Biosynthesis of cholesterol
From Proteopedia
(Difference between revisions)
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
<StructureSection load='' size='350' side='right' scene='HMG-CoA_Reductase/1dq8_starting_scene/1' caption='Crystal Structure of HMG-CoA, (PDB code [[1dq8]])'> | <StructureSection load='' size='350' side='right' scene='HMG-CoA_Reductase/1dq8_starting_scene/1' caption='Crystal Structure of HMG-CoA, (PDB code [[1dq8]])'> | ||
Synthesis within the body starts with the mevalonate pathway where two molecules of <scene name='43/430893/Cv/2'>acetyl-CoA</scene> condense to form <scene name='92/929923/Cv/1'>acetoacetyl-CoA</scene>. This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form <scene name='92/929923/Cv/2'>3-hydroxy-3-methylglutaryl CoA (HMG-CoA)</scene>. This molecule is then reduced to <scene name='92/929923/Cv/3'>mevalonate</scene> by the enzyme [[HMG-CoA reductase]]. Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins. | Synthesis within the body starts with the mevalonate pathway where two molecules of <scene name='43/430893/Cv/2'>acetyl-CoA</scene> condense to form <scene name='92/929923/Cv/1'>acetoacetyl-CoA</scene>. This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form <scene name='92/929923/Cv/2'>3-hydroxy-3-methylglutaryl CoA (HMG-CoA)</scene>. This molecule is then reduced to <scene name='92/929923/Cv/3'>mevalonate</scene> by the enzyme [[HMG-CoA reductase]]. Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins. | ||
| - | |||
| - | Acetyl-CoA is coming from [[Citric Acid Cycle]]. | ||
'''Mevalonate pathway''' | '''Mevalonate pathway''' | ||
| Line 40: | Line 38: | ||
*[[Sandbox Reserved 333|Mevalonate Diphosphate Decarboxylase]] | *[[Sandbox Reserved 333|Mevalonate Diphosphate Decarboxylase]] | ||
| + | <scene name='92/929923/Cv/7'>mevalonate-5-pyrophosphate</scene> => <scene name='92/929923/Cv/8'>isopentenyl pyrophosphate</scene> | ||
''Isopentenyl pyrophosphate isomerase'' | ''Isopentenyl pyrophosphate isomerase'' | ||
| Line 46: | Line 45: | ||
*[[Isopentenyl-diphosphate delta-isomerase]] | *[[Isopentenyl-diphosphate delta-isomerase]] | ||
| - | + | <scene name='92/929923/Cv/8'>isopentenyl pyrophosphate</scene> => <scene name='92/929923/Cv/9'>dimethylallyl pyrophosphate</scene> | |
| - | + | ||
'''Next steps of Cholesterol Biosynthesis''' | '''Next steps of Cholesterol Biosynthesis''' | ||
| Line 53: | Line 51: | ||
''Geranyl transferase'' | ''Geranyl transferase'' | ||
| - | Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Other names in common use include: | + | Three molecules of <scene name='92/929923/Cv/8'>isopentenyl pyrophosphate</scene> condense to form <scene name='92/929923/Cv/10'>farnesyl pyrophosphate</scene> through the action of geranyl transferase. Other names in common use include: |
*farnesyl-diphosphate synthase | *farnesyl-diphosphate synthase | ||
*geranyl transferase I | *geranyl transferase I | ||
| Line 64: | Line 62: | ||
''Squalene synthase'' | ''Squalene synthase'' | ||
| - | Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. | + | Two molecules of <scene name='92/929923/Cv/10'>farnesyl pyrophosphate</scene> then condense to form <scene name='92/929923/Cv/11'>squalene</scene> by the action of squalene synthase in the endoplasmic reticulum. |
*[[Squalene synthase]] | *[[Squalene synthase]] | ||
Current revision
| |||||||||||
References
- ↑ Sgraja T, Smith TK, Hunter WN. Structure, substrate recognition and reactivity of Leishmania major mevalonate kinase. BMC Struct Biol. 2007 Mar 30;7:20. PMID:17397541 doi:10.1186/1472-6807-7-20
