Pathways

The metY-rimP-nusA-infB-rfbA-truB-rpsO-pnp operon in E. coli contains eight genes involved in the 30S ribosome subunit formation, as well as transcription, translation and tRNA formation. The operon can be activated by DNA-binding protein Fis, which binds to the promoter region and activates transcription of the operon. The operon can also be inactivated by either cAMP-activated global transcriptional regulator CRP or an arginine repressor. When cAMP binds to CRP, it activates it, allowing it to bind to the promoter region, preventing transcription of the operon. Similarly, L-arginine can form a complex with six subunits of the ArgR protein, forming an arginine repressor that binds to and inhibits the transcription of the operon. This operon also has multiple terminators, and if they are formed under certain conditions, can prevent the rest of the operon from being transcribed. The first gene in the operon, metY, encodes a tRNA molecule with the anticodon CAU, which corresponds to the amino acid methionine. The second gene, rimP, encodes the ribosome maturation factor RimP, which is involved in the maturation of the 30S ribosomal subunit. The third gene, nusA, encodes the transcription termination/antitermination protein NusA, which is involved in the termination and antitermination of transcription, as well as having a role in response to DNA damage. The fourth gene, infB, encodes the translation initiation factor IF-2, which is a protein essential for the initiation of protein synthesis, as it ensures the proper binding of N-Formomethionine (fMet), a methionine molecule with a formyl group added to its amino group which is necessary for the initiation of protein synthesis in bacteria. The fifth gene, rbfA, encodes a 30S ribosome-binding factor which is involved in the maturation of the ribosomal 30S subunit. The sixth gene, truB, encodes tRNA pseudouridine synthase B, which synthesizes pseudouridine, which is present in tRNA of E. coli, and allows it to be more thermally stable. The seventh gene, rpsO, encodes the 30S ribosomal protein S15, a protein that makes up the ribosomal 30S subunit, and it directly binds to the 16S rRNA, another component of the 30S subunit and a region widely studied in bacteria. The final gene in the operon, pnp, encodes polyribonucleutode nucleotidyltransferase, an enzyme that degrades mRNA, and is also involved in the maturation and degradation of tRNA.

The ptsHI-crr operon in E. coli contains three genes which encode proteins that are part of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PEP group translocation or sugar PTS). This is an active transport system used to bring sugars such as glucose and mannose into the cell. The operon can be activated by the cAMP-activated global transcriptional regulator CRP (CAP), which binds upstream of the promoter region and interacts with RNA polymerase, activating transcription of the operon. The operon can also be inhibited in several locations by various proteins. The catabolite repressor/activator protein Cra can bind to the promoter region, and depending on the binding of CRP, can either activate the operon's transcription if CRP is not bound, or can inhibit it if CRP is bound. Protein mlc is a repressor that can bind to the promoter region of the operon, repressing transcription. It is involved in the repression and regulation of other proteins involved in the sugar PTS. Finally, the N-acetylglucosamine repressor can bind to the promoter region after being activated by the binding of N-acetyl-D-glucosamine 6-phosphate, allowing it to inhibit transcription of the operon. The first gene in the operon, ptsH, encodes the phosphocarrier protein HPr, which is a general carrier protein in the sugar PTS that is not specific to the sugar being transported by the system. It takes a phosphoryl group from phosphoenolpyruvate (PEP) and transfers it to the EIIA domain of the carrier. The second gene, ptsI, encodes phosphoenolpyruvate-protein phosphotransferase, another component of the sugar PTS that is not specific to the sugar. This enzyme is responsible for transferring the phosphoryl group from PEP to the protein HPr. The final gene in the operon, crr, encodes theglucose-specific phosphotransferase enzyme IIA component, which combines with the PTS system N-acetylmuramic acid-specific EIIBC component to form the Enzyme E II protein. First, EIIA takes the phosphoryl group from HPr and transfers it to EIIB. Then EIIB transfers it across the cell membrane to EIIC via glucose, forming glucose-6-phosphate, which does not exit the cell naturally, allowing more glucose to be pumped into the cell forming a gradient.

The ribF-ileS-lspA-fkpB-ispH operon in E. coli contains five genes that encode for various proteins. There are currently no known activators and repressors of this operon. The first gene, ribF, encodes for a bifunctional riboflavin kinase and FMN adenylyltransferase. In the cell, it is used to convert riboflavin to FMN, and then FMN to FAD. The second gene, ileS, encodes the isoleucine tRNA ligase or synthetase, which catalyzes the attachment of the amimno acid isoleucine onto its tRNA, forming a charged tRNA. The third gene, lspA, encodes a lipoprotein signal peptidase. This protein cleaves signal peptides from prolipoproteins, forming the mature lipoprotein, as well as a free signal peptide which is then degraded. The fourth gene, fkpB, encodes a peptidyl-prolyl cis-trans isomerase which works as an isomerase, and also posesses a chaperone activity, assisting in the folding of several ribosomal proteins. The final gene, ispH, encodes 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) reductase. This protein catalyzes the conversion of HMBPP into both dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) as part of the methylerythritol phosphate pathway involved in isoprenoid biosynthesis.

