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Showing 21 - 30 of 49833 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000007

Pw000011 View Pathway
Metabolic

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.

SMP0000070

Pw000035 View Pathway
Metabolic

Riboflavin Metabolism

Riboflavin (vitamin B2) is an important part of the enzyme cofactors FAD (flavin-adenine dinucleotide) and FMN (flavin mononucleotide). The name "riboflavin" actually comes from "ribose" and "flavin". Like the other B vitamins, riboflavin is needed for the breaking down and processing of ketone bodies, lipids, carbohydrates, and proteins. Riboflavin is found in many different foods, such as meats and vegetables.As the digestion process occurs, many different flavoproteins that come from food are broken down and riboflavin is reabsorbed. The reverse reaction is mediated by acid phosphatase 6. FMN can be turned into to FAD via FAD synthetase, while the reverse reaction is mediated by nucleotide pyrophosphatase. FAD and FMN are essential hydrogen carriers and are involved in over 100 redox reactions that take part in energy metabolism.

SMP0000008

Pw000042 View Pathway
Metabolic

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).

SMP0090879

Pw091899 View Pathway
Physiological

Hop Pathway in Cardiac Development

The transcription of DNA is aided in large part by something called "homeodomain transcription factors". They are a diverse group of DNA binding factors. In fact, genes which are created with the aid of homeodomain factors tend to conglomerate and are responsible for anterior-posterior patterning. There is much to be said as well regarding the development and growth of cardiac myocytes and homedomain transcription factors. Indeed, at the early stages of the cell differentiation of cardiac myoctes a delicate balance of joint expression of several factors is needed for correct development (namely: serum response factor (SRF), and GATA4) and a homeodomain factor known as Nkx2-5! The joint expression of the aforementioned factors is the critical in the development of myocytes as well as gene expression in the cardiac region. To underline the importance of the homeodomain transcription factors, note that an error in the Nkx2-5 gene has severe consequences, which include, though are not necessarily limited to, embryonic lethality, as well as severe problems in general heart development. To put all this in context of the pathway in question, Hop actually stands for (Homeodomain Only Protein). The Hop gene plays an important role in the cardiac development we have been describing, as it too encodes a homedomain factor which plays an important role at the onset stages of cardiac development. The Hop gene is downstream of the Mkx2-5 factor we discussed earlier, and similar to it, improper activation of Hop can lead to severe cardiac development issues. In mice for example, not have the Hop gene results in alterations to the cell cycle. In particular, cardiac cells are unable to exit the cycle at the correct stage and continue grow after normal developmental stage has finished. There exists an interesting symbiosis between Hop and SRF. First, Hop regulates gene expression by either binding to SRF or by preventing SRF binding to DNA. This occurs because Hop does not have anything to bind to DNA with, and as such must have different methods to regulate gene expression. Second, when Hop blocks normal SRF binding, the results is that the activation of genes in the heart is affected and normal development does not occur. In a nutshell, what can be said about this tango action of SRF and Hop is this: during the first stages of development, what is observed is that the Hop interaction is one which results in a cessation of the differentiation processes which are induced by SRF. In the later stages, it appears that Hop reduces cell proliferation which is normally caused by SRF.

