Pathways

The creation of L-proline in E. coli starts with L-glutamic acid being phosphorylated through an ATP driven glutamate 5-kinase resulting in a L-glutamic acid 5-phosphate. This compound is then reduced through an NADPH driven gamma glutamyl phosphate reductase resulting in the release of a phosphate, an NADP and a L-glutamic gamma-semialdehyde. L-glutamic gamma-semialdehyde is dehydrated spontaneously, resulting in a release of water,hydrogen ion and 1-Pyrroline-5-carboxylic acid. The latter compound is reduced by an NADPH driven pyrroline-5-carboxylate reductase which is then reduced to L-proline. L-proline works as a repressor of the pyrroline-5-carboxylate reductase enzyme and glutamate 5-kinase. Three genetic loci, proA, proB and proC control the biosynthesis of L-proline in E. coli.The pathway begins with a reaction that is catalyzed by γ-glutamyl kinase, which is encoded by proB. Next, NADPH-dependent reduction of γ-glutamyl phosphate to glutamate-5-semialdehyde, occurs through catalyzation by glutamate-5-semialdehyde dehydrogenase, encoded by proA. Following this, both enzymes join together in a multimeric bi-functional enzyme complex called γ-glutamyl kinase-GP-reductase multienzyme complex. This formation is thought to protect the highly labile glutamyl phosphate from the antagonistic nucleophilic and aqueous environment found in the cell. Finally, NADPH-dependent pyrroline-5-carboxylate reductase encoded by proC catalyzes the reduction of pyrroline 5-carboxylate into L-proline. Proline is metabolized in E. coli by returning to the form of L-glutamate, which is then degraded to α-ketoglutarate,which serves as an intermediary of the TCA cycle. Interestingly enough, L-glutamate, the obligate intermediate of the proline degradation pathway, is not able to serve as an outright source of carbon and energy for E. coli, because the rate at which glutamate transport supplies exogenous glutamate is not adequate. The process by which proline is turned into L-glutamate starts with L-proline interacting with ubiquinone through a bifunctional protein putA resulting in an ubiquinol, a hydrogen ion and a 1-pyrroline-5-carboxylic acid. The latter compound is then hydrated spontaneously resulting in a L-glutamic gamma-semialdehyde. This compound is then processed by interacting with water through an NAD driven bifunctional protein putA resulting in a hydrogen ion, NADH and L-glutamic acid.

Prolidase deficiency is an autosomal recessive disorder. The enzyme prolidase cleaves iminodipeptides with N-terminal proline or hydroxyproline. Collagen has high levels of iminoacids therefore, these dipeptidases are important for collagen metabolism. A defect in this enzyme causes accumulation of imidodipeptides in urine. Symptoms include skin lesions, anemia, dysmorphism, mental retardation, and ptosis (drooping eyelid).

Prolidase deficiency is an autosomal recessive disorder. The enzyme prolidase cleaves iminodipeptides with N-terminal proline or hydroxyproline. Collagen has high levels of iminoacids therefore, these dipeptidases are important for collagen metabolism. A defect in this enzyme causes accumulation of imidodipeptides in urine. Symptoms include skin lesions, anemia, dysmorphism, mental retardation, and ptosis (drooping eyelid).

Prolidase deficiency is an autosomal recessive disorder. The enzyme prolidase cleaves iminodipeptides with N-terminal proline or hydroxyproline. Collagen has high levels of iminoacids therefore, these dipeptidases are important for collagen metabolism. A defect in this enzyme causes accumulation of imidodipeptides in urine. Symptoms include skin lesions, anemia, dysmorphism, mental retardation, and ptosis (drooping eyelid).

Metabolites of Proguanil are predicted with biotransformer.

Proflavine is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Proflavine passes through the liver and is then excreted from the body mainly through the kidney.

Profenamine, also known as Ethopropazine, is an antidyskinetic phenothiazine used to treat symptoms of Parkinson's disease. The drug improves muscle control and reuces stiffness which permits more normal movements of the body. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Because of its anticholinergic action, it is largely devoid of neurotoxic side effects. Profenamine partially blocks central cholinergic receptors, which helps to balance cholinergic and dopaminergic activity in the basal ganglia. This may decrease salivation and lead to smooth muscle relaxation. Profenamine causes a local anaesthetic effect due to the inhibition of NMDA glutamate receptors on nociceptive neuron pathways, which decreases pain. The inhibition of NMDA receptors causes hyperpolarization of the neuron, which prevents depolarizati0on. The excessive release of glutamate and hyperactivation on the dorsal horn neurons of the spinal cord is thought to be an integral feature of neuropathic pain, therefore the inhibition of this significantly decreases pain. Profenamine also inhibits muscarinic acetylcholine receptors M1 on the same neuron. Muscarinic acetylcholine receptors M1 normally would activate the Gq signalling cascade, which causes calcium to be released from the endoplasmic reticulum. This would then lead to depolarization. The inhibition of the muscarinic acetylcholine receptor M1 therefore causes further hyperpolarization of the neuron and prevents depolarization.