Sandbox Reserved 1546
From Proteopedia
| Line 5: | Line 5: | ||
==Function== | ==Function== | ||
| - | In order to better understand the function of this 5H86 enzyme, we have to understand the basic processes of Fatty Acid Degradation. Fatty Acid Degradation is the procedure that fatty acids go through to be broken down into their metabolites and it takes place in the mitochondrial matrix. Intermediates in the fatty acid breakdown are covalently attached to the sulfhydryl group of coenzyme A. | + | In order to better understand the function of this 5H86 enzyme, we have to understand the basic processes of Fatty Acid Degradation. Fatty Acid Degradation is the procedure that fatty acids go through to be broken down into their metabolites and it takes place in the mitochondrial matrix <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways">Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 22.4, Fatty Acids Are Synthesized and Degraded by Different Pathways. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22554/</ref>. Intermediates in the fatty acid breakdown are covalently attached to the sulfhydryl group of coenzyme A <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. |
<p>Fatty Acid Degradation happens in three steps:</p> | <p>Fatty Acid Degradation happens in three steps:</p> | ||
| - | <p> 1. '''Lipolysis and release from adipose tissue''': In the initial steps of degradation, fatty acids are stored in adipocytes. The breakdown of adipocytes is called lipolysis | + | <p> 1. '''Lipolysis and release from adipose tissue''': In the initial steps of degradation, fatty acids are stored in the adipocytes <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. The breakdown of adipocytes is called lipolysis where they are then released into the bloodstream to circulate through the body <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>.</p> |
| - | <p> 2. '''Activation and transport into the mitochondria''': The mitochondria is where fatty acid oxidation occurs which activates fatty acids to be carried to the mitochondria. The enzyme responsible for the catalysis of this step is Fatty-Acyl Coa Synthetase. Malonyl ACP is the activated donor of two carbon units in the elongation step which is operated by the release of CO2.</p> | + | <p> 2. '''Activation and transport into the mitochondria''': The mitochondria is where fatty acid oxidation occurs which activates fatty acids to be carried to the mitochondria <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. The enzyme responsible for the catalysis of this step is Fatty-Acyl Coa Synthetase <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. Malonyl ACP is the activated donor of two carbon units in the elongation step which is operated by the release of CO2 <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>.</p> |
| - | <p>3. '''Β-oxidation''': Once inside the mitochodria, five steps occur: 1) Activation by ATP, 2) Oxidation by FAD, 3) Hydration, 4) Oxidation by NAD+, and 5) Thyolysis. The final product is Acetyl-CoA which is now able to be able to enter the TCA cycle <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways" | + | <p>3. '''Β-oxidation''': Once inside the mitochodria, five steps occur: 1) Activation by ATP, 2) Oxidation by FAD, 3) Hydration, 4) Oxidation by NAD+, and 5) Thyolysis <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. The final product is Acetyl-CoA which is now able to be able to enter the TCA cycle <ref name = "Section 22.4 Fatty Acids Are Synthesized and Degraded by Different Pathways"/>. </p> |
| - | <p>One of the enzymes that have a key role in fatty acid degradation and that is also our enzyme of study is known as acyl-CoA acetyltransferase or thiolase. Thiolases are enzymes that have key roles in biochemical pathways and can either be degrative or biosynthetic. Degrative thiolases such as 3-ketoacyl-CoA thiolase, plays a role in fatty-acid β-oxidation in peroxisomes and mitochondria and ketone body metabolism in mitochondria, whereas biosynthetic thiolases, like acetoacetyl-CoA thiolase, catalyzes Acetoacetyl-CoA to two Acetyl-CoAs.</p> | + | <p>One of the enzymes that have a key role in fatty acid degradation and that is also our enzyme of study is known as acyl-CoA acetyltransferase or thiolase. Thiolases are enzymes that have key roles in biochemical pathways and can either be degrative or biosynthetic <ref name = "Biochemistry, 5th edition">Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21154/</ref>. Degrative thiolases such as 3-ketoacyl-CoA thiolase, plays a role in fatty-acid β-oxidation in peroxisomes and mitochondria and ketone body metabolism in mitochondria, whereas biosynthetic thiolases, like acetoacetyl-CoA thiolase, catalyzes Acetoacetyl-CoA to two Acetyl-CoAs <ref name = "Biochemistry, 5th edition"/>.</p> |
<p>[[Image:Thiolase_reaction.PNG|400px|center]]</p> | <p>[[Image:Thiolase_reaction.PNG|400px|center]]</p> | ||
<p><center>'''Figure 1''': Reaction mechanism of Acetoacetyl-CoA to two Acetyl-CoAs with the enzyme thiolase. Image obtained from class powerpoints.</center></p> | <p><center>'''Figure 1''': Reaction mechanism of Acetoacetyl-CoA to two Acetyl-CoAs with the enzyme thiolase. Image obtained from class powerpoints.</center></p> | ||
Revision as of 20:34, 5 May 2019
| This Sandbox is Reserved from May 28 through July 01, 2019 for use in the course Advanced Biochemistry BCHM 4100 taught by Tom Gluick at the Georgia Gwinnett College. This reservation includes Sandbox Reserved 1544 through Sandbox Reserved 1555. |
To get started:
More help: Help:Editing |
Contents |
5H86: HUMAN GCN-5 BOUND TO BUTYRYL-COA
This project was completed by Marianne Javier, Karima MuhummadPoe, and Makayla Yang for Dr. Gluick's Spring 2019 BIOL4100K-01 class at Georgia Gwinnett College.
