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Pathways

Showing 1 - 10 of 61345 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP63697

Pw064679 View Pathway
metabolic

Phosphatidylethanolamine Biosynthesis

Mus musculus
Phosphatidylethanolamines (PE) are a class of phospholipids that incorporate a phosphoric acid headgroup into a diacylglycerol backbone. They are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In Homo sapiens, there exist two phosphatidylethanolamine biosynthesis pathways. In the visualization, all enzymes that are dark green in colour are membrane-localized. The first pathway synthesizes phosphatidylethanolamine from ethanolamine via the Kennedy pathway. First, the cytosol-localized enzyme choline/ethanolamine kinase catalyzes the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Phosphatidylethanolamine is also synthesized from phosphatidylserine at the mitochondrial inner membrane by phosphatidylserine decarboxylase. Phosphatidylserine, itself, is synthesized using a base-exchange reaction with phosphatidylcholine. This reaction is catalyzed by phosphatidylserine synthase which is located in the endoplasmic reticulum membrane.

SMP63696

Pw064678 View Pathway
metabolic

Estrone Metabolism

Mus musculus
Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue. Estrone metabolism primarily occurs in the endoplasmic reticulum (membrane-associated enzymes are coloured dark green in the image). Estrone is conjugated into estrogen conjugates such as estrone sulfate and estrone glucuronide by sulfotransferases and glucuronidases, and can also be hydroxylated by cytochrome P450 enzymes into catechol estrogens such as 2-hydroxyestrone (Wikipedia). The enzyme catechol O-methyltransferase catalyzes the conversion of 2-hydroxyestrone into 2-methoxyestrone which is used to synthesize 2-methoxyestrone 3-glucuronide via the membrane-associated massive multimer UDP-glucuronosyltransferase 1-1. Estrone can also be reversibly converted into estradiol by estradiol 17-beta-dehydrogenase 1. This same enzyme can reversibly convert 16a-hydroxyestrone (synthesized from estrone via cytochrome P450 3A5) into estriol. Estriol is alternatively synthesized from estradiol via cytochrome P450 3A5.

SMP63694

Pw064676 View Pathway
metabolic

De Novo Triacylglycerol Biosynthesis

Mus musculus
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other animals, as well as vegetable fat. They are also present in the blood to enable the bidirectional transference of adipose fat and blood glucose from the liver, and are a major component of human skin oils. (Wikipedia) 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.

SMP63693

Pw064675 View Pathway
metabolic

Tryptophan Metabolism

Mus musculus
Tryptophan is an essential amino acid. This means that it cannot be synthesized by the organism and therefore must be part of its diet. Amino acids, including tryptophan, act as building blocks in protein biosynthesis through the action of tryptophanyl tRNA synthetase. In addition, tryptophan functions as a biochemical precursor for serotonin (a neurotransmitter), which is synthesized via tryptophan hydroxylase. Serotonin, in turn, can be converted to melatonin (a neurohormone), via N-acetyltransferase and 5-hydroxyindole-O-methyltransferase activities. Niacin via synthesized from tryptophan via kynurenine and quinolinic acids as key biosynthetic intermediates. Kynurenine is the first key branch point intermediate in tryptophan’s catabolic pathway leading to 3 fates: First, kynurenine can undergo deamination in a standard transamination reaction yielding kynurenic acid. Secondly, kynurenine can undergo a series of catabolic reactions producing 3-hydroxyanthranilate plus alanine. In this reaction, kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine—oxoglutarate transaminase (also known as Kynurenine amino-transferase and glutamine transaminase K, GTK) catabolizes its conversion into kynurenic acid and kynurenine 3-hydroxylase - to 3-hydroxykynurenine. The oxidation of 3-hydroxyanthranilate converts it into 2-amino-3-carboxymuconic 6-semialdehyde, which has two fates, it can either degrade to acetoacetate or it can cyclize to quinolate. Most of the body’s 3-hydroxyanthranilate leads to acetoacetate which is why tryptophan is also a ketogenic amino acid. An important side reaction in liver involves a non-enzymatic cyclization to quinolate then via a transamination and several rearrangements yields limited amounts of nicotinic acid, which leads to production of a small amount of NAD+ and NADP+.