SMP0000057

Pw000005 View Pathway
Metabolic

Citric Acid Cycle

The citric acid cycle, which is also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, is a connected series of enzyme-catalyzed chemical reactions of central importance to all aerobic organisms (i.e. organisms that use oxygen for cellular respiration). The citric acid cycle is named after citrate or citric acid, a tricarboxylic acid that is both consumed and regenerated through this pathway. The citric acid cycle was discovered in 1937 by Hans Adolf Krebs while he worked at the University of Sheffield in England (PMID: 16746382). Krebs received the Nobel Prize for his discovery in 1953. Krebs’ extensive work on this pathway is also why the citric acid or TCA cycle is often referred to as the Krebs cycle. Metabolically, the citric acid cycle allows the release of energy (ultimately in the form of ATP) from carbohydrates, fats, and proteins through the oxidation of acetyl-CoA. The citric acid cycle also produces CO2, the precursors for several amino acids (aspartate, asparagine, glutamine, proline) and NADH – all of which are used in other important metabolic pathways, such as amino acid synthesis and oxidative phosphorylation (OxPhos). The net yield of one “turn” of the TCA cycle in terms of energy-containing compounds is one GTP, one FADH2, and three NADH molecules. The NADH molecules are used in oxidative phosphorylation to generate ATP. In eukaryotes, the citric acid cycle occurs in the mitochondrial matrix. In prokaryotes, the citric acid cycle occurs in the cytoplasm. In eukaryotes, the citric acid or TCA cycle has a total of 10 steps that are mediated by 8 different enzymes. Key to the whole cycle is the availability of acetyl-CoA. One of the primary sources of acetyl-CoA is from the breakdown of glucose (and other sugars) by glycolysis. This process generates pyruvate. Pyruvate is decarboxylated by pyruvate dehydrogenase to generate acetyl-CoA. The citric acid cycle begins with acetyl-CoA transferring its two-carbon acetyl group to the four-carbon acceptor compound (oxaloacetate) to form a six-carbon compound (citrate) through the enzyme citrate synthase. The resulting citrate is then converted to cis-aconitate and then isocitrate via the enzyme aconitase. The resulting isocitrate then combines with NAD+ to form oxalosuccinate and NADH, which is then converted into alpha-ketoglutarate (and CO2) through the action of the enzyme known as isocitrate dehydrogenase. The resulting alpha-ketoglutarate combines with NAD+ and CoA-SH to produce succinyl-CoA, NADH, and CO2. This step is mediated by the enzyme alpha-ketoglutarate dehydrogenase. The resulting succinyl-CoA combines with GDP and organic phosphate to produce succinate, CoA-SH, and GTP. This phosphorylation reaction is performed by succinyl-CoA synthase. The resulting succinate then combines with ubiquinone to produce two compounds, fumarate and ubiquinol through the action of the enzyme succinate dehydrogenase. The resulting fumarate is then hydrated by the enzyme known as fumarase to produce malate. The resulting malate is oxidized via NAD+ to produce oxaloacetate and NADH. This oxidation reaction is performed by malate dehydrogenase. The resulting oxaloacetate can then combine with acetyl-CoA and the TCA reaction cycle begins again. Overall, in the citric acid cycle, the starting six-carbon citrate molecule loses two carboxyl groups as CO2, leading to the production of a four-carbon oxaloacetate. The two-carbon acetyl-CoA that is the “fuel” for the TCA cycle can be generated by several metabolic pathways including glucose metabolism, fatty acid oxidation, and the metabolism of amino acids. The overall reaction for the citric acid cycle is as follows: acetyl-CoA + 3 NAD+ + FAD + GDP + P + 2H2O = CoA-SH + 3NADH + FADH2 + 3H+ + GTP + 2CO2. Many molecules in the citric acid cycle serve as key precursors for other molecules needed by cells. The citrate generated via the citric acid cycle can serve as an intermediate for fatty acid synthesis; alpha-ketoglutarate can serve as a precursor for glutamate, proline, and arginine; oxaloacetate can serve as a precursor for aspartate and asparagine; succinyl-CoA can serve as a precursor for porphyrins; and acetyl-CoA can serve as a precursor fatty acids, cholesterol, vitamin D, and various steroid hormones. There are several variations to the citric acid cycle that are known. Interestingly, most of the variation lies with the step involving succinyl-CoA production or conversion. Humans and other animals have two different types of succinyl-CoA synthetases. One produces GTP from GDP, while the other produces ATP from ADP (PMID: 9765291). On the other hand, plants have a succinyl-CoA synthetase that produces ATP (ADP-forming succinyl-CoA synthetase) (Jones RC, Buchanan BB, Gruissem W. (2000). Biochemistry & molecular biology of plants (1st ed.). Rockville, Md: American Society of Plant Physiologists. ISBN 0-943088-39-9.). In certain acetate-producing bacteria, such as Acetobacter aceti, an enzyme known as succinyl-CoA:acetate CoA-transferase performs this conversion (PMID: 18502856) while in Helicobacter pylori succinyl-CoA:acetoacetate CoA-transferase is responsible for this reaction (PMID: 9325289). The citric acid cycle is regulated in a number of ways but the primary mechanism is by product inhibition. For instance, NADH inhibits pyruvate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and citrate synthase. Acetyl-CoA inhibits pyruvate dehydrogenase, while succinyl-CoA inhibits alpha-ketoglutarate dehydrogenase and citrate synthase. Additionally, ATP inhibits citrate synthase and alpha-ketoglutarate dehydrogenase. Calcium is another important regulator of the citric acid cycle. In particular, it activates pyruvate dehydrogenase phosphatase, which then activates pyruvate dehydrogenase. Calcium also activates isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase (PMID: 171557).

