Pathways

Propionic acidemia (Ketotic hyperglycinemia) is caused by mutation in the genes encoding propionyl-CoA carboxylase, PCCA or PCCB. The break down of Propionyl-CoA is catalyzed by Propionyl-CoA carboxylase (PCC). Propionyl-CoA plays an important role in amino acid metabolism. A mutation in this enzyme causes accumulation of ammonia and propionylcarnitine (C3) in the blood; carnitine , glutamine, glycine, and propionic acid in the plasma; 3-hydroxypropionic acid, 3-hydroxyvaleric acid, 5-oxoproline, acylcarnitin, glycine, methylcitric acid, propionylglycine and tiglylcine in the urine. Symptoms include cardio myopathy, growth retardation, hypothermia, ketosis, neutropenia, strokelike episodes, pyloric stenosis and spastic diplegia/quadriplegia.

Propionic acidemia (Ketotic hyperglycinemia) is caused by mutation in the genes encoding propionyl-CoA carboxylase, PCCA or PCCB. The break down of Propionyl-CoA is catalyzed by Propionyl-CoA carboxylase (PCC). Propionyl-CoA plays an important role in amino acid metabolism. A mutation in this enzyme causes accumulation of ammonia and propionylcarnitine (C3) in the blood; carnitine , glutamine, glycine, and propionic acid in the plasma; 3-hydroxypropionic acid, 3-hydroxyvaleric acid, 5-oxoproline, acylcarnitin, glycine, methylcitric acid, propionylglycine and tiglylcine in the urine. Symptoms include cardio myopathy, growth retardation, hypothermia, ketosis, neutropenia, strokelike episodes, pyloric stenosis and spastic diplegia/quadriplegia.

Propionic acidemia (Ketotic hyperglycinemia) is caused by mutation in the genes encoding propionyl-CoA carboxylase, PCCA or PCCB. The break down of Propionyl-CoA is catalyzed by Propionyl-CoA carboxylase (PCC). Propionyl-CoA plays an important role in amino acid metabolism. A mutation in this enzyme causes accumulation of ammonia and propionylcarnitine (C3) in the blood; carnitine , glutamine, glycine, and propionic acid in the plasma; 3-hydroxypropionic acid, 3-hydroxyvaleric acid, 5-oxoproline, acylcarnitin, glycine, methylcitric acid, propionylglycine and tiglylcine in the urine. Symptoms include cardio myopathy, growth retardation, hypothermia, ketosis, neutropenia, strokelike episodes, pyloric stenosis and spastic diplegia/quadriplegia.

Propionic acidemia (Ketotic hyperglycinemia) is caused by mutation in the genes encoding propionyl-CoA carboxylase, PCCA or PCCB. The break down of Propionyl-CoA is catalyzed by Propionyl-CoA carboxylase (PCC). Propionyl-CoA plays an important role in amino acid metabolism. A mutation in this enzyme causes accumulation of ammonia and propionylcarnitine (C3) in the blood; carnitine , glutamine, glycine, and propionic acid in the plasma; 3-hydroxypropionic acid, 3-hydroxyvaleric acid, 5-oxoproline, acylcarnitin, glycine, methylcitric acid, propionylglycine and tiglylcine in the urine. Symptoms include cardio myopathy, growth retardation, hypothermia, ketosis, neutropenia, strokelike episodes, pyloric stenosis and spastic diplegia/quadriplegia.

Propiverine is an antimuscarinic agent used to treat urinary incontinence or increased urinary frequency or urgency. It can be found under the brand name Mictoryl. Propiverine demonstrates both anticholinergic and calcium-modulating properties. The efferent connection of the pelvic nerve is inhibited due to the anticholinergic action exerted by this drug, leading to relaxation of bladder smooth muscle. Propiverine blocks calcium ion influx and modulates the intracellular calcium in urinary bladder smooth muscle cells, resulting in the inhibition of muscle spasm. The bladder contains several muscarinic receptors. Acetylcholine is the main contractile neurotransmitter in the human bladder detrusor muscle, and antimuscarinics such as propiverine exert their effects by competitively inhibiting the binding of acetylcholine at muscarinic receptors on detrusor smooth muscle cells and other structures within the bladder wall. In one study, After oral treatment with propiverine, the bladder showed the highest concentration of M-2, indicating a targeted distribution of this metabolite into the bladder. Therefore, muscarinic receptor-2 may highly contribute to the relatively selective and long-lasting occupation of bladder muscarinic receptors after oral ingestion of propiverine. Possible side effects of using propiverine may include dry mouth, headache, constipation, dizziness.

Propofol is sedative-hypnotic agent injected intravenously to induce and maintain general anaesthesia causing unconsciousness in order to preform surgery. The injection of Propofol produces hypnosis rapidly within 40 seconds from the start of the injection. The rapid rate of induction is caused by the speed in which Propofol can travel through the blood plasma to the CNS. Recovery from Propofol induced anaesthesia is also rapid, with few side-effects. In the CNS Propofol inhibits voltage-gated sodium channels in the axon of neurons. This sodium ions from entering the neuron, and therefore prevents depolarization. The prevention of depolarization means the neuron cannot fire, which means it cannot send an action potential to the presynapse, which then cannot release neurotransmitters to signal the next neuron to fire. Propofol further ensures no action potential can occur by activating GABA A receptors. Propofol attaches to subunit beta-2 and subunit beta-3 of the GABA A receptors. GABA A receptors increase the amount of chloride ions entering the postsynaptic neuron which causes hyperpolarization. Hyperpolarization is when the potential is a negative value, which makes depolarization more difficult to achieve, further preventing neurons from firing action potentials. This inactivity in the brain causes a sedative-hypnotic effect. Propofol also travels to skeletal muscles where it inhibits a voltage-gated sodium channel with protein type 4 subunit alpha. This specific voltage-gated sodium channel is only present in skeletal muscles. Voltage-gated sodium channels in skeletal muscles perpetuate action potentials in the tubule from the depolarization caused by nicotinic Acetylcholine receptors (nAchR). The prevention of action potential in the muscle cell prevents the muscle from contracting.

Propofol is injected intravenously where 95-99% of the drug is bound to serum albumin and hemoglobin. 1-5% of it goes to the brain and skeletal muscles to preform its mechanism of action. The rest travels to the liver where it is transported a liver transporter like OCT1 into the liver. In the endoplasmic reticulum membrane of the liver, Propofol is metabolized by Cytochrome P450 2C9 or Cytochrome P450 2B6 to make the active metabolite 4-Hydroxypropofol. 4-Hydroxypropofol has a third of the hypnotic ability of Propofol. 4-Hydroxypropofol is further metabolized by UDP-glucuronosyltransferase 1-8, UDP-glucuronosyltransferase 1-9 to make the metabolite 1-Quinol glucuronide. 4-Hydroxypropofol can also be metabolized by an unknown enzyme to make the metabolite 4-Quinol sulfate. There is also a possibility that 4-Hydroxypropofol does not metabolize into further metabolites and remains as is. Propofol also metabolizes into the metabolite Propofol glucuronide with the enzyme UDP-glucuronosyltransferase 1-8 or the enzyme UDP-glucuronosyltransferase 1-9. This further is metabolized into the metabolite 1-Quinol glucuronide with an unknown enzyme. All of these metabolites are transported back into the blood via a liver transporter such as MRP3. Here they travel to the kidney where they undergo renal excretion. 4-Hydroypropofol as an active metabolite can have similar effects on the brain as propofol.