Project Purpose: We chose this molecule due to its role as a histone acetyltransferase and its role in transcription regulation [1]. It has a harder time having successful enzymatic activity if the acyl-chain is too long which is the purpose of studying the molecule [1]. These researchers made two different acyl-CoA molecules, propionyl-CoA and butyryl-CoA [1]. We are looking at the butyryl-CoA which has a conformation that obstructs the lysine from binding. We chose this molecule to see how Gcn5L2 chooses which acyl-chain donor to have the highest enzymatic activity.
Function
In order to better understand the function of this 5H86 enzyme, we have to understand the basic processes of Fatty Acid Degradation. Fatty Acid Degradation is the procedure that fatty acids go through to be broken down into their metabolites and it takes place in the mitochondrial matrix [2]. Intermediates in the fatty acid breakdown are covalently attached to the sulfhydryl group of coenzyme A [2].
Fatty Acid Degradation happens in three steps:
1. Lipolysis and release from adipose tissue: In the initial steps of degradation, fatty acids are stored in the adipocytes [2]. The breakdown of adipocytes is called lipolysis where they are then released into the bloodstream to circulate through the body [2].
2. Activation and transport into the mitochondria: The mitochondria is where fatty acid oxidation occurs which activates fatty acids to be carried to the mitochondria [2]. The enzyme responsible for the catalysis of this step is Fatty-Acyl Coa Synthetase [2]. Malonyl ACP is the activated donor of two carbon units in the elongation step which is operated by the release of CO2 [2].
3. Β-oxidation: Once inside the mitochodria, five steps occur: 1) Activation by ATP, 2) Oxidation by FAD, 3) Hydration, 4) Oxidation by NAD+, and 5) Thyolysis [2]. The final product is Acetyl-CoA which is now able to be able to enter the TCA cycle [2].
One of the enzymes that have a key role in fatty acid degradation and that is also our enzyme of study is known as acyl-CoA acetyltransferase or thiolase. Thiolases are enzymes that have key roles in biochemical pathways and can either be degrative or biosynthetic [3]. Degrative thiolases such as 3-ketoacyl-CoA thiolase, plays a role in fatty-acid β-oxidation in peroxisomes and mitochondria and ketone body metabolism in mitochondria, whereas biosynthetic thiolases, like acetoacetyl-CoA thiolase, catalyzes Acetoacetyl-CoA to two Acetyl-CoAs [3].
Structural Highlights
| |||||||||||
Relevance
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Donec non nibh hendrerit nunc blandit bibendum. Proin ultrices ex lorem, ac volutpat lorem vestibulum non. Mauris lobortis maximus nulla, a sagittis dui fringilla in. Etiam rhoncus magna a quam placerat, nec viverra urna convallis. Nulla semper ligula sodales tortor elementum molestie. Nullam tincidunt consectetur dui, nec dictum quam tempor quis. Duis ac eros a dui vestibulum feugiat eget sit amet dui.
References
- ↑ 1.0 1.1 1.2 Ringel AE, Wolberger C. Structural basis for acyl-group discrimination by human Gcn5L2. Acta Crystallogr D Struct Biol. 2016 Jul 1;72(Pt 7):841-8. doi:, 10.1107/S2059798316007907. Epub 2016 Jun 23. PMID:27377381 doi:http://dx.doi.org/10.1107/S2059798316007907
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 22.4, Fatty Acids Are Synthesized and Degraded by Different Pathways. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22554/
- ↑ 3.0 3.1 Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21154/
