The lifetime of such an "intermediate" is considerably longer than the lifetime of the intermediates of the esterification reaction itself the tetrahedral intermediate.
In the chemical industry , the term intermediate may also refer to the stable product of a reaction that is itself valuable only as a precursor chemical for other industries. A common example is cumene which is made from benzene and propylene and used to make acetone and phenol in the cumene process. The cumene itself is of relatively little value in and of itself, and is typically only bought and sold by chemical companies.
Cytochrome P 2E1, which plays a role in the breakdown of alcohol and other toxic substances. Ketosteroid reductase, a key enzyme involved in proper digestion i. Researchers have not yet determined the basis for this preferential binding of aldehydes to certain proteins.
It seems, however, that some lysine residues in proteins are particularly reactive with aldehydes and preferentially form adducts because of their local environments i. Other Types of Adducts. Aldehyde—protein adducts are not the only class of adducts formed during alcohol metabolism; another class of adducts involves oxygen radicals generated during alcohol breakdown. For example, cytochrome P 2E1—mediated oxidation of alcohol can result not only in the formation of acetaldehyde but also in the formation of the HER oxygen radical that can readily bind to proteins and form HER—protein adducts.
Because it is highly reactive, HER is likely to react with a variety of different sites on proteins Moncada and Israel ; Worrall and Thiele , generating a range of adducts. Adducts created with proteins are the most widely studied and probably the most important adducts resulting from alcohol metabolism.
Nevertheless, the aldehydes and oxygen radicals generated during alcohol metabolism also can form adducts with other complex molecules, such as DNA or lipids.
Further study of the roles and consequences of these adducts is needed. The fact that it is possible to create adducts through chemical reactions in test tubes i.
Therefore, it is important to verify that adducts are generated in the liver during alcohol consumption. Numerous studies over the years have indicated that chronic alcohol consumption in both animals and humans results in the formation of various protein adducts in the liver; the findings of these studies are summarized in this section.
The first evidence indicating that adducts are generated in vivo as a result of alcohol intake came from studies demonstrating that after proteins have been modified by reactive molecules such as aldehydes, the adducts that are produced can elicit an immune response Niemela The interaction between a foreign molecule and the antibodies produced by the body marks the foreign molecule for destruction by other immune cells.
In most cases, however, the antibodies recognize the modified protein adducts but not the original proteins; therefore, the original proteins can remain in the body and exert their influence without being destroyed by the immune system.
Researchers subsequently have detected antibodies against acetaldehyde, MDA, HNE, MAA, and HER adducts in the blood of animals and humans who chronically consumed alcohol, implying that adducts are formed in the body and then stimulate the production of antibodies Clot et al.
These findings provide indirect evidence that alcohol metabolism in vivo does indeed result in the formation of aldehyde— protein and HER—protein adducts. Direct evidence that adducts form in the livers of animals and humans consuming alcohol was derived from studies using antibodies against specific adducts. For example, several studies Niemela ; Worrall and Thiele have reported the presence of acetaldehyde—protein adducts in the livers of alcohol—fed animals and humans.
These adducts were detected mainly in the principal liver cells i. Various other types of adducts also have been observed, sometimes at specific locations in the liver or liver cells, as follows: Most of the proteins that are modified by acetaldehyde appear to be located in the fluid filling the cells i. Acetaldehyde adducts are found predominantly in a certain region of the liver lobules 2 i. MDA and HNE adducts have been observed in the livers of alcohol—consuming animals; like acetaldehyde adducts, MDA adducts are found at sites in the liver where tissue damage can be detected.
MAA adducts are generated in vivo and appear to involve primarily proteins in the cytosol of liver cells Tuma et al. HER adducts have been detected in the cell membrane and in certain membrane—enclosed cell components i.
Although the formation of adducts in the liver during alcohol consumption has been well established, more information is needed concerning the effects of these adducts on liver cell function and the role they play in liver injury. Recent research in this area has provided some interesting and exciting information on the link between adduct formation and liver dysfunction and injury. These findings may represent a first step in the development of therapeutic interventions that can interfere with adduct formation and its consequences and thereby help reduce the risk of ALD.
One line of evidence concerns the locations of adduct formation and alcohol—related tissue damage in the liver. As mentioned in the previous section, acetaldehyde adducts form primarily in the perivenous region of the liver, which is also the region where alcoholic liver injury starts and predominates, thus supporting the hypothesis that acetaldehyde adducts may contribute to alcoholic liver disease.
Moreover, acetaldehyde adducts are evident in the early phase of ALD, and in advanced liver disease they are found in the same areas that show evidence of inflammation and scar tissue formation i. MDA adducts are found at the same sites as i. Additional studies using a specially bred type of small pig i. Moreover, acetaldehyde and MDA adducts, which increased after alcohol feeding, colocalized with the sites of collagen deposits, a characteristic step in scar tissue formation that occurs prior to fibrosis.
Thus, these findings indicate a link between acetaldehyde and MDA adducts and the subsequent development of fibrosis in the perivenous region. Researchers have identified several mechanisms through which various adducts could contribute to liver damage.
