Browsing Pathways

Urea, also known as carbamide, is a waste product made by a large variety of living organisms and is the main component of urine. Urea is created in the liver, through a string of reactions that are called the Urea Cycle. This cycle is also called the Ornithine Cycle, as well as the Krebs-Henseleit Cycle. There are some essential compounds required for the completion of this cycle, such as arginine, citrulline and ornithine. Arginine cleaves and creates urea and ornithine, and the reactions that follow see urea residue build up on ornithine, which recreates arginine and keeps the cycle going. Ornithine is transported to the mitochondrial matrix, and once there, ornithine carbamoyltransferase uses carbamoyl phosphate to create citrulline. After this, citrulline is transported to the cytosol. Once here, citrulline and aspartate team up to create argininosuccinic acid. After this, argininosuccinate lyase creates l-arginine. L-arginine finally uses arginase-1 to create ornithine again, which will be transported to the mitochondrial matrix and restart the urea cycle once more.

The biosynthesis of fatty acids primarily occurs in liver and lactating mammary glands. The entire synthesis process which produces palmitic acid occurs on a multifunctional dimeric protein Fatty Acid Synthase (FA) in the cytosol. The production of palmitic acid can be summarized as the successive addition of two carbons to an initial acetyl moiety primer. After 7 cycles palimitic acid is released. The synthesis starts with the sequential transfer of a primer substrate, acetyl-CoA, to the nucleophilic serine residue of the acyltransferase domain of FA. The acetyl moiety is then transferred to the Acyl Carrier Protein (ACP) domain of FA, then finally to the active site of the beta-ketoacyl synthase domain. A chain extender substrate, molonyl-CoA, is transferred to the nucleophilic serine residue of the acyltransferase domain and subsequently to the ACP domain. The acetyl moiety is extend by a condensation reaction, catalysed by the beta-ketoacyl synthase domain, that produces a new Carbon-Carbon bound, this reaction is coupled to a decarboxylation resulting in the production of carbon dioxide. Subsequently beta-ketoacyl condensation product is reduced to a saturated acyl moiety through the step wise action on the beta-ketoacyl reductase, beta-hydroxyacyl dehydrase and enoyl reductase domains respectively. This saturated acyl moiety is then transfer back to the active site of the beta-ketoacyl synthase domain, another molonyl-CoA is loaded and the process repeats. The addition of molonyl moieties occurs 7 times after which the final product is released by that action of thioesterase domain. The final product is 16 carbon long palmitic acid.

Thio-molybdenum cofactor biosynthesis is a pathway that begins in the mitochondrial matrix and ends in the cytosol by which GTP becomes thio-molybdenum cofactor, the sulfo-form of molybdenum cofactor required by certain plant enzymes. First, the enzyme GTP 3',8-cyclase, located in the mitochondrial matrix, catalyzes the conversion of GTP, S-adenosylmethionine, and a reduced electron acceptor to 3′,8-cH2GTP, L-methionine, 5'-deoxyadenosine, an oxidized electron acceptor, and a hydrogen ion with the help of a [4Fe-4S] cluster cofactor. Second, cyclic pyranopterin monophosphate (cPMP) synthase catalyzes the conversion of 3′,8-cH2GTP to cPMP and pyrophosphate. Next, ABC transporter of the mitochondrion 3 (ATM3) exports cPMP from the mitochondrial matrix into the cytosol where it is acted upon by molybdopterin (MPT) synthase. MPT synthase is a heterotetramer composed of 2 large and 2 small subunits. The two small subunits are thiocarboxylated by molydopterin synthase sulfurtransferase, and each transfers a sulfur to cPMP to generate the dithiolene in molybdopterin and releasing hydrogen ion in the process. The following enzyme in the pathway, molybdenum insertase is a two-domain protein that catalyzes the fourth and fifth reactions. The smaller C-terminal Cnx1G domain functions as a molybdopterin molybdotransferase and activates molybdopterin for molybdenum insertion. The product of this reaction, molybdopterin adenine dinucleotide (MPT-AMP), is then transferred to the larger N-terminal Cnx1E domain which exhibits molybdopterin adenylyltransferase activity and inserts molybdenum into the dithiolene of molybdopterin, creating molybdenum cofactor (Moco). Molybdenum insertase requires a divalent cation (e.g. magnesium) as a cofactor. Lastly, molybdenum cofactor sulfurtransferase uses L-cysteine and a reduced electron acceptor to convert molybdenum cofactor into thio-molybdenum cofactor, producing L-alanine, oxidized electron acceptor, and water as byproducts. It requires pyridoxal 5'-phosphate as a cofactor.

Choline is a nitrogen-containing, water-soluble nutrient that is incorporated into the headgroups of membrane phospholipids such as phosphatidylcholine. Two pathways exist for choline biosynthesis whereby serine becomes choline. Both of these pathways take place in the cytosol. This is the first pathway of choline biosynthesis. First, serine decarboxylase (SDC) uses a proton and a pyridoxal 5'-phosphate cofactor to catalyze the conversion of L-serine to ethanolamine, producing carbon dioxide as a byproduct. Second, ethanolamine kinase, localized to the cell membrane (coloured dark green in the image), uses ATP to catalyze the conversion of ethanolamine to O-phosphoethanolamine. Note that this is only the probable ethanolamine kinase in Arabidopsis thaliana and requires further research to confirm its function. Steps 3, 4, and 5 are catalyzed by phosphoethanolamine N-methyltransferase (PEAMT). These three sequential N-methylation steps convert phosphoethanolamine to phosphocholine and utilize S-adenosyl-L-methionine as a methyl donor. The intermediates are as follows: O-Phosphoethanolamine, N-methylethanolamine phosphate, and N-dimethylethanolamine phosphate. Sixth, phosphoethanolamine/phosphocholine phosphatase catalyzes the synthesis of choline from phosphocholine. It requires magnesium as a cofactor.

Purine nucleotides are eventually degraded to ammonia and carbon dioxide. This pathway follows the degradation of AMP to a urate intermediate in the cytosol via xanthine conversion from hypoxanthine. First, AMP deaminase catalyzes the conversion of AMP is into IMP. Second, the predicted enzyme 5′-nucleotidase (coloured orange in the image) is theorized to convert IMP into inosine. Third, ribonucleoside hydrolase converts inosine into hypoxanthine. Fourth, xanthine dehydrogenase is an enzyme that requires [2Fe-2S] cluster, FAD, and Moco as cofactors for catalyzing two subsequent reaction in the AMP degradation pathway: the conversion of hypoxanthine into xanthine and the conversion of xanthine into urate.

Abscisic acid glucose ester metabolism is a pathway that begins in the chloroplast and enters the cytosol and endoplasmic reticulum body by which violaxanthin becomes abscisic acid glucose ester, synthesizing abscisic acid in the process. Abscisic acid glucose ester synthesis and reformation back to abscisic acid provides a mechanism for precisely controlling abscisic acid concentration (quickly removing and adding abscisic acid when required). First, neoxanthin synthase catalyzes the opening of the violaxanthin epoxide ring to form neoxanthin. Second, a yet unidentified neoxanthin isomerase is theorized to isomerize neoxanthin to 9'-cis-neoxanthin. Third, 9-cis-epoxycarotenoid dioxygenase (NCED) uses oxygen to cleave 9'-cis-neoxanthin to form xanthoxin and C25-allenic-apo-aldehyde. This enzyme requires Fe2+ as a cofactor. Next, a xanthoxin transporter is theorized to export xanthoxin from the chloroplast into the cytosol to continue abscisic acid biosynthesis, but it has yet to be discovered. Fourth, xanthoxin dehydrogenase, located in the cytosol, catalyzes the conversion of xanthoxin and NAD to abscisic aldehyde, NADH, and a proton with the help of a molybdenum cofactor (MoCo). Fifth, abscisic-aldehyde oxidase converts abscisic aldehyde, water, and oxygen into hydrogen peroxide, hydrogen ion, and abscisic acid. Sixth, abscisic acid glucosyltransferase uses UDP to convert abscisic acid into abscisic acid glucose ester. Abscisic acid glucose ester can then be converted back to abscisic acid via abscisic acid glucose ester beta-glucosidase located in the endoplasmic reticulum body (coloured dark green in the image). Consequently, it is theorized that ABA-GE transporters are required for this enzyme to access its substrates from the cytosol.