SMP63692

Pw064674 View Pathway
metabolic

Phosphatidylcholine Biosynthesis

Mus musculus
Phosphatidylcholines (PC) are a class of phospholipids that incorporate a phosphocholine headgroup into a diacylglycerol backbone. They are the most abundant phospholipid in eukaryotic cell membranes and has both structural and signalling roles. In eukaryotes, there exist two phosphatidylcholine biosynthesis pathways: the Kennedy pathway and the methylation pathway. The Kennedy pathway begins with the direct phosphorylation of free choline into phosphocholine followed by conversion into CDP-choline and subsequently phosphatidylcholine. It is the major synthesis route in animals. The methylation pathway involves the 3 successive methylations of phosphatidylethanolamine to form phosphatidylcholine. The first reaction of the Kennedy pathway involves the cytosol-localized enzyme choline/ethanolamine kinase catalyzing the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. A parallel Kennedy pathway forms phosphatidylethanolamine from ethanolamine - the only difference being a different enzyme, ethanolamine-phosphate cytidylyltransferase, catalyzing the second step. Phosphatidylethanolamine is also synthesized from phosphatidylserine in the mitochondrial membrane by phosphatidylserine decarboxylase. Phosphatidylethanolamine funnels into the methylation pathway in which phosphatidylethanolamine N-methyltransferase (PEMT) then catalyzes three sequential N-methylation steps to convert phosphatidylethanolamine to phosphatidylcholine. PEMT uses S-adenosyl-L-methionine as a methyl donor.

SMP63691

Pw064673 View Pathway
metabolic

Cardiolipin Biosynthesis

Mus musculus
Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism. (Wikipedia) Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. 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). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

SMP63690

Pw064672 View Pathway
metabolic

Sulfate/Sulfite Metabolism

Mus musculus
This pathway illustrates the conversion of sulfite to sulfate (via sulfate oxidase) and subsequent generation of adenylylsulfate (APS) via 3'-phosphoadenosine 5'-phosphosulfate synthase 2. APS is converted to phosphoadenylyl-sulfate (PAPS) via adenylylsulfate kinase. APS can also be regenerated from PAPS by 3'(2'), 5'-bisphosphate nucleotidase 1. PAPS is eventually converted to adenosine bisophosphate (PAP) through the action of several different enzymes including aryl sulfotransferase, chondroitin 4-sulfotransferase 13 and estrone sulfotransferase. Sulfites are defined as compounds that contain the sulfite ion SO2−. The sulfite ion is the conjugate base of sulfurous acid. Sulfites occur naturally in all wines. Sulfites are commonly introduced to arrest fermentation at a desired time, and may also be added to wine as preservatives to prevent spoilage and oxidation at several stages of winemaking. Sulfites are also used as preservatives in dried fruits, and dried potato products.

SMP63689

Pw064671 View Pathway
metabolic

Valine, Leucine and Isoleucine Degradation

Mus musculus
Valine, Isoleuciine and Leucine are essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids must be obtained from the diet. The catabolism of all three amino acids starts in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with α-ketoglutarate as the amine acceptor. As a result, three different α-keto acids are produced and are oxidized using a common branched-chain α-keto acid dehydrogenase (BCKD), yielding the three different CoA derivatives. Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine. These acyl-CoA’s undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge. Leucine is ultimately converted to acetyl-CoA and acetoacetate; isoleucine to acetyl-CoA and succinyl-CoA; and valine to propionyl-CoA (and subsequently succinyl-CoA). Under fasting conditions, substantial amounts of all three amino acids are generated by protein breakdown. In muscle, the final products of leucine, isoleucine, and valine catabolism can be fully oxidized via the citric acid cycle; in liver they can be directed toward the synthesis of ketone bodies (acetoacetate and acetyl-CoA) and glucose (succinyl-CoA). Because isoleucine catabolism terminates with production of acetylCoA and propionylCoA it is both glucogenic and ketogenic. Because leucine gives rise to acetylCoA and acetoacetylCoA, it is classified as strictly ketogenic.

