Browsing Pathways

Cyclopropane fatty acids (CFA) are synthesized by the modification of an unsaturated bond of acyl chains of phospholipid bilayers by methylenation via cyclopropane fatty acyl phospholipid synthase. CFA phospholipid synthase is a unique enzyme in that it acts on the nonpolar part of the phospholipids. The bond that is modified is about nine to eleven carbon atoms from the glycerol backbone. S-adenosyl-L-methionine donates a methylene group to the cis double bond of the unsaturated fatty acid. CFA synthase acts on phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. Cyclopropane fatty acids in the cytoplasmic membrane protect cells from ethanol, high osmotic pressure and other environmental stressors.

Putrescine is an organic chemical produced when amino acids are broken down in organsisms, both living and dead. It can be used as a carbon and nitrogen source in E. coli, and is broken down into gamma-aminobutyric acid (GABA). In this pathway, GABA from putrescine degradation reacts with oxoglutaric acid in a reversible reaction catalyzed by 4-aminobutyrate aminotransferase. This reaction forms succinic acid semialdehyde, as well as L-glutamic acid as a byproduct. Succinic acid semialdehyde is then converted to succinic acid in a reaction catalyzed by succinate-semialdehyde dehydrogenase, using NAD as a cofactor. Succinic acid can then be used by the bacteria in the TCA cycle.

Guanosine can be converted into guanine through a phosphate driven guanosine phosphorylase resulting in the release of an alpha-D-ribose 1 phosphate and a guanine. This compound in turn reacts with a PRPP through a guanine phosphoribosyltransferase resulting in the release of a pyrophosphate and a GMP. Guanosine can also react with and ATP driven guanosine kinase resulting in the release of an ADP, s hydrogen ion and a GMP

Methylglyoxal, also known as pyruvaldehyde, is a cytotoxic compound derived from pyruvic acid. In E. coli, there are at least eight pathways that are responsible for the detoxification of methylglyoxal. The first reaction in this pathway is the reversible reduction of pyruvaldehyde to hydroxyacetone, along with the cofactor NADPH, catalyzed by an uncharacterized protein encoded by the yghZ gene, now known to be L-glyceraldehyde 3-phosphate reductase. Following this, hydroxyacetone is oxidized into (S)-propane-1,2-diol by the glycerol dehydrogenase enzyme, using NAD as a cofactor. Finally, (S)-propane-1,2-diol is transported into the periplasmic space.

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.

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.

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.

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.