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Showing 1 - 10 of 49827 pathways
SMPDB ID Pathway Chemical Compounds Proteins


Pw000185 View Pathway

Citrullinemia Type I

Citrullinemia Type 1, also called argininosuccinate synthetase deficiency, argininosuccinic acid synthetase deficiency or ASS deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a deficiency of argininosuccinate synthetase. Argininosuccinate synthetase is an important enzyme in the process of removing nitrogen from the body. This disorder is characterized by a large accumulation of ammonia in the blood as well as other bodily fluids . Symptoms of the disorder include vomiting, lethargy and intracranial pressure. Treatment with protein restriction and intravenous administration of arginine can help manage symptoms, and diet management throughout the patient’s life can also show improvement. It is estimated that citrullinemia type 1 affects 1 in 57,000 individuals.


Pw000191 View Pathway

Carbamoyl Phosphate Synthetase Deficiency

CCarbamoyl Phosphate Synthetase Deficiency, also called hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a defective CPS1 gene. The CPS1 gene codes for the protein carbamoyl phosphate synthetase I, which plays a role in the urea cycle. This disorder is characterized by a large accumulation of ammonia in the blood. Symptoms of the disorder include unusual movements, seizures, unusual sleeping or coma. Treatment with citrulline or arginine, which maintains a regular rate of protein creation. It is estimated that carbamoyl phosphate synthetase deficiency affects 1 in 800,000 individuals in Japan.


Pw000184 View Pathway

Argininosuccinic Aciduria

Argininosuccinic Aciduria, (Argininosuccinase Deficiency, Argininosuccinate Lyase Deficiency, ASL Deficiency) is an autosomal recessive disorder caused by a mutation in the ASL gene which codes for argininosuccinate lyase. It results in accumulation of citrulline, arginosuccinic acid, L-arginine, and L-glutamic acid in plasma as well as ammonia in blood. Infants are lethargic and unwilling to eat. They may develop seizures, coma, and failure to thrive as toxic ammonia accumulates.


Pw000157 View Pathway

Glycine and Serine Metabolism

This pathway describes the synthesis and breakdown of several small amino acids, including glycine, serine, and cysteine. All of these compounds share common intermediates and almost all can be biosynthesized from one another. Serine and glycine are not essential amino acids and can be synthesized from several routes. On the other hand, cysteine is a conditionally essential amino acid, meaning that it can be endogenously synthesized but insufficient quantities may be produced due to certain diseases or conditions. Serine is central to the synthesis and breakdown of the other two amino acids. Serine can be synthesized via glycerate, which can be converted into glycerate 3-phosphate (via glycerate kinase), which in turn is converted into phosphohydroxypyruvate by phosphoglycerate dehydrogenase and then phosphoserine (via phosphoserine transaminase) and finally to serine (via phosphoserine phosphatase). The serine synthesized via this route can be used to create cysteine and glycine through the homocysteine cycle. In the homocysteine cycle, cystathionine beta-synthase catalyzes the condensation of homocysteine and serine to give cystathionine. Cystathionine beta-lyase then converts this double amino acid to cysteine, ammonia, and alpha-ketoglutarate. Glycine is biosynthesized in the body from the amino acid serine. In most organisms, the enzyme serine hydroxymethyltransferase (SHMT) catalyzes this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. Glycine can be degraded via three pathways. The predominant pathway in animals involves the glycine cleavage system, also known as the glycine decarboxylase complex or GDC. This system is usually triggered in response to high concentrations of glycine. The system is sometimes referred to as glycine synthase when it runs in the reverse direction to produce glycine. The glycine cleavage system consists of four weakly interacting proteins: T, P, L and H-proteins. The glycine cleavage system leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step in this degradation pathway is the reverse of glycine biosynthesis from serine with serine hydroxymethyltransferase (SHMT). The serine generated via glycine is then converted into pyruvate by the enzyme known as serine dehydratase. In the third route to glycine degradation, glycine is converted into glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase into oxalate in an NAD+-dependent reaction.


Pw000140 View Pathway

Pterine Biosynthesis

Folates are very important cofactors that provide support for many biosynthetic reactions. The reactions depicted in this pathway include reactions that are paired with transports, within the cell, travelling intracellularly, which allows folate to be absorbed by cells, as well as the synthesis of pterines, which are used in folate synthesis. Two branches are depicted: Pterin synthesis and Folate biosynthesis. In pterin synthesis, GTP is the precursor for pterin biosynthesis. In the first reaction, GTP cyclohydrolase acts to create formamidopyrimidine nucleoside triphosphate from guanosine triphosphate, which is provided from the purine metabolism pathway. Formamidopyrimidine nucleoside triphosphate then uses GTP cyclohydrolase again to create 2,5-diaminopyrimidine nucleoside triphosphate. GTP cyclohydrolase then works with 2,5-diaminopyrimidine nucleoside triphosphate to produce 2,3-diamino-6-(5’-triphosphoryl-3’,4’-trihydroxy-2’-oxopentyl)-amino-4-oxopyrimidine, which is then converted by GTP cyclohydrolase to dihydroneopterin triphosphate. Dihydroneopterin is then transported to the mitochondria and subsequently catalyzed into dyspropterin, which then exits the mitochondria to continue pterin biosynthesis. Once having been transported from the mitochondria, dyspropterin uses sepiapterin reductase, aldose reductase and carbonyl reductase [NADPH] 1 to create 6-lactoyltetrahydropterin. This compound then undergoes 2 reactions, the first being sepiapterin reductase converting 6-lactoyltetrahydropterin into tetrahydrobiopterin, the second being 6-lactoyltetrahydropterin being converted to sepiapterin. Both branches of pterin reactions then respectively end in the creation of neopterin and dihydrobiopterin.