SMP63688

Pw064670 View Pathway
metabolic

Androstenedione Metabolism

Mus musculus
Androstenedione is an endogenous weak androgen steroid hormone that is a precursor of testosterone and other androgens, as well as of estrogens like estrone (Wikipedia). Its metabolism occurs primarily in the endoplasmic reticulum (membrane-associated enzymes are coloured dark green in the image). Conversion of androstenedione to testosterone requires the enzyme testosterone 17-beta-dehydrogenase 3. Conversion of androstenedione to estrone involves three successive reactions catalyzed by the enzyme aromatase (cytochrome P450 19A1). Androstenedione can also be converted into etiocholanolone glucuronide, androsterone glucuronide, and adrenosterone. The three-reaction subpathway to synthesize etiocholanolone glucuronide begins with the enzyme 3-oxo-5-beta-steroid 4-dehydrogenase catalyzing the conversion of androstenedione to etiocholanedione. This is followed by the conversion of etiocholanedione to etiocholanolone which is catalyzed by aldo-keto reductase family 1 member C4. Lastly, the large membrane-associated multimer UDP-glucuronosyltransferase 1-1 catalyzes the conversion of etiocholanolone to etiocholanolone glucuronide. The three-reaction subpathway to synthesize androsterone glucuronide begins with the conversion of androstenedione to androstanedione via 3-oxo-5-alpha-steroid 4-dehydrogenase 1. Anstrostanedione is then converted into androsterone via aldo-keto reductase family 1 member C4. The last reaction to form androsterone glucuronide is catalyzed by the large multimer UDP-glucuronosyltransferase 1-1. The two-reaction subpathway to synthesize adrenosterone begins in the mitochondrial inner membrane where androstenedione is first converted into 11beta-hydroxyandrost-4-ene-3,17-dione by the enzyme cytochrome P450 11B1. Following transport to the endoplasmic reticulum, 11beta-hydroxyandrost-4-ene-3,17-dione is converted into adrenosterone via corticosteroid 11-beta-dehydrogenase isozyme 1.

SMP63686

Pw064668 View Pathway
metabolic

Urea Cycle

Mus musculus
About 80% of the body’s excreted nitrogen is in the form of urea which is also largely made in the liver, in a series of reactions that are distributed between the mitochondrial matrix and the cytosol. The series of reactions that form urea is known as the Urea Cycle (Ornithine Cylce) or the Krebs-Henseleit Cycle. The essential features of the urea cycle reactions and their metabolic regulation are as follows: Arginine from the diet or from protein breakdown is cleaved by the cytosolic enzyme arginase, generating urea and ornithine. In subsequent reactions of the urea cycle a new urea residue is built on the ornithine, regenerating arginine and perpetuating the cycle. Ornithine arising in the cytosol is transported to the mitochondrial matrix, where ornithine transcabamoylase catalyzes the condensation of ornithine with carbamoyl phosphate, producing citrulline. The energy for the reaction is provided by the high-energy anhydride of carbamoyl phosphate. The product, citrulline, is then transported to the cytosol, where the remaining reactions of the cycle take place. The synthesis of citrulline requires a prior activation of carbon and nitrogen as carbamoyl phosphate (CP). The activation step requires 2 equivalents of ATP and the mitochondrial matrix enzyme carbamoyl phosphate synthetase-I (CPS-I). In a 2-step reaction, catalyzed by cytosolic argininosuccinate synthetase, citrulline and aspartate are condensed to form argininosuccinate. The reaction involves the addition of AMP (from ATP) to the amido carbonyl of citrulline, forming an activated intermediate on the enzyme surface (AMP-citrulline), and the subsequent addition of aspartate to form argininosuccinate. Arginine and fumarate are produced from argininosuccinate by the cytosolic enzyme argininosuccinate lyase. In the final step of the cycle arginase cleaves urea from aspartate, regenerating cytosolic ornithine, which can be transported to the mitochondrial matrix for another round of urea synthesis. The fumarate, generated via the action of arginiosuccinate lyase, is reconverted to aspartate for use in the argininosuccinate synthetase reaction.
Showing 1 - 10 of 61345 pathways