The xylFGHR operon in E. coli contains four genes involved in the transport of xylose into the cell, and the regulation of the operon. This operon is both positively and negatively regulated. It is negatively regulated by the DNA-binding protein Fis, which binds to the promoter region and represses transcription of the operon. The operon can also be activated by the cAMP-activated global transcriptional regulator CRP, which is itself activated by the binding of cAMP. cAMP generally has a higher cellular concentration when glucose is not being used as the primary energy source of the cell, and in such conditions, alternative sources of carbon such as xylose would be needed. When this complex binds to the promoter region, it activates transcription of the operon, leading to increased levels of xylose transport into the cell. The operon can also be activated by the xylose operon regulatory protein, which is activated by the binding of D-xylose. This also binds to and activates transcription of the operon. The first gene in the operon, xylF, encodes a D-xylose-binding periplasmic protein, which exists in the periplasm of the cell and binds to D-xylose. It is a part of the xylose transport system, along with the proteins encoded by xylG and xylH that are responsible for moving xylose against the concentration gradient into the cell. The second gene, xylG, encodes the xylose import ATP-binding protein XylG, which is responsible for providing the energy necessary for the transport of xylose across the membrane and concentration gradient. The third gene, xylH, encodes the xylose transport system permease protein xylH, which is likely responsible for moving xylose molecules across the cell's inner membrane. The final gene in the operon, xylR, encodes the xylose operon regulatory protein, which regulates this operon, as well as tye xylAB operon, which is involved with the breakdown of xylose.

The ydfABC operon in E. coli contains three genes that encode uncharacterized proteins. The genes involved may be prophage genes, and thus have no known function in E. coli. There are no currently known activators or repressors of this operon.

Dihydrocodeine is an opioid analgesic agent used for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Dihydrocodeine is a semi-synthetic opioid analgesic. Dihydrocodeine is metabolized to dihydromorphine, a highly active metabolite with a high affinity for mu opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, dihydromorphine exerts its principal pharmacologic effects on the central nervous system. Dihydromorphine binds on pre-synaptic mu opioid receptors. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as GABA. Less GABA leads to disinhibition of dopamine cell firing in the spinal cord pain transmission neurons. This leads to less pain signaling and analgesia. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. The inhibition of A delta and C pain fibres in the dorsal horn of the spinal cord is very important as it slows the signaling of pain into the spinal cord. Possible opioid related side effects include, but are not limited to, drowsiness, nausea, headache, dry mouth, constipation, difficulty passing urine, and mild euphoria.

Naturally occurring Endogenous compounds in mammals that naturally act like morphine in the opioid pathway include endorphins, enkephalins, and dynorphins. They are often referred to as endogenous opioids. They bind and activate opioid receptors mimicking the effects of opioid drugs like morphine. Endorphins are a group of endogenous opioid peptides that include beta-endorphin, alpha-endorphin, and gamma-endorphin. They are produced primarily in the pituitary gland and the hypothalamus in response to stress and pain. Endorphins bind to mu-opioid receptors and provide pain relief and a sense of well-being. They are sometimes referred to as "natural painkillers. Enkephalins are a class of endogenous opioid peptides that include met-enkephalin and leu-enkephalin. They are distributed widely in the central nervous system and peripheral tissues. Enkephalins bind to both delta-opioid and mu-opioid receptors and play a role in pain modulation, mood regulation, and other physiological functions. Dynorphins are another group of endogenous opioid peptides, with dynorphin A and dynorphin B being the most well-known. They primarily activate kappa-opioid receptors. Dynorphins are distributed throughout the brain and spinal cord and are involved in pain perception, stress responses, and mood regulation.

Naturally occurring Endogenous compounds in mammals that naturally act like morphine in the opioid pathway include endorphins, enkephalins, and dynorphins. They are often referred to as endogenous opioids. They bind and activate opioid receptors mimicking the effects of opioid drugs like morphine. Endorphins are a group of endogenous opioid peptides that include beta-endorphin, alpha-endorphin, and gamma-endorphin. They are produced primarily in the pituitary gland and the hypothalamus in response to stress and pain. Endorphins bind to mu-opioid receptors and provide pain relief and a sense of well-being. They are sometimes referred to as "natural painkillers. Enkephalins are a class of endogenous opioid peptides that include met-enkephalin and leu-enkephalin. They are distributed widely in the central nervous system and peripheral tissues. Enkephalins bind to both delta-opioid and mu-opioid receptors and play a role in pain modulation, mood regulation, and other physiological functions. Dynorphins are another group of endogenous opioid peptides, with dynorphin A and dynorphin B being the most well-known. They primarily activate kappa-opioid receptors. Dynorphins are distributed throughout the brain and spinal cord and are involved in pain perception, stress responses, and mood regulation.