Proteopedia - User contributions [en]

Sandbox Reserved 1544

2019-05-03T02:37:29Z

Marlyne Serratos:

{{ Sandbox_Reserved_GGC_BHCM4100_1}}
<Structure load='1ege' size='350' side='right' caption='Acyl-CoA Dehydrogenase' scene='49/491924/Cv/1'>

__TOC__
== Function ==

The first reaction in β-oxidation, or fatty acid metabolism, is the catalyzation of the ester bond (C2 and C3) of the substrate Acyl-CoA. This is accomplished through '''Acyl-CoA Dehydrogenase (ACDH)''' and its cofactor FAD. ACDH is classified according to its length of its substrates: short (SCAD), medium (MCAD), very and very long-chain (VLCAD).

== Disease ==

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder that affects fatty acid oxidation and can be characterized by a hypoglycemic crisis during times of increased stressed. Expression of MCADD results in a decrease of ketone production and an increase in medium-chain fatty acid concentration. MCADD is a disorder inherited genetically through an autosomal recessive trait, and it is caused by mutations in the medium-chain acyl- CoA dehydrogenase (ACADM) gene. The ACADM gene is located on chromosome 1p31. There are over 90 different ACADM gene mutations known so far, most of which are missense mutations. The disorder can lead to symptoms such as a loss in appetite as well as vomiting and diarrhea. This can result in accumulated concentrations of acylcarnitine, which can be potentially toxic. People who are affected and not diagnosed are at a high risk of dying or experiencing permanent neurological damage during their first metabolic crisis. To prevent such events, immediate care should follow catabolic stress and fasting should be averted. Individuals living with MCADD are asymptomatic up until there is an increased demand for energy followed by a prolonged time of fasting. Newborn screening is now widely implemented through the use of liquid chromatography-tandem mass spectrometry.

== Relevance ==

== Structural highlights ==

'''Catalytic Residues'''

Glu255 is responsible for the catalytic activity of mutant Medium Chain Acyl-CoA Dehydrogenase (MCADH). It can be in “active” or “resting” states. It is mostly in the “resting” state, due to its ability to hydrogen bond with Glu99.

Long Chain Acyl-CoA Dehydrogenase (LCADH) and Isovaleryl-CoA Dehydrogenase (IVDH) have a higher catalytic activity than MCADH because they have serine and glycine in their 99 position, respectively. Neither of these amino acids can form hydrogen bonds, so the Glu255 is in the “active state.” The catalytic residue of LCADH is Glu261; the catalytic residue of IVDH is Glu254.

Glu376 is the amino acid responsible for catalytic activity of the wild type.

'''Significance of the Positions of Glutamate on the Wild Type (Glu376) and Mutant (Glu255)'''

The distance between the donor proton and the base that attacks the donor proton affect the catalytic activity of the carboxylate base of the glutamates. The distance between the proton and glutamates carboxylates are more than 4.0 A.

Glu376 would conform so that its carboxylate oxygen lies close to the proton (2.4A).

Glu255 has a smaller catalytic activity because is over 4.0 A away from the proton. It is thought that due to MCADH’s flexibility at Gly376, Glu255’s carboxylate oxygen will be closer to the donor proton.

When both Glu255 and Glu376 are available to the Thr255Glu mutant, Glu376 can act as a catalytic residue and Glu255 adopts the “resting” conformation. This is expected given that the kinetic parameters of the mutant and its optimum substrates (C8- and C10-CoA) are similar to those of the wild type enzyme. The substrates (in both wild type and MLCADH) with alkyl chain lengths that are longer than C12-CoA can form multiple conformers at its ω-end in the active site cavity. However, this is not the case for the Glu/Glu mutant due to the glutamate side chains. This steric hindrance prevents the binding of the long substrate in an orientation that would allow catalysis to occur.

'''Solvent Accessibility and Oxygen Reactivity.'''
In the MLCADH, the bore of the active site cavity at its midsection is wider and allows the longer substrate to adopt multiple conformations at its ω-end. This better accommodates the MLCADH for catalysis than the wild type. The wider bore also allows bulkier substrates to bind to the enzyme more easily. Having a larger active site allows more solvent molecules, which leads to larger amounts of molecular oxygen, which is becomes readily available to reduced Flavin. This difference in width (8.5 Å vs 5.1 Å) allows for the oxidation of the reduced Flavin to occur somewhere between 10 to 100 times faster than the wild type. Ligands that lack the carbonyl oxygen are much less effective at protecting the reduced enzyme flavin toward molecular oxygen.

== References ==

<references/>

Sandbox Reserved 1544

2019-04-08T19:20:45Z

Marlyne Serratos:

{{ Sandbox_Reserved_GGC_BHCM4100_1}}
==Structure==
<StructureSection load='1ege' size='340' side='right' caption='Acyl CoA Dehydrogenase' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Each subunit of a medium-chain acyl-CoA dehydrogenase enzyme is composed of three structural domains. The N-terminal 𝛼-helix domain, the 𝛽-sheet domain, and the C-terminal 𝛼-helix domain.

