Pathways

Phosphatidylethanolamines (PE) are a class of phospholipids that incorporate a phosphoric acid headgroup into a diacylglycerol backbone. They are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In the visualization, all enzymes that are dark green in colour are membrane-localized. The first pathway synthesizes phosphatidylethanolamine from ethanolamine via the Kennedy pathway. First, the cytosol-localized enzyme choline/ethanolamine kinase catalyzes the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Phosphatidylethanolamine is also synthesized from phosphatidylserine at the mitochondrial inner membrane by phosphatidylserine decarboxylase. Phosphatidylserine, itself, is synthesized using a base-exchange reaction with phosphatidylcholine. This reaction is catalyzed by phosphatidylserine synthase which is located in the endoplasmic reticulum membrane.

Phosphatidylethanolamines (PE) are a class of phospholipids that incorporate a phosphoric acid headgroup into a diacylglycerol backbone. They are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In the visualization, all enzymes that are dark green in colour are membrane-localized. The first pathway synthesizes phosphatidylethanolamine from ethanolamine via the Kennedy pathway. First, the cytosol-localized enzyme choline/ethanolamine kinase catalyzes the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Phosphatidylethanolamine is also synthesized from phosphatidylserine at the mitochondrial inner membrane by phosphatidylserine decarboxylase. Phosphatidylserine, itself, is synthesized using a base-exchange reaction with phosphatidylcholine. This reaction is catalyzed by phosphatidylserine synthase which is located in the endoplasmic reticulum membrane.

Phosphatidylethanolamines (PE) are a class of phospholipids that incorporate a phosphoric acid headgroup into a diacylglycerol backbone. They are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In Homo sapiens, there exist two phosphatidylethanolamine biosynthesis pathways. In the visualization, all enzymes that are dark green in colour are membrane-localized. The first pathway synthesizes phosphatidylethanolamine from ethanolamine via the Kennedy pathway. First, the cytosol-localized enzyme choline/ethanolamine kinase catalyzes the conversion of choline into phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes the conversion of phosphocholine to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Phosphatidylethanolamine is also synthesized from phosphatidylserine at the mitochondrial inner membrane by phosphatidylserine decarboxylase. Phosphatidylserine, itself, is synthesized using a base-exchange reaction with phosphatidylcholine. This reaction is catalyzed by phosphatidylserine synthase which is located in the endoplasmic reticulum membrane.

Phosphatidylethanolamines (PE) are a class of phospholipids that incorporate a phosphoric acid headgroup into a diacylglycerol backbone. They are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In Arabidopsis thaliana, there exist two phosphatidylethanolamine biosynthesis pathways. The first pathway consists of mainly enzymes localized to either the cytosol or the cell membrane. Cell membrane-localized enzymes in this pathway are not drawn as such for clarity. Instead, they are indicated with a dark green colour and appear to be free floating in the cytosol. This first pathway begins with serine decarboxylase catalyzing the biosynthesis of ethanolamine from serine. It requires pyridoxal 5'-phosphate as a cofactor. Next, choline/ethanolamine kinase, localized to the cell membrane, catalyzes the conversion of ethanolamine to phosphoethanolamine. Then ethanolamine-phosphate cytidylyltransferase, localized to the mitochondria outer membrane, catalyzes the conversion of phosphoethanolamine to CDP-ethanolamine. Last, choline/ethanolaminephosphotransferase, localized to the cell membrane, catalyzes phosphatidylethanolamine CDP-ethanolamine, respectively. The second pathway consists of mainly enzymes localized to the endoplasmic reticulum membrane (also depicted in dark green in the image. Beginning in the cytosol, glycerol-3-phosphate dehydrogenase [NAD(+)] catalyzes the interconversion of glycerone phosphate (from glycolysis) and glycerol 3-phosphate. After glycerol 3-phosphate enters the endoplasmic reticulum, glycerol-3-phosphate acyltransferase esterifies the acyl-group from acyl-CoA to the sn-1 position of glycerol-3-phosphate. Third, 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 catalyzes the conversion of lysophosphatidic acid (LPA or 1-acyl-sn-glycerol 3-phosphate) into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by incorporating an acyl moiety at the 2nd position. Fourth, phosphatidate cytidylyltransferase catalyzes the conversion of a 1,2-diacyl-sn-glycerol 3-phosphate into a CDP-diacylglycerol. It requires a magnesium ion as a cofactor. Fifth, CDP-diacylglycerol--serine O-phosphatidyltransferase catalyzes the synthesis of phosphatidylserine from L-serine and a CDP-diacylglycerol. Last, phosphatidylserine decarboxylase catalyzes the formation of phosphatidylethanolamine from phosphatidylserine. It requires pyruvate as a cofactor.

