Sandbox Reserved 346: Difference between revisions
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=='''Structure'''== | =='''Structure'''== | ||
<Structure load='1b4x' size='300' frame='true' align='left' caption='Figure 1 | <Structure load='1b4x' size='300' frame='true' align='left' caption='Figure 1: Asymetric unit of Aspartate aminotransferase, with highlighted small and large domain and PLP cofactor' scene='Sandbox_Reserved_346/Ast/1'/> | ||
<scene name='Sandbox_Reserved_346/Ast/1'>AST</scene> is a homodimer that contains 16 α-helices and a β-sheet formed from 7 parallel and antiparallel strands<ref name ="AST Structure"/>. Each subunit contains an equivalent active site<ref name ="AST Structure">PMID:2121725</ref>. The subunits connect at two sites: between their large domains and between the N-terminal residues and the large domain on the other subunit<ref name ="AST Structure"/>. This structure of AST varies minutely among organisms ranging from ''E. coli'' to humans<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. As well, the structure of the active site is highly conserved with a sequence homology of 25%<ref name ="AST Structure"/>. | <scene name='Sandbox_Reserved_346/Ast/1'>AST</scene> is a homodimer that contains 16 α-helices and a β-sheet formed from 7 parallel and antiparallel strands<ref name ="AST Structure"/>. Each subunit contains an equivalent active site<ref name ="AST Structure">PMID:2121725</ref>. The subunits connect at two sites: between their large domains and between the N-terminal residues and the large domain on the other subunit<ref name ="AST Structure"/>. This structure of AST varies minutely among organisms ranging from ''E. coli'' to humans<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. As well, the structure of the active site is highly conserved with a sequence homology of 25%<ref name ="AST Structure"/>. | ||
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=='''Function'''== | =='''Function'''== | ||
[[Image:Ast-reaction final copy.JPG|right|thumb|upright=3|Figure 2 | [[Image:Ast-reaction final copy.JPG|right|thumb|upright=3|Figure 2: Transamination reaction of L-aspartate and α-ketoglutarate catalyzed by aspartate aminotransferase]] | ||
AST catalyzes the reversible transamination of the | AST catalyzes the reversible transamination of the α-amino group from L-aspartate to α-ketoglutarate forming oxaloacetate and glutamate<ref name ="AST ROLES AND STRUCTURE"/>. This reactivity is lower in E.coli than in higher eukaryotes, and has broader substrate specificity<ref name ="AST Structure"/>. However, the reaction takes place in the same way<ref name ="AST Structure"/>. Upon introduction of an amino acid substrate, a new Schiff base will form between it and the PLP cofactor<ref name ="AST Structure"/><ref name ="TRANSAMINATION">PMID:5450225</ref>. This causes the amino acid to lose a hydrogen and form a quinoid intermediate, and reprotanation takes place resulting in a ketimine<ref name ="AST Structure"/><ref name ="TRANSAMINATION"/>. Next, the structure is hydrolyzed forming an α-keto acid and pyridoxamine phosphate<ref name ="TRANSAMINATION"/>. 2-methyl aspartate acts as an inhibitor of AST when it forms a Schiif base with the PLP cofactor, rather than aspartate<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. This results in the process stopping at the step prior to the alpha protein elimination<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. | ||
This reaction is essential to maintaining homeostasis in organisms. The four different molecules that can form as a result of this transanimation (oxaloacetate, | This reaction is essential to maintaining homeostasis in organisms. The four different molecules that can form as a result of this transanimation (oxaloacetate, α-ketoglutarate, aspartate, L-glutamate) our critical to a number of metabolic processes<ref name ="OXALOACETATE">PMID:11124972</ref><ref name ="ALPHA-KETOGLUTARATE">PMID:11124972</ref><ref name ="ASPARTATE">PMID:1557428</ref><ref name ="AST ROLES AND STRUCTURE"/><ref name ="glutamate"/>. Oxaloacetate and α-ketoglutarate play a critical role in the Krebs cycle, varying forms of aspartate are important molecules in the urea cycle and participate in gluconeogenesis, and glutamate is an important molecule in metabolic pathways associated with memory<ref name ="OXALOACETATE">PMID:11124972</ref><ref name ="ALPHA-KETOGLUTARATE">PMID:11124972</ref><ref name ="ASPARTATE">PMID:1557428</ref><ref name ="AST ROLES AND STRUCTURE"/><ref name ="glutamate">PMID:15929064</ref>. | ||
=='''Clinical Applications'''== | =='''Clinical Applications'''== | ||
The levels of AST in the body are indicative of tissue damage and disease<ref name ="TISSUE DAMAGE">PMID:8432855</ref>. Normally AST is found in minimal amounts within the blood, however when the organs mentioned above are damaged, AST is released into the blood<ref name ="TISSUE DAMAGE"/>. The amount released is proportional to the level of damage sustained<ref name ="TISSUE DAMAGE"/>. AST levels have been shown to rise substantially within 6 hours of the initial tissue degradation and can stay elevated for up to 4 days<ref name ="TISSUE DAMAGE"/>. AST levels when compared with the levels of other enzymes can be used by physicians to determine where in the body the damage has taken place<ref name ="Liver damage"/>. Comparisons with ALT have proven particularly useful in identifying liver damage such as cirrhosis and hepatitis<ref name ="Liver damage"/>. Under normal condition, AST levels within men are 6-34 IU/L and for women it is 8-40 IU/L<ref name ="TISSUE DAMAGE"/>. | The levels of AST in the body are indicative of tissue damage and disease<ref name ="TISSUE DAMAGE">PMID:8432855</ref>. Normally AST is found in minimal amounts within the blood, however when the organs mentioned above are damaged, AST is released into the blood<ref name ="TISSUE DAMAGE"/>. The amount released is proportional to the level of damage sustained<ref name ="TISSUE DAMAGE"/>. AST levels have been shown to rise substantially within 6 hours of the initial tissue degradation and can stay elevated for up to 4 days<ref name ="TISSUE DAMAGE"/>. AST levels when compared with the levels of other enzymes can be used by physicians to determine where in the body the damage has taken place<ref name ="Liver damage"/>. Comparisons with ALT have proven particularly useful in identifying liver damage such as cirrhosis and hepatitis<ref name ="Liver damage"/>. Under normal condition, AST levels within men are 6-34 IU/L and for women it is 8-40 IU/L<ref name ="TISSUE DAMAGE"/>. | ||
=='''References'''== | =='''References'''== | ||
<References/> | <References/> | ||