Browsing Pathways

L-threonine is degrade into methylglyoxal (pyruvaldehyde) by first reacting with a NDA dependent threonine dehydrogenase resulting in the release of a hydrogen ion, an NADH and a 2-amino-3-oxobutanoate. The latter compound reacts spontaneously with a hydrogen ion resulting in the release of a carbon dioxide and a aminoacetone. The aminoacetone in turn reacts with an oxygen and a water molecule through an aminoacetone oxidase resulting in the release of a hydrogen peroxide, ammonium and a methylglyoxal which can then be incorporated in the methylglyoxal degradation pathways.

Fatty acid oxidation is also known as beta-oxidation. Fatty acids are an important energy source because they are anhydrous and can be reduced. Fatty acids are good sources of energy as they yield more energy than carbohydrates. The fatty acid oxidation pathway degrades fatty acids into acetyl-CoA under anaerobic and aerobic conditions. Enzymes of this pathway can process short and long chain fatty acids. The first step in the pathway is the conversion of acyl-CoA to enoyl-CoA. The pathway continues in a cycle, each turn removing two carbon atoms from the input acyl-CoA to produce acetyl-CoA. Each turn also produces NADH.

Fatty acid oxidation is also known as beta-oxidation. Fatty acids are an important energy source because they are anhydrous and can be reduced. Fatty acids are good sources of energy as they yield more energy than carbohydrates. The fatty acid oxidation pathway degrades fatty acids into acetyl-CoA under anaerobic and aerobic conditions. Enzymes of this pathway can process short and long chain fatty acids. The first step in the pathway is the conversion of acyl-CoA to enoyl-CoA. The pathway continues in a cycle, each turn removing two carbon atoms from the input acyl-CoA to produce acetyl-CoA. Each turn also produces NADH.

Fatty acid oxidation is also known as beta-oxidation. Fatty acids are an important energy source because they are anhydrous and can be reduced. Fatty acids are good sources of energy as they yield more energy than carbohydrates. The fatty acid oxidation pathway degrades fatty acids into acetyl-CoA under anaerobic and aerobic conditions. Enzymes of this pathway can process short and long chain fatty acids. The first step in the pathway is the conversion of acyl-CoA to enoyl-CoA. The pathway continues in a cycle, each turn removing two carbon atoms from the input acyl-CoA to produce acetyl-CoA. Each turn also produces NADH.

Fatty acid oxidation is also known as beta-oxidation. Fatty acids are an important energy source because they are anhydrous and can be reduced. Fatty acids are good sources of energy as they yield more energy than carbohydrates. The fatty acid oxidation pathway degrades fatty acids into acetyl-CoA under anaerobic and aerobic conditions. Enzymes of this pathway can process short and long chain fatty acids. The first step in the pathway is the conversion of acyl-CoA to enoyl-CoA. The pathway continues in a cycle, each turn removing two carbon atoms from the input acyl-CoA to produce acetyl-CoA. Each turn also produces NADH.

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.

Trehalose is a disaccharide made of two glucose molecules that can be used as a store of energy, as well as water retention and protection from freezing at low temperatures. In this pathway, glucose-6-phosphate from the galactose metabolism pathway combines with uridine diphosphate glucose to form alpha,alpha-trehalose 6-phosphate, as well as uridine 5’-diphosphate and a hydrogen ion as byroducts in a reaction catalyzed by alpha,alpha-trehalose-phosphate synthase [UDP-forming]. Following this, alpha,alpha-trehalose 6-phosphate is converted to alpha,alpha-trehalose following the hydrolytic cleavage of its phosphate group by trehalose-phosphate phosphatase. Alpha,alpha-trehalose can then function as energy stores until it is broken down as a part of the trehalose degradation pathway when needed.

Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space. The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine.

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.