== Function ==

== Disease ==
Short chain acyl-CoA dehydrogenase deficiency (SCADD) is a genetically inherited disorder affecting mitochondrial fatty acid oxidation. SCADD results in an increase concentration of butyrylcarnitine and ethylmalonic acid in the urine and the plasma. Symptoms of SCADD can range from asymptomatic to severe metabolic or neurotransmitter disabilities. This means that individuals affected by SCADD may show no symptoms at all or a very severe phenotype. Most of the mutations that cause SCADD are missense mutations and impair protein folding. This can result in a toxic accumulation of the impaired protein, which can lead to oxidative stress. The genes that cause SCADD and their associations are widely questioned and as a result, SCADD screening is often not on required for newborn babies.
Short chain acyl-CoA dehydrogenase deficiency is an autosomal recessive disorder. This mutation is caused by alterations in the gene ACADS.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder that affects fatty acid oxidation and can be characterized by a hypoglycemic crisis during times of increased stressed. This deficiency is the most common metabolic defect of fatty acid oxidation. MCADD is a flavoprotein that catalyzes the first reaction in 𝛽-oxidation of fatty acids. Such metabolic reactions are necessary for energy production, especially during periods of fasting. Expression of MCADD results in a decrease of ketone production and an increase in medium-chain fatty acid concentration.
MCADD is a disorder inherited genetically through an autosomal recessive trait, and it is caused by mutations in the medium-chain acyl- CoA dehydrogenase (ACADM) gene. The ACADM gene is located on chromosome 1p31. There are over 90 different ACADM gene mutations known so far, most of which are missense mutations.The disorder can lead to symptoms such as a loss in appetite as well as vomiting and diarrhea. This can result in accumulated concentrations of acylcarnitine, which can be potentially toxic. People who are affected and not diagnosed are at a high risk of dying or experiencing permanent neurological damage during their first metabolic crisis. To prevent such events, immediate care should follow catabolic stress and fasting should be averted. Individuals living with MCADD are asymptomatic up until there is an increased demand for energy followed by a prolonged time of fasting. Newborn screening is now widely implemented through the use of liquid chromatography-tandem mass spectrometry.

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1544

2019-04-08T18:31:22Z

Marlyne Serratos:

{{ Sandbox_Reserved_GGC_BHCM4100_1}}
==Structure==
<StructureSection load='1ege' size='340' side='right' caption='Acyl CoA Dehydrogenase' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Each subunit of a medium-chain acyl-CoA dehydrogenase enzyme is composed of three structural domains. The N-terminal 𝛼-helix domain, the 𝛽-sheet domain, and the C-terminal 𝛼-helix domain.

== Function ==

== Disease ==
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder that affects fatty acid oxidation and can be characterized by a hypoglycemic crisis during times of increased stressed. This deficiency is the most common metabolic defect of fatty acid oxidation. MCADD is a flavoprotein that catalyzes the first reaction in 𝛽-oxidation of fatty acids. Such metabolic reactions are necessary for energy production, especially during periods of fasting. Expression of MCADD results in a decrease of ketone production and an increase in medium-chain fatty acid concentration.
MCADD is a disorder inherited genetically through an autosomal recessive trait, and it is caused by mutations in the medium-chain acyl- CoA dehydrogenase (ACADM) gene. The ACADM gene is located on chromosome 1p31. There are over 90 different ACADM gene mutations known so far, most of which are missense mutations.
The disorder can lead to symptoms such as a loss in appetite as well as vomiting and diarrhea. This can result in accumulated concentrations of acylcarnitine, which can be potentially toxic. People who are affected and not diagnosed are at a high risk of dying or experiencing permanent neurological damage during their first metabolic crisis. To prevent such events, immediate care should follow catabolic stress and fasting should be averted. Individuals living with MCADD are asymptomatic up until there is an increased demand for energy followed by a prolonged time of fasting. Newborn screening is now widely implemented through the use of liquid chromatography-tandem mass spectrometry.

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1544

2019-04-08T16:14:24Z

Marlyne Serratos:

{{ Sandbox_Reserved_GGC_BHCM4100_1}}
==Structure==
<StructureSection load='1ege' size='340' side='right' caption='Acyl CoA Dehydrogenase' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Each subunit of a medium-chain acyl-CoA dehydrogenase enzyme is composed of three structural domains. The N-terminal 𝛼-helix domain, the 𝛽-sheet domain, and the C-terminal 𝛼-helix domain.

== Function ==

== Disease ==
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder that affects fatty acid oxidation and can be characterized by a hypoglycemic crisis during times of increased stressed. This deficiency is the most common metabolic defect of fatty acid oxidation. MCADD is a flavoprotein that catalyzes the first reaction in 𝛽-oxidation of fatty acids. Such metabolic reactions are necessary for energy production, especially during periods of fasting. Expression of MCADD results in a decrease of ketone production and an increase in medium-chain fatty acid concentration.
MCADD is a disorder inherited genetically through an autosomal recessive trait, and it is caused by mutations in the medium-chain acyl- CoA dehydrogenase (ACADM) gene. The ACADM gene is located on chromosome 1p31. There are over 90 different ACADM gene mutations known so far, most of which are missense mutations.
The disorder can lead to symptoms such as a loss in appetite as well as vomiting and diarrhea. This can result in accumulated concentrations of acylcarnitine, which can be potentially toxic. People who are affected and not diagnosed are at a high risk of dying or experiencing permanent neurological damage during their first metabolic crisis. To prevent such events, immediate care should follow catabolic stress and fasting should be averted. Individuals living with MCADD are asymptomatic up until there is an increased demand for energy followed by a prolonged time of fasting. Newborn screening is now widely implemented through the use of liquid chromatography-tandem mass spectrometry.
== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1544

2019-02-12T06:01:36Z

Marlyne Serratos:

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2019-02-12T05:05:24Z

Marlyne Serratos:

Sandbox Reserved 1544

2019-02-12T00:50:11Z

Marlyne Serratos:

Sandbox Reserved 1544

2019-02-12T00:48:39Z

Marlyne Serratos: