Pathways

Ethanol metabolism in humans occurs mainly in the liver, though degradation has also been shown in gastric, pancreatic, and lung tissue. Ethanol degradation occurs via four pathways, three of which are oxidative pathways and are depicted here. The fourth is a nonoxidative pathway which is less well studied but known to produce fatty acid ethyl esters. Each of the three oxidative pathways is differentiated by the mechanism utilized to oxidize ethanol to acetaldehyde in the first step. In the alcohol dehydrogenase mediated ethanol degradation pathway (I), cytoplasmic alcohol dehydrogenase produces the acetaldehyde from the ethanol. In the MEOS mediated ethanol degradation pathway (II), the ethanol enters the endoplasmic reticulum, where the Microsomal Ethanol Oxidising System (MEOS), also know as also known as cytochrome P-450 2E1, does the oxidizing and returns the acetaldehyde to the cytoplasm. In the catalase mediated ethanol degradation pathway (III), the oxidation occurs in the peroxisome via peroxisomal catalase, with the resulting acetaldehyde being released to the cytoplasm. In each of the three oxidative pathways the cytosolic acetaldehyde then enters the mitochondrial compartment, where it is converted to acetate by mitochondrial aldehyde dehydrogenase. The acetate leaves the mitochondria and moves to extra-hepatic tissues for further metabolism. In extra-hepatic cells the acetate is converted to acetyl-CoA via either cytoplasmic or mitochondrial acetyl-CoA synthetase. The alcohol dehydrogenase mediated ethanol degradation pathway (I) is the predominant mechanism of catabolism under conditions of acute alcohol consumption. However, under conditions of chronic ethanol consumption the MEOS mediated ethanol degradation pathway (II) and nonoxidative pathway are induced to assist with ethanol degradation.

Pyruvic acid can produce ethanol (the ending product of glycolysis pathway) through two-step reactions, and result in ethanol fermentation. Glycolysis is a metabolic pathway with sequence of ten reactions involving ten intermediate compounds that converts glucose to pyruvate. Glycolysis release free energy for forming high energy compound such as ATP and NADH. Glycolysis is consisted of two phases, which one of them is chemical priming phase and second phase is energy-yielding phase. As the starting compound of chemical priming phase, D-glucose can be obtained from galactose metabolism or imported by monosaccharide-sensing protein 1 from outside of cell. D-Glucose is catalyzed by probable hexokinase-like 2 protein to form glucose 6-phosphate which is powered by ATP. Glucose 6-phosphate transformed to fructose 6-phosphate by glucose-6-phosphate isomerase, which the later compound will be converted to fructose 1,6-bisphosphate, which is the last reaction of chemical priming phase by 6-phosphofructokinase with cofactor magnesium, and it is also powered by ATP. Before entering the second phase, aldolase catalyzing the hydrolysis of F1,6BP into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate and glyceraldehyde 3-phosphate can convert to each other bidirectionally by facilitation of triosephosphate isomerase. The second phase of glycolysis is yielding-energy phase that produce ATP and NADH. At the first step, D-glyceraldehyde 3-phosphate is catalyzed to glyceric acid 1,3-biphosphate by glyceraldehyde-3-phosphate dehydrogenase with NAD, which also generate NADH. ATP is generated through the reaction that convert glyceric acid 1,3-biphosphate to 3-phosphoglyceric acid. Phosphoglycerate mutase 2 catalyze 3-phosphoglyceric acid to 2-Phospho-D-glyceric acid, and alpha-enolase with cofactor magnesium catalyzes 2-Phospho-D-glyceric acid to phosphoenolpyruvic acid. Eventually, plastidial pyruvate kinase 4 converts phosphoenolpyruvic acid to pyruvate with cofactor magnesium and potassium and ADP. Pyruvate will undergo pyruvate metabolism, tyrosine metabolism and pantothenate and CoA biosynthesis.

Ethanol, commonly seen in the form of various alcohols as well as hand sanitizer, is a drug that is injected intrathecally. Ethanol's effects are mainly seen in the brain where it binds to many receptors. The main effects are seen by the binding to GABA receptors, glycine receptors, and glutamate receptors. Ethanol binds to GABA receptors between the alpha and beta subunits, causing them to open more frequently, causing a higher concentration of chloride ions in the post-synaptic neuron. This high concentration of chloride ions causes hyperpolarization of the neuron. Hyperpolarization prevents depolarization and excitability of the neuron which causes a sedative effect in the brain.

Ethanol, commonly seen in the form of various alcohols as well as hand sanitizer, is a drug that is injected intrathecally. Ethanol's effects are mainly seen in the brain where it binds to many receptors. The main effects are seen by the binding to GABA receptors, glycine receptors, and glutamate receptors. Ethanol agonizes glycine receptors, where glycine binds to the alpha subunit. This causes an influx of chlorine ions which hyperpolarizes the neuron. Glycine receptors are present mainly in the spinal cord and brain stem where they control motor function. Therefore, the sedative effect of ethanol activating glycine receptors causes a decrease in motor control. Glycine can also activate GABA receptors if released into the same area, having the same effect on them as GABA.

Ethanol, commonly seen in the form of various alcohols as well as hand sanitizer, is a drug that is injected intrathecally. Ethanol's effects are mainly seen in the brain where it binds to many receptors. The main effects are seen by the binding to GABA receptors, glycine receptors, and glutamate receptors. Glutamate is synthesized from glutamine in either the neuron or glial cells nearby. It is stored as glutamine in the glial cells until it is required. Once released it normally activates glutamate NMDA receptors, however, ethanol binds to NMDA receptors subunit 3A and prevents glutamate from binding to the NDMA receptor on the epsilon-2 subunit. This prevents the calcium channel from opening and allowing calcium into to the post-synaptic neuron. With calcium unable to enter the neuron, the neuron cannot depolarize which stops the signal or makes it much more difficult to get a signal through the neurons. Glutamate NMDA receptors are mainly located in the hippocampus where they are essential in memories and memory storage. In preventing their depolarization, ethanol prevents the creation and storage of memories.

Ethanolamine, in E. coli, is produced through phospholipid biosynthesis. Once in the cytosol it can be used to produce acetaldehyde by reacting with ethanolamine ammonia-lyase resulting in the release of ammonium and acetaldehyde.

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