Browsing Pathways

Aminopropylcadaverine, a polyamine, is the final product of aminopropylcadaverine biosynthesis pathway. Polyamines are involved in protein synthesis, DNA and RNA related processes, as well as the facilitation of cell stress resistance and membrane integrity; therefore polyamines are essential for cell growth. In this pathway, L-lysine is produced by lysine biosynthesis, then lysine decarboxylase will convert L-lysine into cadaverine. In the final step, spermidine synthase will catalyze cadaverine and decarboxy-SAM to aminopropylcadaverine as well as 5'-Methylthioadenosine.

The biosynthesis of Valine and L-leucine from pyruvic acid starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase resulting in a release of a carbon dioxide, a (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through a NADPH-driven acetohydroxy acid isomeroreductase resulting in the release of a NADP, a (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of a water molecule an 3-methyl-2-oxovaleric acid. The 3-methyl-2-oxovaleric acid can produce an L-valine by interacting with a L-glutamic acid through a Valine Transaminase resulting in the release of a Oxoglutaric acid and a L-valine. The 3-methyl-2-oxovaleric acid then interacts with an acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in the release of a hydrogen ion, a Coenzyme A and a 2-Isopropylmalic acid. The isopropylimalic acid is then hydrated by interacting with a isopropylmalate isomerase resulting in a 3-isopropylmalate. This compound then interacts with an NAD driven 3-isopropylmalate dehydrogenase resulting in a NADH, a hydrogen ion and a 2-isopropyl-3-oxosuccinate. The latter compound then interacts with hydrogen ion spontaneously resulting in a carbon dioxide and a ketoleucine. The ketoleucine then interacts with a L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in the oxoglutaric acid and L-leucine.

The citric acid cycle (also named tricarboxylic acid (TCA) cycle or the Krebs cycle), is a collection of 9 enzyme-catalyzed chemical reactions that occur in all living cells undergoing aerobic respiration. The citric acid cycle itself was officially identified in 1937 by Hans Adolf Krebs, who received the Nobel Prize for this discovery in 1953. In eukaryotes, the citric acid cycle occurs in the mitochondria. In prokaryotes, the TCA cycle occurs in the cytoplasm. The TCA cycle starts with acetyl-CoA, which is the “fuel” for the entire cycle. This important molecule comes from the breakdown of glycogen (a stored form of glucose), fats, and many amino acids. At beginning, acetyl-CoA first transfers its 2-carbon acetyl group to the 4-carbon acceptor compound called oxaloacetate to form the 6-carbon compound (citrate) for which the cycle is named. The resulting citrate will have numbers of chemical transformations, whereby it loses one carboxyl group (leading to the 5-carbon compound called alpha-ketoglutarate) and then a second carboxyl group (leading to the 4-carbon compound called succinate). Succinate molecule is further oxidized to fumarate, then malate and finally oxaloacetate. The regeneration of the 4-carbon oxaloacetate, allows the TCA cycle to continue. Oxidation step generates energy that is transferring energy-rich electrons for NAD+ to form NADH in TCA cycle. Each acetyl group will generate 3 NADH in TCA cycle.

The citric acid cycle (also named tricarboxylic acid (TCA) cycle or the Krebs cycle), is a collection of 9 enzyme-catalyzed chemical reactions that occur in all living cells undergoing aerobic respiration. The citric acid cycle itself was officially identified in 1937 by Hans Adolf Krebs, who received the Nobel Prize for this discovery in 1953. In eukaryotes, the citric acid cycle occurs in the mitochondria. In prokaryotes, the TCA cycle occurs in the cytoplasm. The TCA cycle starts with acetyl-CoA, which is the “fuel” for the entire cycle. This important molecule comes from the breakdown of glycogen (a stored form of glucose), fats, and many amino acids. At beginning, acetyl-CoA first transfers its 2-carbon acetyl group to the 4-carbon acceptor compound called oxaloacetate to form the 6-carbon compound (citrate) for which the cycle is named. The resulting citrate will have numbers of chemical transformations, whereby it loses one carboxyl group (leading to the 5-carbon compound called alpha-ketoglutarate) and then a second carboxyl group (leading to the 4-carbon compound called succinate). Succinate molecule is further oxidized to fumarate, then malate and finally oxaloacetate. The regeneration of the 4-carbon oxaloacetate, allows the TCA cycle to continue. Oxidation step generates energy that is transferring energy-rich electrons for NAD+ to form NADH in TCA cycle. Each acetyl group will generate 3 NADH in TCA cycle.