SMP0121001

Pw122268 View Pathway
Physiological

Kidney Function- Proximal Convoluted Tubule

The proximal convoluted tubule is part of the nephron between the Bowman's capsule and the loop of Henle. The proximal convoluted tubule functions to reabsorb sodium, water, and other ions. Sodium and bicarbonate (hydrogen carbonate) are transported by a co-transporter that is responsible for the majority of sodium reabsorption. The bicarbonate, along with hydrogen, are exchanged across the basal and apical membranes, respectively, to effectively regulate the pH of the filtrate. In addition, chloride ions are not normally reabsorbed in large amounts at the proximal tubule compared to other parts of the nephron. However, the reabsorption of chloride, as well as potassium, increases as the amount of water reabsorption increases due to solvent drag (also known as bulk transport). This occurrence explains solute movement secondary to water flow. All the cation and anion transport creates a gradient favourable for ion and water reabsorption, leading to an increase in blood pressure.

SMP0000012

Pw000017 View Pathway
Metabolic

Catecholamine Biosynthesis

The Catecholamine Biosynthesis pathway depicts the synthesis of catecholamine neurotransmitters. Catecholamines are chemical hormones released from the adrenal glands as a response to stress that activate the sympathetic nervous system. They are composed of a catechol group and are derived from amino acids. The commonly found catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. They are synthesized in catecholaminergic neurons by four enzymes, beginning with tyrosine hydroxylase (TH), which generates L-DOPA from tyrosine. The L-DOPA is then converted to dopamine via aromatic L-amino acid decarboxylase (AADC), which becomes norepinephrine via dopamine beta-hydroxylase (DBH); and finally is converted to epinephrine via phenylethanolamine N-methyltransferase (PNMT).

SMP0000048

Pw000151 View Pathway
Metabolic

Nicotinate and Nicotinamide Metabolism

Nicotinate (niacin) and nicotinamide - more commonly known as vitamin B3 - are precursors of the coenzymes nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+). NAD+ synthesis occurs either de novo from amino acids, or a salvage pathway from nicotinamide. Most organisms use the de novo pathway whereas the savage pathway is only typically found in mammals. The specifics of the de novo pathway varies between organisms, but most begin by forming quinolinic acid (QA) from tryptophan (Trp) in animals, or aspartic acid in some bacteria (intestinal microflora) and plants. Nicotinate-nucleotide pyrophosphorylase converts QA into nicotinic acid mononucleotide (NaMN) by transfering a phosphoribose group. Nicotinamide mononucleotide adenylyltransferase then transfers an adenylate group to form nicotinic acid adenine dinucleotide (NaAD). Lastly, the nicotinic acid group is amidated to form a nicotinamide group, resulting in a molecule of nicotinamide adenine dinucleotide (NAD). Additionally, NAD can be phosphorylated to form NADP. The salvage pathway involves recycling nicotinamide and nicotinamide-containing molecules such as nicotinamide riboside. The precursors are fed into the NAD+ biosynthetic pathwaythrough adenylation and phosphoribosylation reactions. These compounds can be found in the diet, where the mixture of nicotinic acid and nicotinamide are called vitamin B3 or niacin. These compounds are also produced within the body when the nicotinamide group is released from NAD+ in ADP-ribose transfer reactions.

