxidase enzyme system and specifically CYP1A2 metabolizes caffeine into paraxanthine to increase lipolysis and increase free fatty acids and glycerol levels in the blood, theobromine to dilate blood vessels and increase urine volume and theophylline which relaxes bronchi smooth muscles. In the lysosome, these metabolites undergo further metabolism into methyluric acids before being excreted in the urine. There is genetic variability in the metabolism of caffeine due to the polymorphism of CYP1A2. This variability can affect the pharmacokinetic and pharmacodynamic properties of caffeine and may affect an individual's consumption.


Pw000142 View Pathway

Tyrosine Metabolism

The tyrosine metabolism pathway describes the many ways in which tyrosine is catabolized or transformed to generate a wide variety of biologically important molecules. In particular, tyrosine can be metabolized to produce hormones such as thyroxine and triiodothyronine or it can be metabolized to produce neurotransmitters such as L-DOPA, dopamine, adrenaline, or noradrenaline. Tyrosine can also serve as a precursor of the pigment melanin and for the formation of Coenzyme Q10. Additionally, tyrosine can be catabolized all the way down into fumarate and acetoacetate. This particular pathway for tyrosine degradation starts with an alpha-ketoglutarate-dependent transamination reaction of tyrosine, which is mediated through the enzyme known as tyrosine transaminase. This process generates p-hydroxyphenylpyruvate. This aromatic acid is then acted upon by p-hydroxylphenylpyruvate-dioxygenase which generates the compound known as homogentisic acid or homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a unique dioxygenase enzyme known as homogentisic acid 1,2-dioxygenase is required. Through this enzyme, maleylacetoacetate is created from the homogentisic acid precursor. The accumulation of excess homogentisic acid and its oxide (named alkapton) in the urine of afflicted individuals can lead to a condition known as alkaptonuria. This genetic condition, also known as an inborn error of metabolism or IEM, occurs if there are mutations in the homogentisic acid 1,2-dioxygenase gene. After the breakdown of homogentisate is achieved, maleylacetoacetate is then attacked by the enzyme known as maleylacetoacetate-cis-trans-isomerase, which generates fumarylacetate. This isomerase catalyzes the rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase uses glutathione as a coenzyme or cofactor. The resulting product, fumarylacetoacetate, is then split into acetoactate and fumarate via the enzyme known as fumarylacetoacetate-hydrolase through the addition of a water molecule. Through this set of reactions fumarate and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA, which in turn can be oxidized by the citric acid cycle (also known as the TCA cycle) or used for fatty acid synthesis. Other aspects of tyrosine metabolism include the generation of catecholamines. In this process, the enzyme known as tyrosine hydroxylase (or AAAH or TYH) catalyzes the conversion of tyrosine to L-DOPA. The L-DOPA can then be converted via the enzyme DOPA decarboxylase (DDC) to dopamine. Dopamine can then be converted to 3-methoxytyramine via the action of catechol-O-methyltransferase (COMT). Dopamine can also be converted to norepinephrine (noradrenaline) through the action of the enzyme known as dopamine beta hydroxylase (DBH). Norepinephrine can then be converted to epinephrine (adrenaline) through the action of phenyethanolamine N-methyltransferase (PNMT). Catecholamines such as L-DOPA, dopamine and methoxytyramine are produced mainly by the chromaffin cells of the adrenal medulla and by neuronal cells found in the brain. For example, dopamine, which acts as a neurotransmitter, is mostly produced in neuronal cell bodies in the ventral tegmental area and the substantia nigra while epinephrine is produced in neurons in the human brain that express PMNT. Catecholamines typically have a half-life of a few minutes in the blood. They are typically degraded via catechol-O-methyltransferases (COMT) or by deamination via monoamine oxidases (MAO). Another important aspect of tyrosine metabolism includes the production of melanin. Melanin is produced through a mechanism known as melanogenesis, a process that involves the oxidation of tyrosine followed by the polymerization of these oxidation by-products. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are three types of melanin: pheomelanin, eumelanin, and neuromelanin of which eumelanin is the most common. Melanogenesis, especially in the skin, is initiated through the exposure to UV light. Melanin is the primary pigment that determines skin color. Melanin is also found in hair and the pigmented tissue underlying the iris. The first step in the synthesis for both eumelanins and pheomelanins is the conversion of tyrosine to dopaquinone by the enzyme known as tyrosinase. The resulting dopaquinone can combine with cysteine to produce cysteinyldopa, which then polymerizes to form pheomelanin. Dopaquinone can also form lecuodopachrome, which then can be converted to dopachrome (a cyclization product) and this eventually becomes eumelanin. Tyrosine plays a critical role in the synthesis of thyroid hormones. Thyroid hormones are produced and released by the thyroid gland and include triiodothyronine (T3) and thyroxine (T4). These two hormones are responsible for regulating metabolism. Thyroxine was discovered and isolated by Edward Calvin Kendall in 1915. Thyroid hormones are produced by the follicular cells of the thyroid gland through the action of thyroperoxidase, which iodinates reactive tyrosine residues on thyroglobulin. Proteolysis of the thyroglobulin in cellular lysosomes releases the small molecule thyroid hormones. In mammals, tyrosine can be formed from dietary phenylalanine by the enzyme phenylalanine hydroxylase, found in large amounts in the liver. Phenylalanine is considered an essential amino acid, while tyrosine (which can be endogenously synthesized) is not. In plants and most microbes, tyrosine is produced via prephenate, an intermediate that is produced as part of the shikimate pathway.


Pw122285 View Pathway

Pancreas Function - Beta Cell

Beta cells are found in pancreatic islet cells and their main function is to release insulin. Insulin counteracts glucagon and functions to maintain glucose homeostasis when glucose levels are high. Insulin is contained in granules in the cell as a reserve ready to be released, which is dependent on extracellular glucose levels, and intracellular calcium levels and/or various proteins that activate the vesicle-associated membrane protein on the insulin granules' membranes. In the process of insulin secretion, glucose must first undergo glycolysis to increase ATP in the cell. The inside of the beta cell then becomes electrically positive due to the closure of potassium channels that were inhibited by ATP. From this closure, the potassium is no longer being shuttled out of the cell, thus depolarizing the cell due to the extra intracellular potassium. The resulting action potential from the increased membrane potential causes the voltage gate calcium channels to open, creating an influx of calcium into the cell. This triggers the vesicle-associated membrane protein on the outside of the insulin granule to tether, dock, and fuse with the beta cell membrane. Insulin is then exocytosed from the cell. However, the vesicle-associated membrane protein can be activated by other means in addition to calcium. Acetylcholine can bind to muscarinic acetylcholine receptors on the cell membrane and trigger a G protein cascade. This eventually leads to the activation of inositol trisphosphate to cause calcium release from the rough endoplasmic reticulum so that it can activate the calcium/calmodulin-dependent protein kinase to trigger the vesicle-associated membrane protein. The G protein cascade can also lead to the activation of diacylglycerol and subsequently protein kinase C to lead to the same outcome. Glucagon-like peptide can also trigger a similar G protein cascade when it binds to glucagon-like peptide receptors on the cell membrane of the beta cell. This process involves cAMP and a few other proteins in order to lead to the same eventual outcome of triggering the vesicle-associated membrane protein and the exocytosis of insulin from the beta cell.


Pw000159 View Pathway

Galactose Metabolism

This pathway depicts the conversion of galactose into glucose, lactose, and other sugar intermediates that may be used for a range of metabolic process. Dietary sources of galactose are numerous, but some of the primary sources in the human diet can be found in milk and milk derivative products. This is because during digestion milk sugars and lactose are hydrolyzed into their molecular constituents (e.g. base monosaccharides). In milk, such monosaccharides include glucose and galactose. The metabolism of the sugar Galactose is occurs almost entirely in the liver, and its metabolism is the consequence of three steps or reactions. First, the phosphorylation of galactose is induced by a special enzyme with the predictable name, galactokinase, and produces galactose 1-phosphate. Second, this biproduct and a second molecule, UDP-glucose, undergo a reaction which leads to the formation of UDP-galactose and glucose 1-phosphate. Thus, this reaction produces 1 molecule of glucose 1-phosphate per molecule of galactose. This is mediated by the enzyme galactose-1-phosphate uridylyltransferase (GALT). The resulting UDP-galactose undergoes epimerization to form UDP-glucose via the enzyme UDP-galactose-4 epimerase (GALE). The UDP-glucose can be used in glucuronidation reactions and other pentose interconversions. In a reaction shared with other pathways, glucose 1-phosphate can be converted into glucose 6-phosphate. There are other pathways associated with galactose metabolism. For instance, galactose can be converted into UDP-glucose by the sequential activities of GALK, UDP-glucose pyrophosphorylase 2 (UGP2), and GALE. Galactose can also be reduced to galactitol by NADPH-dependent aldose reductase. Also shown in this pathway is the conversion of glucose to galactose vis a vis a different process to the ones described earlier. This pathway, called hexoneogenesis, allows mammary glands to produce galactose. It should be noted however, that despite the existence of this pathway of galactose production, the vast majority of galactose in breast milk is actually the result of direct uptake up from the blood, whereas only a small fraction, ~35%, is the result of this de novo process hexoneogenesis. Also depicted in this pathway are the conversions of other dietary di and tri-saccharides (raffinose, manninotriose, melibiose, stachyose) into galactose, glucose and fructose as well as and dietary sugar alcohols (melibitol, galactinol, galactosylglycerol) into sorbitol, myo-inositol, and glycerol.