The Leloir pathway is a metabolic pathway for the catabolism of D-galactose into D-glucopyranose 6-phosphate named after Luis Federico Leloir . Since galactose cannot be directly used for glycolysis, it needs to be converted into a different form. This pathway starts in the cytosol and finishes in the chloroplast. First, aldose 1-epimerase is a predicted enzyme (coloured orange in the image) that is theorized to catalyze the conversion of beta-D-galactose into alpha-D-galactose. This enzyme has not yet been elucidated for Arabidopsis thaliana. Second, galactokinase catalyzes the conversion of alpha-D-galactose into alpha-D-galactose 1-phosphate. Third, D-galactose-1-phosphate uridylyltransferase is a predicted enzyme theorized to catalyze the reaction whereby alpha-D-galactose 1-phosphate and UDP-glucose is converted into alpha-D-glucopyranose 1-phosphate and UDP-galactose. This enzyme has not yet been elucidated in Arabidopsis thaliana. UDP-glucose and UDP-galactose can be interconverted by the enzyme UDP-glucose 4-epimerase which requires NAD as a cofactor. Alpha-D-glucopyranose 1-phosphate must then be imported into the chloroplast, by a yet not discovered alpha-D-glucopyranose 1-phosphate transporter. Last, phosphoglucomutase uses magnesium ion as a cofactor to convert alpha-D-glucopyranose 1-phosphate into D-glucopyranose 6-phosphate.

Chlorophyll a is the primary form of chlorophyll in plants. Chlorophylls are pigments that give plants their perceived green colour and are essential for photosynthesis, the process by which light energy is converted into chemical energy. Chlorophyll a, in particular, absorbs energy from wavelengths of violet-blue and orange-red light. Two pathways exist for chlorophyll a biosynthesis whereby geranylgeranyl diphosphate and 3,8-divinyl chlorophyllide a becomes chlorophyll a. Both of these pathways take place in the chloroplast. This is the second pathway of chlorophyll a biosynthesis. First, 3,8-divinyl protochlorophyllide a 8-vinyl-reductase converts 3,8-divinyl chlorophyllide into chlorophyllide a. Second, chlorophyll synthetase uses magnesium ion as a cofactor to convert chlorophyllide a and geranylgeranyl diphosphate into geranylgeranyl chlorophyll a. The next three reactions to synthesize chlorophyll a from geranylgeranyl chlorophyll a are catalyzed by the same enzyme, geranylgeranyl dehydrogenase. It converts geranylgeranyl chlorophyll a into dihydrogeranylgeranyl chlorophyll a, dihydrogeranylgeranyl chlorophyll a into tetrahydrogeranylgeranyl chlorophyll a, and tetrahydrogeranylgeranyl chlorophyll a into chlorophyll a.

In higher plants, the primary seed storage reserve is triacylglycerol rather than carbohydrates. Thus, triacylglycerol degradation is an important pathway from which plants obtain energy for growth. First, triacylglycerol lipase, an enzyme localized to the oil body (storage vacuole) membrane, catalyzes the conversion of a triglyceride into a 1,2-diglyceride. Second, the predicted enzyme diglyceride lipase (coloured orange in the image) is theorized to catalyze the conversion of a 1,2-diglyceride iinto a 2-acylglycerol. Third, a 2-acylglycerol is spontaneously converted into a 1-monoglyceride. Fourth, acylhydrolase catalyzes the conversion of a 1-monoglyceride into glycerol. Fifth, glycerol kinase catalyzes the conversion of glycerol into glycerol 3-phosphate. Sixth, glycerol-3-phosphate dehydrogenase (coloured dark green in the image), localized to the mitochondrial inner membrane, catalyzes the conversion of glycerol 3-phosphate into glycerone phosphate.

CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo) biosynthesis is a pathway that occurs in the cytosol by which D-ribulose 5-phosphate becomes CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo). Kdo is a component in the plant cell wall, specifically of pectic polysaccharide rhamnogalacturonan II. First, arabinose-5-phosphate isomerase catalyzes the conversion of D-ribulose 5-phosphate to D-arabinose 5-phosphate. Second, D-arabinose 5-phosphate is spontaneously converted into D-arabinofuranose 5-phosphate. Third, 3-deoxy-8-phosphooctulonate synthase converts D-arabinofuranose 5-phosphate into 3-deoxy-D-manno-octulosonate 8-phosphate (KDO-8P). This enzme is a homotetramer. Fourth, the predicted enzyme 3-deoxy-manno-octulosonate-8-phosphatase (coloured orange in the image) is theorized to catalyze the conversion of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO-8P) into 3-deoxy-D-manno-2-octulosonate (Kdo). The last reaction is localized to the mitochondria outer membrane whereby 3-deoxy-manno-octulosonate cytidylyltransferase (coloured dark green in the image) catalyzes the conversion of 3-deoxy-D-manno-2-octulosonate (Kdo) into CMP-3-deoxy-D-manno-octulosonate (CMP-Kdo). This enzyme requires a magnesium ion as a cofactor.