Browsing Pathways

L-alanine is an essential component of proteins and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.There are at least 3 ways to begin the biosynthesis of alanine. The first method for alanine biosynthesis begins with L-cysteine produced from L-cysteine biosynthesis pathway. L-cysteine reacts with an [L-cysteine desulfurase] L-cysteine persulfide through a cysteine desulfurase resulting in a release of [L-cysteine desulfurase] l-cysteine persulfide and L-alanine. The second method starts with pyruvic acid reacting with L-glutamic acid through a glutamate-pyruvate aminotransferase resulting in a oxoglutaric acid and L-alanine. The third method starts with L-glutamic acid interacting with Alpha-ketoisovaleric acid through a valine transaminase resulting in an oxoglutaric acid and L-valine. L-valine reacts with pyruvic acid through a valine-pyruvate aminotransferase resulting Alpha-ketoisovaleric acid and L-alanine. This first step of the pathway, which can be catalyzed by either of two racemases (biosynthetic or catabolic), also serves an essential role in biosynthesis because its product, D-alanine, is an essential component of cell wall peptidoglycan (murein). D-alanine is metabolized by an ATP driven D-alanine ligase A and B resulting in D-alanyl-D-alanine. This product is incorporated into the peptidoglycan biosynthesis. L-alanine is metabolized with alanine racemase, either catabolic or metabolic resulting in a D-alanine. This compound reacts with water and a quinone through a D-amino acid dehydrogenase resulting in Pyruvic acid, hydroquinone and ammonium, thus entering the central metabolism and thereby can serve as a total source of carbon and energy. The role of the dadX racemase is degradative and dadX racemase can be induced by alanine and is subject to catabolite repression.

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.

Cytidine and uridine are transported through their corresponding nucleoside hydrogen symporters. Once cytidine is incorporated into the cytosol, it is deaminated through a reaction with water and a hydrogen ion through a cytidine deaminase resulting in the release of ammonium and uridine. Uridine is then lyased by a phosphate through a uridine phosphorylase resulting in the release of a uracil and an alpha-D-ribose-1-phosphate. This compound is then transformed into an isomer D-ribose 5-phosphate through an alpha-D-ribose 1,5-phosphomutase. This compound is then incorporated into the pentose phosphate pathway.

Fructose metabolism begins with the transport of beta-D-glucose 6-phosphate through a glucose PTS permease. This compound is isomerized by a glucose-6-phosphate isomerase resulting in fructose 6-phosphate. This compound can be phosphorylated by two different enzymes: a pyridoxal phosphatase/fructose 1,6-bisphosphatase or an ATP-driven 6-phosphofructokinase-1, resulting in fructose 1,6-biphosphate. This compound can either react with a fructose bisphosphate aldolase class 1 resulting in D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate or through a fructose biphosphate aldolase class 2 resulting in D-glyceraldehyde 3-phosphate. This compound can then either react in a reversible triosephosphate isomerase resulting in dihydroxyacetone phosphate or react with a phosphate through an NAD-dependent glyceraldehyde 3-phosphate dehydrogenase resulting in glyceric acid 1,3-biphosphate. This compound is dephosphorylated by a phosphoglycerate kinase resulting in 3-phosphoglyceric acid. This compound, in turn, can either react with a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase or a 2,3-bisphosphoglycerate-independent phosphoglycerate mutase resulting in 2-phospho-D-glyceric acid. This compound interacts with an enolase resulting in a phosphoenolpyruvic acid and water. Phosphoenolpyruvic acid can react either through an AMP-driven phosphoenoylpyruvate synthase or an ADP-driven pyruvate kinase protein complex resulting in pyruvic acid. The pyruvic acid reacts with CoA through an NAD-driven pyruvate dehydrogenase complex resulting in carbon dioxide and an acetyl-CoA which gets incorporated into the TCA cycle pathway.

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.

Purine ribonucleoside degradation leads to the production of alpha-D-ribose-1-phosphate. Xanthosine is transported into the cytosol through a xapB. Once in the cytosol xanthosine interacts with phosphate through a xanthosine phosphorylase resulting in the release of a xanthine and a alpha-D-ribose-1-phosphate. Adenosine is transported through a nupC or a nupG transporter, once inside the cytosol it can either react with a phosphate through a adenosine phosphorylase resultin in the release of a adenine and an alpha-D-ribose-1-phosphate. Adenosine reacts with water and hydrogen ion through a adenosine deaminase resulting in the release of ammonium and inosine. Inosine reacts with phosphate through a inosine phosphorylase resulting in the release of a hypoxanthine and an alpha-D-ribose-1-phosphate. Guanosine reacts with a phosphate through a guanosine phosphorylase resulting in the release of a guanine and a alpha-D-ribose-1-phosphate.

Lipopolysaccharide (LPS) is a major component of outer membrane which is consisted of lipid A-core (oligosaccharide) on both inner and outer region and O-antigen (known as distal repeating unit with four sugars: N-acetylglucosamine, glucose, rhamnose and galactose). O-antigen is part of three domains of LPS, which is attached to lipid A-core; however, O-antigen and lipid A-core are synthesized separately. In this pathway, synthesis of three of O-antigen sugars is demonstrated. UDP-α-D-galactose is converted to UDP-D-Galacto-1,4-furanose by facilitation of UDP-galactopyranose mutase. dTTP glucose-1-phosphate is derivatized to dTDP-rhamnose. Fructose-6-phosphate gains an amino group, incorporates an acetate moiety and then acquires a nucleoside diphosphate resulting in UDP-N-acetyl-D-glucosamine.

Lipopolysaccharide (LPS) is a major component of outer membrane which is consisted of lipid A-core (oligosaccharide) on both inner and outer region and O-antigen (known as distal repeating unit with four sugars: N-acetylglucosamine, glucose, rhamnose and galactose). O-antigen is part of three domains of LPS, which is attached to lipid A-core; however, O-antigen and lipid A-core are synthesized separately. In this pathway, synthesis of three of O-antigen sugars is demonstrated. UDP-α-D-galactose is converted to UDP-D-Galacto-1,4-furanose by facilitation of UDP-galactopyranose mutase. dTTP glucose-1-phosphate is derivatized to dTDP-rhamnose. Fructose-6-phosphate gains an amino group, incorporates an acetate moiety and then acquires a nucleoside diphosphate resulting in UDP-N-acetyl-D-glucosamine.

This pathway demonstrate the biosynthesis of thiazole moiety in E.coli K-12 strain and Salmonella enterica serovar Typhimurium. L-Tyrosine is generated from tyrosine biosynthesis. With S-Adenosylmethionine and NADPH, L-Tyrosine can be catalyzed into four different small molecules: 4-methylcatechol, dehydroglycine, 5'-deoxyadenosine and L-methionine as well as NADP by dehydroglycine synthase (encoded by thiH gene). Meanwhile, 1-deoxyxylulose-5-phosphate synthase (encoded by dxs gene) catalyzes pyruvic acid and D-Glyceraldehyde 3-phosphate into 1-Deoxy-D-xylulose 5-phosphate. The final reaction of the pathway is facilitated by thiazole synthase (encoded by thiG and thiH), which require a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate to form 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate for Thiamin Diphosphate Biosynthesis, as well as a ThiS sulfur-carrier protein and water.