Browsing Pathways

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.

Aminoacyl-tRNA biosynthesis is an essential process in bacteria that ensures accurate translation of genetic information into functional proteins. This pathway involves the attachment of specific amino acids to their corresponding transfer RNAs (tRNAs) by enzymes known as aminoacyl-tRNA synthetases. Each synthetase is highly specific, recognizing both the correct amino acid and its matching tRNA, ensuring fidelity in protein synthesis. The process begins with the activation of an amino acid by ATP, forming an aminoacyl-AMP intermediate. The activated amino acid is then transferred to the 3' hydroxyl group of the corresponding tRNA, forming an aminoacyl-tRNA. This charged tRNA is delivered to the ribosome during translation, where it pairs with the appropriate codon on the mRNA, ensuring the incorporation of the correct amino acid into the growing polypeptide chain. This biosynthesis pathway is critical for bacterial survival and growth, as it directly links nucleotide sequences to functional proteins. Targeting aminoacyl-tRNA synthetases has been explored in antibiotic development, as disrupting this process can halt protein synthesis and bacterial replication.

Riboflavin (vitamin B2) metabolism in bacteria encompasses both its biosynthesis and utilization as a precursor for cofactors such as flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential for numerous redox reactions. Many bacteria synthesize riboflavin de novo via a conserved pathway starting from guanosine triphosphate (GTP) and ribulose-5-phosphate. The pathway involves key enzymes like GTP cyclohydrolase II, which converts GTP to formate and 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone-5′-phosphate, followed by further modifications to form riboflavin. Once synthesized or acquired from the environment, riboflavin is phosphorylated by riboflavin kinase to produce FMN, which can subsequently be converted into FAD by FAD synthetase. These flavin cofactors play crucial roles in bacterial metabolism, including energy production in the electron transport chain, fatty acid β-oxidation, and oxidative stress responses. Some bacteria, particularly pathogens, rely on riboflavin uptake from their host via specific riboflavin transporters, making the metabolism and acquisition of riboflavin a potential target for novel antibacterial therapies. This pathway is not only vital for bacterial survival but also contributes to the ecological nutrient cycles through flavin biosynthesis and degradation.

Crassulacean Acid Metabolism (CAM) is a specialized photosynthetic pathway predominantly observed in plants, but certain cyanobacteria exhibit similar metabolic adaptations to optimize carbon fixation under fluctuating environmental conditions. CAM operates in two phases: the dark phase and the light phase, allowing organisms to conserve water and improve carbon efficiency. During the dark phase, CO₂ is taken up and fixed into organic acids, such as malate, which are stored in vacuole-like structures or cytoplasmic pools. This is facilitated by the enzyme phosphoenolpyruvate carboxylase (PEPC). In the light phase, the stored organic acids are decarboxylated to release CO₂, which is then refixed by the Calvin-Benson cycle in the presence of light-driven ATP and NADPH generation via photosynthesis. This temporal separation of CO₂ uptake and utilization allows CAM-adapted cyanobacteria to thrive in environments with limited water availability or high salinity, where daytime stomatal opening (or equivalent carbon uptake processes) would lead to excessive water loss. While CAM-like pathways in bacteria are less well understood compared to plants, they represent an important ecological adaptation for survival in extreme habitats.

N-hexanoyl-L-homoserine lactone (C6-HSL) is a quorum sensing signaling molecule produced by certain Gram-negative bacteria, including species of Vibrio and Pseudomonas. This molecule enables bacterial populations to communicate and coordinate behaviors such as biofilm formation, virulence, and motility. The biosynthesis of C6-HSL is catalyzed by an acyl-homoserine lactone synthase enzyme, such as LuxI or its homologs. The process begins with L-homoserine, which serves as the backbone for the molecule. A fatty acyl group, specifically a hexanoyl group derived from hexanoyl-CoA, is transferred to L-homoserine by the synthase enzyme, forming an amide bond. This intermediate is then cyclized to produce C6-HSL. Additionally, during this process, N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) is also produced, which results from the modification of the hexanoyl group by the addition of a keto group at the C-3 position, catalyzed by some LuxI homologs that incorporate a 3-oxo group into the acyl chain. Both C6-HSL and 3-oxo-C6-HSL are quorum sensing molecules that diffuse out of the bacterial cell into the surrounding environment. As the bacterial population grows, the concentration of these signaling molecules increases. When they reach a critical threshold, they bind to a receptor protein such as LuxR, forming a C6-HSL-LuxR or 3-oxo-C6-HSL-LuxR complex that activates the transcription of quorum sensing-regulated genes. This system enables bacteria to synchronize their actions in response to population density, influencing processes such as pathogenicity, surface colonization, and resource utilization.

Pyridoxal phosphate (Pyridoxal-P or PLP) biosynthesis is a vital metabolic pathway in bacteria, as PLP is the active form of vitamin B6 and serves as a coenzyme in a wide range of enzymatic reactions, including amino acid metabolism, neurotransmitter synthesis, and nucleic acid metabolism. The biosynthesis of PLP typically occurs via the de novo pathway, involving two key enzymes: PdxA and PdxJ. This pathway begins with precursors such as ribose-5-phosphate (from the pentose phosphate pathway), glyceraldehyde-3-phosphate, and glutamine or glutamate, depending on the bacterial species. PdxA and PdxJ catalyze the sequential conversion of these precursors into pyridoxine 5'-phosphate (PNP), which is then oxidized by PdxH (a pyridoxine 5'-phosphate oxidase) to form PLP. This highly conserved pathway ensures that bacteria can synthesize PLP even in the absence of external vitamin B6 sources, making it crucial for survival and growth. Additionally, PLP biosynthesis is a potential target for antimicrobial drugs, as disrupting this pathway impairs bacterial metabolism and viability.

N-butanoyl-L-homoserine lactone (C4-HSL) is a signaling molecule involved in quorum sensing in certain Gram-negative bacteria, particularly Pseudomonas species. C4-HSL is synthesized through a pathway that begins with the precursor L-homoserine. The enzyme ButM, which is part of the N-acylhomoserine lactone (AHL) synthase family, catalyzes the conversion of L-homoserine into N-butanoyl-L-homoserine lactone by attaching a butanoyl group to the amino group of homoserine. This reaction requires butyryl-CoA as the donor of the butanoyl group, facilitating the production of C4-HSL. C4-HSL is secreted by the bacteria and can accumulate in the extracellular environment as the population density increases. Once a threshold concentration of C4-HSL is reached, it binds to specific transcriptional regulators like LasR in Pseudomonas aeruginosa, activating the expression of genes involved in biofilm formation, virulence, and antibiotic resistance. The biosynthesis of C4-HSL is an essential component of bacterial communication, allowing the bacteria to coordinate collective behaviors and adapt to changing environmental conditions. This pathway exemplifies how bacteria use small molecules like C4-HSL to regulate gene expression and engage in cooperative actions that enhance their survival and pathogenicity.

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.