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.


Pw000011 View Pathway

beta-Alanine Metabolism

Beta-alanine, 3-aminopropanoic acid, is a non-essential amino acid. Beta-Alanine is formed by the proteolytic degradation of beta-alanine containing dipeptides: carnosine, anserine, balenine, and pantothenic acid (vitamin B5). These dipeptides are consumed from protein-rich foods such as chicken, beef, pork, and fish. Beta-Alanine can also be formed in the liver from the breakdown of pyrimidine nucleotides into uracil and dihydrouracil and then metabolized into beta-alanine and beta-aminoisobutyrate. Beta-Alanine can also be formed via the action of aldehyde dehydrogenase on beta-aminoproionaldehyde which is generated from various aliphatic polyamines. Under normal conditions, beta-alanine is metabolized to aspartic acid through the action of glutamate decarboxylase. It addition, it can be converted to malonate semialdehyde and thereby participate in propanoate metabolism. Beta-Alanine is not a proteogenic amino acid. This amino acid is a common athletic supplementation due to its belief to improve performance by increased muscle carnosine levels.


Pw000042 View Pathway

Phenylalanine and Tyrosine Metabolism

In man, phenylalanine is an essential amino acid which must be supplied in the dietary proteins. Once in the body, phenylalanine may follow any of three paths. It may be (1) incorporated into cellular proteins, (2) converted to phenylpyruvic acid, or (3) converted to tyrosine. Tyrosine is found in many high protein food products such as soy products, chicken, turkey, fish, peanuts, almonds, avocados, bananas, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds, and sesame seeds. Tyrosine can be converted into L-DOPA, which is further converted into dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Depicted in this pathway is the conversion of phenylalanine to phenylpyruvate (via amino acid oxidase or tyrosine amino transferase acting on phenylalanine), the incorporation of phenylalanine and/or tyrosine into polypeptides (via tyrosyl tRNA synthetase and phenylalyl tRNA synthetase) and the conversion of phenylalanine to tyrosine via phenylalanine hydroxylase. This reaction functions both as the first step in tyrosine/phenylalanine catabolism by which the body disposes of excess phenylalanine, and as a source of the amino acid tyrosine. The decomposition of L-tyrosine begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The next oxidation step catalyzed by p-hydroxylphenylpyruvate-dioxygenase creates homogentisate. In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase, is required to create maleylacetoacetate. Fumarylacetate is created by the action maleylacetoacetate-cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally split via fumarylacetoacetate-hydrolase into fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate).


Pw000009 View Pathway

Ammonia Recycling

Ammonia can be rerouted from the urine and recycled into the body for use in nitrogen metabolism. Glutamate and glutamine play an important role in this process. There are many other processes that act to recycle ammonia. asparaginase recycles ammonia from asparagine. Glycine cleavage system generates ammonia from glycine. Histidine ammonia lyase forms ammonia from histidine. Serine dehydratase also produces ammonia by cleaving serine.


Pw000031 View Pathway

Nucleotide Sugars Metabolism

Nucleotide sugars are defined as any nucleotide in which the distal phosphoric residue of a nucleoside 5'-diphosphate is in glycosidic linkage with a monosaccharide or monosaccharide derivative. There are nine sugar nucleotides and they can be classified depending on the type of the nucleoside forming them: UDP-Glc, UDP-Gal, UDP-GlcNAc, UDP-GlcUA, UDP- Xyl, GDP-Man, GDP-Fuc and CMP-NeuNAc. Turning back now to the pathway in question, namely the nucleotide sugar metabolism pathway, it should be noted that the nucleotide sugars play an important role. Indeed, they are donors of certain important residues of sugar which are vital to glycosylation and by extension tot the production of polysaccharides. This process produces the substrates for glycosyltransferases. These sugars have several additional roles. For example, nucleotide sugars serve a vital purpose as the intermediates in interconversions of nucleotide sugars that result in the creation and activation of certain sugars necessary in the glycosylation reaction in certain organisms. Moreover, the process of glycosylation is attributed mostly (though not entirely) to the endoplasmic reticulum/golgi apparatus. Logically then, due to the important role of nucleotide sugars in glycosylation, a plethora of transporters exist which displace the sugars from their point of production, the cytoplasm, to where they are needed. In the case, the endoplasmic reticulum and golgi apparatus.
Showing 1 - 10 of 49827 pathways