As mentioned earlier, aldehydes interact primarily with the amino acid lysine. Examples of such proteins include the lysine—dependent enzymes, the regulatory protein calmodulin, and the cytoskeletal protein tubulin. Acetaldehyde—tubulin adducts appear to be especially important and relevant to alcohol—induced liver injury.
Studies have shown that modification of only 5 percent of the individual molecules of a certain type of tubulin i. Impaired microtubule function likely accounts for the observed defects in protein secretion and other protein transport pathways in the liver that result from chronic alcohol consumption Tuma and Sorrell ; Tuma et al.
This altered microtubule function also could lead to a considerable disorganization of the hepatocytes that is characterized by various structural changes and which could progress to more severe liver damage in alcohol abusers. Investigators have described impaired function of numerous proteins other than tubulin by adduct formation; however, the role of these adducts in liver dysfunction and injury remains to be established. Another important process in the liver that is affected when adduct formation interferes with the functions of proteins is extracellular matrix production.
The extracellular matrix is a set of proteins e. Disturbances in extracellular matrix production could lead to the formation of scar tissue in the liver i. Many studies have shown that acetaldehyde as well as HNE and MDA increase collagen production in various types of liver cells, such as fibroblasts and activated stellate cells 3 Niemela ; Tuma and Sorrell The intriguing possibility that adduct—stimulated collagen production may contribute to the overall process of alcoholic hepatic fibrosis has not been completely evaluated.
Another interesting mechanism by which adducts could induce liver injury involves the immune system Klassen et al. Numerous studies have shown that aldehyde—protein and HER—protein adducts elicit a distinct immune response, and additional analyses have demonstrated that antibodies against such adducts are present in both humans and animals following chronic alcohol exposure. These findings have led to the hypothesis that adducts formed as a result of alcohol consumption may be recognized by the immune system and may trigger harmful immune responses that could lead to liver damage.
This hypothesis is supported by findings that hepatitis can be induced in guinea pigs by feeding alcohol to animals previously immunized with acetaldehyde adducts Yokoyama et al. Further studies are necessary to evaluate the exact roles of adducts and the immune system in the development of alcohol—induced liver injury. Recently, researchers also have devoted considerable attention to the role of the two main MAA adducts in liver injury. Acetaldehyde and MDA can interact with each other and then modify other proteins to form MAA adducts, and conditions in the liver during chronic alcohol metabolism should actually favor the formation of those hybrid MAA adducts over the formation of the individual acetaldehyde and MDA adducts.
Therefore, MAA adducts may well represent the most prevalent aldehyde adducts formed in the liver after alcohol consumption. Effects Involving the Immune System. MAA adducts elicit a potent immune response that may represent an important event in the development of alcoholic liver injury.
Several lines of evidence are consistent with this hypothesis Thiele et al. Unlike most antibody responses, however, these antibodies sometimes also recognize certain regions of the original proteins, even protein regions that normally identify the protein as belonging to the body and which therefore should not cause an immune response.
An immune response to proteins that belong to the body resulting in the destruction of those normal proteins, however, can be highly detrimental to the organism. Antibodies against MAA adducts circulating throughout the body have been observed in alcohol—fed animals and in humans with alcoholic liver disease; moreover, the levels of these antibodies correlated with the severity of liver injury.
MAA modification of a certain protein found in the liver elicited a specific type of immune response. Taken together, these findings suggest that the formation of MAA—protein adducts generates harmful compounds that could trigger destructive immune responses targeting liver cells; however, further studies are needed to elucidate this proposed mechanism.
Other investigators have demonstrated that MAA adducts can directly induce processes that promote inflammation and fibrosis in two types of liver cells—the previously mentioned stellate cells and the endothelial cells that line the walls of the small channels that allow blood to flow through the liver Thiele et al.
Exposure of these two cell types to MAA adducts in vitro caused:
Intermediate products under tariff heading Mixtures of fermented beverages with the addition of distilled alcohol Mixtures of fermented beverages and non-fermented beverages, not elsewhere specified or included, with the addition of distilled alcohol.
• Intermediate products – All alcoholic beverages between % vol and 22% vol, which cannot be regarded as beer or wine. Generally fermented beverages to which ethyl alcohol has been added. Microsoft PowerPoint - Excise duty Alcohol - ivujoz.tk Author: kozum.
Intermediate products. Intermediate products include port, sherry and vermouth. Alcohol has been added to intermediate products after the natural fermentation process. Different excise duty tariffs apply to sparkling intermediate products and non-sparkling intermediate products. Vegetable and animal oils (energy products) Products falling within CN codes to , if these are intended for use as heating fuel or motor fuel E Mineral oils (energy products) Products failing within CN codes 10, 20, 30, and
The intermediate stage furfuryl alcohol condensation products may be modified. with the described furfuryl alcohol intermediate stage ivujoz.tkdehyde: a toxic byproduct—Much of the research on alcohol metabolism has focused on an intermediate byproduct that occurs early in the breakdown process. Potentially toxic products resulting from the breakdown, or metabolism, of alcohol (chemically known as ethanol). The major alcohol–metabolizing enzymes are alcohol dehydrogenase and .