Pw000046 View Pathway

Glucose-Alanine Cycle

The glucose-alanine cycle—also referred to in the literature as the Cahill cycle or the alanine cycle—involves muscle protein being degraded to provide more glucose to generate additional ATP for muscle contraction. It allows pyruvate and glutamate to be transported out of muscle tissue to the liver where gluconeogenesis takes place to supply the muscle tissue with more glucose as mentioned previously. To initiate the cycle, muscle and tissues that catabolize amino acids for fuel generate amino groups—most commonly in the form of glutamate—through the process of transamination. These amino groups are transferred via alanine aminotransferase to pyruvate (a product of glycolysis) to form alanine and alpha-ketoglutarate. Alanine subsequently moves through the circulatory system to the liver where the reaction previously catalyzed by alanine aminotransferase is reversed to produce pyruvate. This pyruvate is converted into glucose through the process of gluconeogenesis which subsequently is transported back to the muscle tissue. Meanwhile, glutamate dehydrogenase in the mitochondria catabolizes glutamate into ammonium. Ammonium moves on to form urea in the urea cycle.


Pw000041 View Pathway

Phytanic Acid Peroxisomal Oxidation

Phytanic acid, a branched chain fatty acid, is an important component of fatty acid intake, occuring in meat, fish and dairy products. Due to its methylation, it cannot be a substrate for acyl-CoA dehydrogenase and cannot enter the mitochondrial beta oxidation pathway. Phytanic acid is instead activated to its CoA ester form by a CoA synthetase to phytanoyl-CoA, where it can begin the first cycle of alpha oxidation. Phytanoyl-CoA is a substrate for a specific alpha-hydroxylase (Phytanoyl-CoA hydroxylase), which adds a hydroxyl group to the α-carbon of phytanic acid, creating the 19-carbon homologue, pristanic acid. Pristanic acid then undergoes further metabolism through beta oxidation.


Pw000692 View Pathway

Methylhistidine Metabolism

Methylhistidine is a modified amino acid that is produced in myocytes during the methylation of actin and myosin. It is also formed from the methylation of L-histidine, which takes the methyl group from S-adenosylmethionine and forms S-adenosylhomocysteine as a byproduct. After its formation in the myocytes, methylhistidine enters the blood stream and travels to the kidneys, where it is excreted in the urine. Methylhistidine is present in the blood and urine in higher concentrations after skeletal muscle protein breakdown, which can occur due to disease or injury. Because of this, it can be used to judge how much muscle breakdown is occurring. Methylhistidine levels are also affected by diet, and may differ between vegetarian diets and those containing meats.


Pw000161 View Pathway

Beta Oxidation of Very Long Chain Fatty Acids

The degradation of fatty acids occurs is many ways, but for the most part in most species it occurs mainly through the beta-oxidation cycle. Take mammals for example, in this subset of species we find that beta-oxidation takes place not only in mitochondria, but in peroxisomes as well. In contrast, it tends to be the case that in plants and fungi beta-oxidation is only seen in peroxisomes. The reason the beta-oxidation cycle is found to occur in both mitochondria and peroxisomes in mammals is thought to be that extremely long chain fatty acids will in fact undergo oxidation in both locations, an initial or first oxidation in peroxisomes and second oxidation in the mitochondria. There is however a difference between the oxidation cycle which occurs in both these organelles. Namely, that the oxidation undergone in peroxisomes does not have any coupling to ATP synthesis, unlike the corresponding oxidation which occurs in the mitochondria. We find rather that electrons are passed to molecules of oxygen, which produces hydrogen peroxide. Moreover, there is an enzyme which is found only peroxisomes which ties into this process. It can turn hydrogen peroxide back into water and oxygen and is catalase. To expound further the differences between the oxidation cycle found in the peroxisomes and the mitchondria consider the following three key differences. One, in the peroxisome the beta-oxidation cycle takes as a necessary input a special enzyme called, peroxisomal carnitine acyltransferase, which is needed to move an activated acyl group from outside the peroxisome to inside it. In mitochondrial oxidation similar but different enzymes are used called carnitine acyltransferase I and II. Difference number two is that oxidation in the peroxisome commences with catalysis induced by an enzyme called acyl CoA oxidase. Also, it should be noted that another enzyme called beta-ketothiolase which aids in peroxisomal beta-oxidation has a substrate specificity which differs from that of the mitochondrial beta-ketothiolase. Turning now to how the oxidation cycle function in mitochondria, note that the mitochondrial beta-oxidation pathway is composed of four repeating reactions that take place with each fatty acid molecule. The oxidation of fatty acid chains is a process of progress through repetition. With each turn of the cycle two carbons are removed from the fatty acid chain and the energy of the chemical bonds once housed by the molecule is captured by the reduced energy carriers NADH and FADH2. Acetyl-CoA is created in this 4 step reaction beta-oxidation process and is sent to the TCA cycle. Once inside the TCA cycle, the process of oxidation continues until even the acetyl-CoA is oxidized to CO2. More NADH and FADH2 result.


Pw016768 View Pathway

De Novo Triacylglycerol Biosynthesis

A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. De novo biosynthesis of triglycerides is also known as the phosphatidic acid pathway, and it is mainly associated with the liver and adipose tissue. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). The next three steps are localized to the endoplasmic reticulum membrane. The enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. Next, magnesium-dependent phosphatidate phosphatase catalyzes the conversion of phosphatidic acid into diacylglycerol. Last, the enzyme diacylglycerol O-acyltransferase synthesizes triacylglycerol from diacylglycerol and a fatty acyl-CoA.
Showing 111 - 120 of 48700 pathways