Benzoyl-CoA then combines the two units to form cocaine. N-methyl-pyrrolinium cation
The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete. Ornithine then undergoes a pyridoxal phosphate-dependent decarboxylation to form putrescine. In some animals, the urea cycle derives putrescine from ornithine. L-ornithine is converted to L-arginine, which is then decarboxylated via PLP to form agmatine. Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N-methyl-Δ1-pyrrolinium cation. Robert Robinsons acetonedicarboxylate
The biosynthesis of the tropane alkaloid is still not understood. Hemscheidt proposes that Robinsons acetonedicarboxylate emerges as a potential intermediate for this reaction. Condensation of N-methylpyrrolinium and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation. Reduction of tropinone
The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized in multiple plant species. These plant species all contain two types of the reductase enzymes, tropinone reductase I and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine.
Cocaine (from French: cocaïne, from Spanish: coca, ultimately from Quechua: kúka) is a stimulant drug obtained from the leaves of two Coca species native to South America, Erythroxylum coca and Erythroxylum novogranatense. After extraction from coca leaves and further processing into cocaine hydrochloride (powdered cocaine), the drug may be snorted, heated until sublimated and then inhaled, or dissolved and injected into a vein. Cocaine stimulates the reward pathway in the brain. Mental effects may include an intense feeling of happiness, sexual arousal, loss of contact with reality, or agitation. Physical effects may include a fast heart rate, sweating, and dilated pupils. High doses can result in high blood pressure or high body temperature. Effects begin within seconds to minutes of use and last between five and ninety minutes. As cocaine also has numbing and blood vessel constriction properties, it is occasionally used during surgery on the throat or inside of the nose to control pain, bleeding, and vocal cord spasm.Cocaine crosses the blood-brain barrier via a proton-coupled organic cation antiporter and (to a lesser extent) via passive diffusion across cell membranes. Cocaine blocks the dopamine transporter, inhibiting reuptake of dopamine from the synaptic cleft into the pre-synaptic axon terminal; the higher dopamine levels in the synaptic cleft increase dopamine receptor activation in the post-synaptic neuron, causing euphoria and arousal.