Threhalose biosynthesis begins with an Alpha-D-glucose-1-phosphate interacting with an ATP through a glucose-1-phosphate adenylyltransferase resulting in the release of a pyrophosphate and an ADP-glucose. The latter compound interacts in a reversible reaction with an amylose through a glycogen synthase resulting in the release of an ADP and an amylose. Amylose then interacts in a reversible reaction with 1,4-α-glucan branching enzyme resulting in a glycogen Glycogen can also be produced by a reversible reaction with Amylose through a maltodextrin phosphorylase, releasing a phosphate and a glycogen. Glycogen is then transformed into trehalose through a glycogen debranching enzyme. Alpha Alpha Trehalose can be degraded by reacting with with a water molecule through a cytoplasmic trehalase resulting in the release of a Beta-D-glucose and an Alpha-D-glucose.phosphorylated resulting in a Beta-D-glucose 6-phosphate. This compound is phosphorylated and can then join glycolysis Alpha Alpha Trehalose can be degraded in the periplasmic space by reacting with with a water molecule through a periplasmic trehalase resulting in the release of a Beta-D-glucose and an Alpha-D-glucose. The beta-D-glucose can be transported into the cytosol through a PTS permease where it is phosphorylated resulting in a Beta-D-glucose 6-phosphate. This compound can then join glycolysis

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.

Taurine is incorporated into the cytoplasm through a taurine ABC transporter. Once inside the cytoplasm, taurine interacts with an oxoglutaric acid and an oxygen through a taurine dioxygenase resulting in the release of succinic acid, sulfite , aminoacetaldehyde and carbon dioxide.

The S-adenosyl-L-methionine cycle starts with S-adenosyl-L-methionine reacting with (a demethylated methyl donor ) dimethylglycine resulting in the release of a hydrogen ion, a betain (a methylated methyl donor) and a S-adenosyl-L-homocysteine. The s-adenosyl-L-homocysteine reacts with a water molecule through a S-adenosylhomocysteine nucleosidase resulting in the release of a adenine and a ribosyl-L-homocysteine. This compound in turn reacts with a s-ribosylhomocysteine lyase resulting in the release of a l-homocysteine and a autoinducer 2. The L-homocysteine reacts with a N5-methyl-tetrahydropteroyl tri-L-glutamate through a methionine synthase resulting in the release of a tetrahydropteroyl tri-L-glutamate and a methione. The methionine in turn reacts with a water molecule and ATP molecule through a methionine adenosyltransferase resulting in the release of a diphosphate, a phosphate and a s-adenosyl-L-methionine.

ADP-L-glycero-β-D-manno-heptose is a precursor for the inner core lipopolysaccharide (LPS), which is the outer membrane of Gram-negative bacteria. LPS is consisted of lipid A, a core oligosaccharide, and an O-specific polysaccharide (O antigen). This biosynthesis pathway starts with catalyzation of D-sedoheptulose 7-phosphate that produced from pentose phosphate pathway to form D-glycero-D-manno-heptose 7-phosphate by lysophospholipid acyltransferase. D-glycero-D-manno-heptose 7-phosphate later undergoes catalyze to form D-glycero-β-D-manno-heptose 1,7-bisphosphate by fused heptose 7-phosphate kinase (also known as heptose 1-phosphate adenyltransferase) that powered by ATP. D-glycero-β-D-manno-heptose 1,7-bisphosphate will go through hydrolysis by D,D-heptose 1,7-bisphosphate phosphatase to form D-glycero-β-D-manno-heptose 1-phosphate and a phosphate. D-glycero-β-D-manno-heptose 1-phosphate will form ADP-D-Glycero-D-manno-heptose and diphosphate, and eventually ADP-D-Glycero-D-manno-heptose will be biotransformed to ADP-L-glycero-β-D-manno-heptose as the end product of this pathway by ADP-L-glycero-D-mannoheptose-6-epimerase.

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.