SMP0000053

Pw000024 View Pathway
Metabolic

Folate Metabolism

Folate, or folic acid, is a very important B-vitamin involved in cell creation and preservation, as well as the protection of DNA from mutations that can cause cancer. It is commonly found in leafy green vegetables, but is also present in many other foods such as fruit, dairy products, eggs and meat. Folate is imperative during pregnancy as a deficiency will cause neural tube defects in the offspring. Many countries around the world now fortify foods with folic acid to prevent such defects. This pathway begins in the extracellular space, where folic acid is transported into the cell through a proton-coupled folate transporter. From there, dihydrofolate reductase converts folic acid into dihydrofolic acid. Dihydrofolic acid is then created into tetrahydrofolic acid through dihydrofolate reductase. Tetrahydrofolic acid then sparks the beginning of many reactions and subpathways including purine metabolism and histidine metabolism. There are two reactions that tetrahydrofolic acid undergoes, the first being the catalyzation into tetrahydrofolyl-[glu](2) through the enzyme folylpolyglutamate synthase in the mitochondria. Then, tetrahydrofolyl-[glu](2) becomes tetrahydrofolyl-[glu](n) through folylpolyglutamate synthase. The cycle ends with tetrahydrofolyl-[glu](n) reverting to tetrahydrofolyl-[glu](2) in the lysosome through the enzyme gamma-glutamyl hydrolase. The second reaction that begins with tetrahydrofolic acid sees tetrahydrofolic acid turned into 10-formyltetrahydrofolate through c-1-tetrahydrofolate synthase. This loop is completed by cytosolic 10-formyltetrahydrofolate dehydrogenase reverting 10-formyltetrahydrofolate back to tetrahydrofolic acid. Folate is not stored in the body for very long, as it is a water soluble vitamin and is excreted through urine, so it is important to ingest it continually, as your body’s level of folate will decline after a few weeks if the vitamin is avoided.

SMP0000016

Pw000149 View Pathway
Metabolic

Propanoate Metabolism

This pathway depicts the metabolism of propionic acid. Propionic acid in mammals typically arises from the production of the acid by gut or skin microflora. Propionic acid producing bacteria (Propionibacterium sp.) are particularly common in sweat glands of mammals. After entering a cell, the propionic acid (propanoate) then enters the mitochondria where it is converted into propanol adenylate (or propionyl adenylate or propionyl-AMP) via propionyl-CoA synthetase and acetyl-CoA synthetase. The propionyl adenylate then is converted into propionyl coenzyme A (propionyl-CoA) via the same pair of enzymes. Propionyl-CoA is a relatively common compound that can also arise from the metabolic breakdown of fatty acids containing odd numbers of carbon atoms. Propionyl-CoA is also known to arise from the breakdown of some amino acids. Since propanoate has three carbons, propionyl-CoA cannot directly enter the beta-oxidation cycle (which requires two carbons from acetyl-CoA). Therefore, in most vertebrates, propionyl-CoA is carboxylated into D-methylmalonyl-CoA via propionyl-CoA carboxylase. The resulting compound is isomerized into L-methylmalonyl-CoA via methylmalonyl-CoA epimerase. A vitamin B12-dependent enzyme, called methylmalonyl CoA mutase catalyzes the rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which is an intermediate of the citric acid cycle. Also depicted in this pathway is another propionic acid homolog called hydroxypropanoic acid (hydroxypropionate). This compound is also produced by bacteria and imported into cells. Hydroxypropionate can be converted into 3-hydroxypropionyl-CoA. This compound can be either enzymatically converted to acryloyl-CoA and then to propionyl-CoA or it can spontaneously convert to malonyl-CoA. Malonyl-CoA can convert into acetyl-CoA (via acetyl-CoA carboxylase in the cytoplasm or malonyl carboxylase in the mitochondria) whereupon it may enter a variety of pathways. In a rare genetic metabolic disorder called propionic acidemia, propionate acts as a metabolic toxin in liver cells by accumulating in the liver mitochondria as propionyl-CoA and its derivative methylcitrate. Both propionyl-CoA and methylcitrate are known TCA inhibitors. Glial cells are particularly susceptible to propionyl-CoA accumulation. In fact, when propionate is infused into rat brains and take up by the glial cells, it leads to behavioural changes that resemble autism (PMID: 16950524).
Showing 21 - 30 of 49833 pathways