Browsing Pathways

Tubby protein is a part of a family of proteins called Tubby Like Proteins (TULP) characterized by 260 amino acids that form a helix-filled barrel structure at the carboxylic acid terminal (Tubby domain). Using its Tubby domain to bind phosphatidylinositol 4,5-bisphosphate (PIP2), Tubby proteins are able to localize on the plasma membrane. Through the receptor mediated activation of G-proteins, the enzyme phospholipase C–beta (PLC-beta) hydrolyses PIP2 releasing tubby from the plasma membrane. This triggers protein translocation of tubby to the nucleus allowing tubby to act as a transcription regulator.

The HER4/erbB4-encoded protein, is a transmembrane receptor that contains a cytoplasmic tyrosine kinase domain. This domain exhibits almost 80 percent homologness with the corresponding domain of EGFR (the epidermal growth factor receptor). It was discovered in the 1990s by Plowman et al, that heregulin was responsible for inducing tyrosine phosphorylation of HER4/erbB4. ErbB4 (HER4) receptor is classified as type I GFRs. Where the tyrosine kinase growth factor receptors (GFRs) have been sub-classified into 9 different families based on the structure of their extracellular ligand binding and intracellular kinase domains and the manner in which such protein induce the ligands. Experiments revealed that erbB4 has is readily findable in heart, spleen, breast, muscle, pituitary, kidney, parathyroid, brain, and testis.

Dibucaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Dibucaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore dibucaine preferentially inhibits neurons that are actively firing.

Prilocaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Prilocaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore prilocaine preferentially inhibits neurons that are actively firing.

Alfentanil (also known as Alfenta or Rapifen) is analgesic that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of alfentanil will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Hyperpolarization of neuron is caused by inactivation of calcium channels and activation of potassium channels via facilitated by G-protein.

Carfentanil (also known as Phentanyl or Fentora) is analgesic that can bind to mu-type opioid receptor to activate associated G-protein in the sensory neurons of central nervous system (CNS), which will reduce the level of intracellular cAMP by inhibiting adenylate cyclase. The binding of carfentanil will eventually lead to reduced pain because of decreased nerve conduction and release of neurotransmitter. Hyperpolarization of neuron is caused by inactivation of calcium channels and activation of potassium channels via facilitated by G-protein.

Bupivacaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Bupivacaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore bupivacaine preferentially inhibits neurons that are actively firing.

Acetaminophen (APAP) is metabolized primarily in the liver. Glucuronidation is the main route, accounting for 45-55% of APAP metabolism, and is mediatied by UGT1A1, UGT1A6, UGT1A9, UGT2B15 in the liver and UGT1A10 in the gut. APAP can also by metabolized via sulfation, accounting for 30-35% of the metabolism. In the liver, this step is catalyzed by the sulfotransferases SULT1A1, SULT1A3, SULT1A4, SULT1E1 and SULT2A1. Moreover, APAP can also be activated to form the toxic N-acetyl-p-benzoquinone imine (NAPQI) under the mediation of CYP3A4, CYP2E1, CYP2D6 CYP1A2, CYP2E1 and CYP2A6.

Felbamate is metabolized in the liver. One route of metabolism consists of the hydroxylation to 2-hydroxyfelbamate or p-hydroxyfelbamate, which is catalyzed by CYP2E1 and CYP3A4. Moreover, felbamate can be transformed to 2-phenyl-2-propanediol monocarbamate. This metabolite is then converted to 3-carbamoyl-2phenylpropionaldehyde via alchol dehydrogenase 1A, which in turn can be transformed into three possible metabolites: atropaldehyde, 3-carbamoyl-2-phenylpropionic acid (catalyzed by the dimeric NADP-preferring aldehyde dehydrogenase), and 4-hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one. The latter is further converted by the alcohol dehydrogenase 1A to 5-phenyl-1,3-oxazinane-2,4-dione, which is subsequently transformed to 3-carbamoyl-2-phenylpropionic acid.

A member of the semi-synthetic macrolide class of antibiotics, roxithromycin is employed in infections of the respiratory tract, urinary, and soft tissue infections. Its macrocyclic lactone ring and deoxy sugars, defining features of macrolide antibiotics, mediates its mechanism of action as it inhibits peptide translocation by binding to the 50S subunit of the bacterial ribosome. Protein synthesis is thus inhibited by ribosomal binding. It has been demonstrated to have a longer half-life compared to other macrolide antibiotics such as erythromycin and is effective against certain Gram-negative bacteria.