Sandbox Reserved 346: Difference between revisions

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=='''Structure'''==

<scene name='Sandbox_Reserved_346/Ast/1'>AST</scene> is a homodimer that contains 16 ~~alpha~~ helices and a ~~Beta~~-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"/>.

Each subunit of the homodimer is further divided into a small and large domain<ref name ="AST Structure"/>. The <scene name='Sandbox_Reserved_346/Small_subunit_2/1'>small domain</scene> is comprised of the amino acids from the N-terminus to Pro 48 residue and from Met 326 to the C-terminus<ref name ="AST Structure"/>. The remaining amino acids make up the <scene name='Sandbox_Reserved_346/Large_subunit/1'>large domain</scene>, and the <scene name='Sandbox_Reserved_346/Whole_subunit_2/1'>two domains</scene> are connected by a long ~~alpha helicx~~ consisting of 32 amino acids<ref name ="AST Structure"/>.

Each subunit of the homodimer is further divided into a small and large domain<ref name ="AST Structure"/>. The <scene name='Sandbox_Reserved_346/Small_subunit_2/1'>small domain</scene> is comprised of the amino acids from the N-terminus to Pro 48 residue and from Met 326 to the C-terminus<ref name ="AST Structure"/>. The remaining amino acids make up the <scene name='Sandbox_Reserved_346/Large_subunit/1'>large domain</scene>, and the <scene name='Sandbox_Reserved_346/Whole_subunit_2/1'>two domains</scene> are connected by a long α-helix consisting of 32 amino acids<ref name ="AST Structure"/>.

The large domain is where the active site of AST is found and to accommodate this, the core contains many ~~alpha~~/~~beta~~ supersecondary structures<ref name ="AST Structure"/>. This is contrasted with the core of the small subunit which is formed from two ~~alpha~~ helices and two ~~beta~~ strands<ref name ="AST Structure"/>. In multicellular organisms there is a kink at the 325th residue which acts as a hinge for the small domain, which allows for the resulting conformational changes that take place upon the binding of inhibitors to the enzyme<ref name ="AST Structure"/>.

The large domain is where the active site of AST is found and to accommodate this, the core contains many α/β supersecondary structures<ref name ="AST Structure"/>. This is contrasted with the core of the small subunit which is formed from two α-helices and two β-strands<ref name ="AST Structure"/>. In multicellular organisms there is a kink at the 325th residue which acts as a hinge for the small domain, which allows for the resulting conformational changes that take place upon the binding of inhibitors to the enzyme<ref name ="AST Structure"/>.

As was stated above, the active site of AST is situated on the large domain of the subunit<ref name ="AST Structure"/>. Within the active site is the amino residue Lys 258, also known as the internal aldimine, which binds with the cofactor Pyridoxal 5'-phosphate (<scene name='Sandbox_Reserved_346/Plp/5'>PLP</scene>) forming what is called a [http://en.wikipedia.org/wiki/Schiff_base Schiff base]<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. Upon the addition of an amino acid substrate, a new Schiiff base forms between PLP and the amino acid<ref name ="AST Structure"/>.

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This reaction is essential to maintaining homeostasis in organisms. The four different molecules that can form as a result of this transanimation (oxaloacetate, alpha-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"/>. Oxaloacetate and alpha-ketoglutarate play a critical role in the Krebs cycle and the varying forms of aspartate are important molecules in the urea cycle and participate in gluconeogenesis<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"/>.

=='''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'''==

Sandbox Reserved 346: Difference between revisions

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@@ Line 12: / Line 12: @@
 =='''Structure'''==
 <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 alpha helices and a Beta-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"/>.
-Each subunit of the homodimer is further divided into a small and large domain<ref name ="AST Structure"/>. The <scene name='Sandbox_Reserved_346/Small_subunit_2/1'>small domain</scene> is comprised of the amino acids from the N-terminus to Pro 48 residue and from Met 326  to the C-terminus<ref name ="AST Structure"/>. The remaining amino acids make up the <scene name='Sandbox_Reserved_346/Large_subunit/1'>large domain</scene>, and the <scene name='Sandbox_Reserved_346/Whole_subunit_2/1'>two domains</scene> are connected by a long alpha helicx consisting of 32 amino acids<ref name ="AST Structure"/>.
+Each subunit of the homodimer is further divided into a small and large domain<ref name ="AST Structure"/>. The <scene name='Sandbox_Reserved_346/Small_subunit_2/1'>small domain</scene> is comprised of the amino acids from the N-terminus to Pro 48 residue and from Met 326  to the C-terminus<ref name ="AST Structure"/>. The remaining amino acids make up the <scene name='Sandbox_Reserved_346/Large_subunit/1'>large domain</scene>, and the <scene name='Sandbox_Reserved_346/Whole_subunit_2/1'>two domains</scene> are connected by a long α-helix consisting of 32 amino acids<ref name ="AST Structure"/>.
-The large domain is where the active site of AST is found and to accommodate this, the core contains many alpha/beta supersecondary structures<ref name ="AST Structure"/>. This is contrasted with the core of the small subunit which is formed from two alpha helices and two beta strands<ref name ="AST Structure"/>. In multicellular organisms there is a kink at the 325th residue which acts as a hinge for the small domain, which allows for the resulting conformational changes that take place upon the binding of inhibitors to the enzyme<ref name ="AST Structure"/>.
+The large domain is where the active site of AST is found and to accommodate this, the core contains many α/β supersecondary structures<ref name ="AST Structure"/>. This is contrasted with the core of the small subunit which is formed from two α-helices and two β-strands<ref name ="AST Structure"/>. In multicellular organisms there is a kink at the 325th residue which acts as a hinge for the small domain, which allows for the resulting conformational changes that take place upon the binding of inhibitors to the enzyme<ref name ="AST Structure"/>.
 As was stated above, the active site of AST is situated on the large domain of the subunit<ref name ="AST Structure"/>. Within the active site is the amino residue Lys 258, also known as the internal aldimine, which binds with the cofactor Pyridoxal 5'-phosphate (<scene name='Sandbox_Reserved_346/Plp/5'>PLP</scene>) forming what is called a [http://en.wikipedia.org/wiki/Schiff_base Schiff base]<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. Upon the addition of an amino acid substrate, a new Schiiff base forms between PLP and the amino acid<ref name ="AST Structure"/>.
@@ Line 32: / Line 32: @@
 This reaction is essential to maintaining homeostasis in organisms. The four different molecules that can form as a result of this transanimation (oxaloacetate, alpha-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"/>.  Oxaloacetate and alpha-ketoglutarate play a critical role in the Krebs cycle and the varying forms of aspartate are important molecules in the urea cycle and participate in gluconeogenesis<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"/>.
 =='''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/>