Pefloxacin is an antibiotic used to treat a variety of bacterial infections. Pefloxacin inhibits DNA gyrase (topoisomerase II) and topoisomerase IV. These proteins prevent supercoiling in bacterial DNA. The inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV causes supercoiling of the bacterial DNA. This prevents DNA replication.

Pegaptanib serves as a selective vascular endothelial growth factor (VEGF) antagonist, employed to address neovascular (wet) age-related macular degeneration. This polynucleotide aptamer is designed to bind to VEGF, reducing both angiogenesis and vessel permeability, particularly for neovascular age-related macular degeneration cases. By targeting VEGF, which activates its receptors on vascular endothelial cells, pegaptanib mitigates processes like angiogenesis, increased vascular permeability, and inflammation that contribute to the progression of wet age-related macular degeneration, a significant cause of vision impairment. Pegaptanib's selectivity for VEGF165, a key isoform of VEGF-A responsible for pathological effects in wet AMD, inhibits its binding to receptors, thereby impeding the advancement of the condition without affecting the physiological isoform VEGF121. This treatment approach is especially effective for patients with conditions like wet AMD, where VEGF-A levels are elevated and contribute to disease progression.

Peginterferon alfa-2a is a modified form of recombinant human interferon, which is used to activate interferon alpha receptors in the JAK-STAT pathway. This is used to stimulate the innate antiviral response in the treatment of hepatitis B and C viruses. Peginterferon alfa-2a activate interferon alpha receptors 1 and 2 (IFNAR1 and IFNAR2) which are associated with tyrosine kinase 2 (TYK2) and JAK1 respectively. This receptor complex also phosphorylates STAT3 homodimers. The IFNAR complex phorphoylates STAT5 which binds with Crk-like protein (CRKL). This activates the transcription of gamma activated sequence (GAS) elements, which activates an inflammatory response and immunoregulation. The main pathway of IFNAR1 and IFNAR2 is through the phosphorylation of STAT1 and STAT2. Together with interferon regulatory factor (IRF9) they form the interferon-stimulated gene factor 3 (ISGF3). The ISGF3 translocates to the nucleus and initiates the trascription of Interferon-sensitive response element (ISRE). This leads to an antiviral response, immunoregulation, antigen presentation, and checkpoint proteins. THE ISRE genes also activate IFN regulated genes. These along with lipopolysaccharides or foreign pathogens activates interferon Regulatory Factor 7 (IRF7). IRF7 is phosphorylated and bound with nuclear factor kappa B (NFKB). This causes the induction of type 1 INFs, which further activates the pathway. IFNAR1 and IFNAR2 signal through TYK2 and JAK1 to also trigger the activation of the NFKB pathway through phosphorylated STAT3, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and TNF receptor-associated factors (TRAFs). They act through IKKa and IKKb to drive NFKB induction of genes associated with survival signals, antigen processing and presentation, and proliferation.

Peginterferon alfa-2b, also known as Pegintron or Sylatron, is a purified recombinant human interferon. It is used as part of combination therapy to treat chronic Hepatitis C caused by the Hepatitis C Virus (HCV). It is also used as an adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection. The mechanism of action is the inhibition of the viral replication in infected cells caused by the binding of the peginterferon to the human type 1 interferon receptors causing them to dimerize. This, in consequence, activates the JAK-STATS pathway which increases the expression of multiple genes involved in the innate antiviral response. Its immunomodulatory effects are the enhancement of the phagocytic activity, the activation of NK cells, the stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset.