Share
VIDEOS 1 TO 50
Polygamy Town: Colorado City and it
Polygamy Town: Colorado City and it's recent turn of events
Published: 2014/11/12
Channel: FOX 10 Phoenix
Fumarase deficiency (Medical Condition)
Fumarase deficiency (Medical Condition)
Published: 2015/05/12
Channel: Medical Condition Information
Raising Micah
Raising Micah
Published: 2010/06/05
Channel: carriead3
Fumarase Meaning
Fumarase Meaning
Published: 2015/05/02
Channel: ADictionary
Secrets of Mormon Cult : Breaking Polygamy
Secrets of Mormon Cult : Breaking Polygamy
Published: 2012/11/24
Channel: ShockOfChrist
How to say "fumarase"! (High Quality Voices)
How to say "fumarase"! (High Quality Voices)
Published: 2017/02/09
Channel: WordBox
一夫多妻近親繁殖 極罕怪病禍延後代
一夫多妻近親繁殖 極罕怪病禍延後代
Published: 2017/07/31
Channel: Hong Kong Today
Life After Polygamy: The Daughters & Wives of A Polygamist Cult Reclaim their Hometown
Life After Polygamy: The Daughters & Wives of A Polygamist Cult Reclaim their Hometown
Published: 2016/09/01
Channel: VICE
Former FLDS church members describe Colorado City
Former FLDS church members describe Colorado City
Published: 2016/01/20
Channel: azcentral.com and The Arizona Republic
16x9 - Inside Bountiful: Polygamy investigation
16x9 - Inside Bountiful: Polygamy investigation
Published: 2012/04/11
Channel: 16x9onglobal
What Deadly Diseases Look Like On Your Body
What Deadly Diseases Look Like On Your Body
Published: 2017/02/04
Channel: BuzzFeedBlue
How to Pronounce Fumarase
How to Pronounce Fumarase
Published: 2015/03/07
Channel: Pronunciation Guide
Week3_Reversed micellar and aqueous two phase extraction
Week3_Reversed micellar and aqueous two phase extraction
Published: 2015/09/28
Channel: Principles of Downstream techniques in Bioprocess
Inside the FLDS | Breaking the Faith
Inside the FLDS | Breaking the Faith
Published: 2013/12/23
Channel: TLC
How to pronounce fumarase
How to pronounce fumarase
Published: 2017/02/18
Channel: How to pronounce
Empire Citrate of Mind
Empire Citrate of Mind
Published: 2010/02/01
Channel: iamtomhansen
Colorado City 2016
Colorado City 2016
Published: 2016/07/03
Channel: Elizabeth Mayer
Kidney Cancer Is a Metabolic Disease — W. Marston Linehan, NIH: Part 1
Kidney Cancer Is a Metabolic Disease — W. Marston Linehan, NIH: Part 1
Published: 2014/12/03
Channel: NIH IRP (Intramural Research Program at the National Institutes of Health)
Polygamy Tours Colorado City
Polygamy Tours Colorado City
Published: 2010/10/28
Channel: Business2Businesstv
Glucose
Glucose's Song
Published: 2012/02/23
Channel: Olivia Pochopsky
Medical School - Citric Acid Cycle (Kreb
Medical School - Citric Acid Cycle (Kreb's Cycle) Made Easy
Published: 2013/10/06
Channel: iMedicalSchool
CellX: Overview of The Citric Acid Cycle (HarvardX)
CellX: Overview of The Citric Acid Cycle (HarvardX)
Published: 2017/04/21
Channel: HarvardX
TCA (Kreb
TCA (Kreb's) Cycle Rap - Wilson Lam (Macklemore - Thrift Shop Parody)
Published: 2013/01/20
Channel: 1MaginAZN
MWM 2.10: That Moment You Rip Apart Water to Get Your Oxygen
MWM 2.10: That Moment You Rip Apart Water to Get Your Oxygen
Published: 2017/05/17
Channel: Chris Masterjohn, PhD
Blood study insight could help improve stem cell therapy success.
Blood study insight could help improve stem cell therapy success.
Published: 2017/03/04
Channel: WHATS NEW
Yud the Elk on Mormon Polygamy
Yud the Elk on Mormon Polygamy
Published: 2010/04/20
Channel: owens201001
Giles Johnson (Manchester University) talks to GARNet
Giles Johnson (Manchester University) talks to GARNet
Published: 2016/12/21
Channel: GARNet Community
#29 BB 350 Pentose Phosphate / Citric Acid - Kevin Ahern
#29 BB 350 Pentose Phosphate / Citric Acid - Kevin Ahern's Biochemistry Online
Published: 2012/05/26
Channel: Kevin Ahern
Spice Cells -
Spice Cells - 'Wanna be' (Citric Acid Cycle)
Published: 2012/10/18
Channel: Tayla Doyle
Waltz around the Cycle
Waltz around the Cycle
Published: 2012/11/06
Channel: invisible2sh
Problem Set 7, Problem 1: Tracing Labels through Pathways
Problem Set 7, Problem 1: Tracing Labels through Pathways
Published: 2017/08/22
Channel: MIT OpenCourseWare
28.  Kevin Ahern
28. Kevin Ahern's Biochemistry - Citric Acid Cycle II
Published: 2014/01/09
Channel: Kevin Ahern
30 RARE PHOTOS OF DIVYA BHARTI
30 RARE PHOTOS OF DIVYA BHARTI
Published: 2016/11/06
Channel: Ethnic Channel
Para que vean que hace 1 solo cigarrillo
Para que vean que hace 1 solo cigarrillo
Published: 2009/05/13
Channel: xiraus007
Tea & cake party - fundraiser for Richard House Children
Tea & cake party - fundraiser for Richard House Children's Hospice.
Published: 2015/07/20
Channel: Christina C Beauty
The TCA Cycle Rap -
The TCA Cycle Rap - 'Angel' by Shaggy
Published: 2012/02/01
Channel: Abdullah Aboukarr
Fumarate hydratase, Deuterium depletion, Tumor cell metabolism
Fumarate hydratase, Deuterium depletion, Tumor cell metabolism
Published: 2014/07/01
Channel: Fumarate Hydratase - SiDMAP (Laszlo G. Boros, M.D.)
Steps 5-8 of Citric Acid Cycle
Steps 5-8 of Citric Acid Cycle
Published: 2015/05/27
Channel: AK LECTURES
29. Ahern
29. Ahern's BB 350 at Oregon State University - Citric Acid Cycle
Published: 2017/05/31
Channel: Kevin Ahern
Citric Acid Cycle II
Citric Acid Cycle II
Published: 2010/10/20
Channel: Oregon State University
Citric Acid Cycle II - Kevin Ahern
Citric Acid Cycle II - Kevin Ahern's BB 451 Lecture #30 2017
Published: 2017/01/16
Channel: Kevin Ahern
Cellular Respiration Part 2: The Citric Acid Cycle
Cellular Respiration Part 2: The Citric Acid Cycle
Published: 2016/09/15
Channel: Professor Dave Explains
Gene Music using Protein Sequence of FH "FUMARATE HYDRATASE"
Gene Music using Protein Sequence of FH "FUMARATE HYDRATASE"
Published: 2016/10/24
Channel: Gene Music Studio
Krebs Cycle Song
Krebs Cycle Song
Published: 2011/11/16
Channel: Erio3491
#29 Biochemistry Citric Acid Cycle II Lecture for Kevin Ahern
#29 Biochemistry Citric Acid Cycle II Lecture for Kevin Ahern's BB 451/551
Published: 2012/01/12
Channel: Kevin Ahern
Hệ lụy di truyền thảm khốc ở nơi đàn ông được lấy nhiều vợ
Hệ lụy di truyền thảm khốc ở nơi đàn ông được lấy nhiều vợ
Published: 2017/08/29
Channel: KHOA HỌC
Ahern
Ahern's BB 350 at OSU - 29. Citric Acid Cycle
Published: 2015/05/24
Channel: Kevin Ahern
Hildale, Utah
Hildale, Utah
Published: 2009/09/06
Channel: itayav83
Enzimas - Compostos Orgânicos - Prof. Paulo Jubilut
Enzimas - Compostos Orgânicos - Prof. Paulo Jubilut
Published: 2012/04/01
Channel: Biologia Total com Prof. Jubilut
Galactocele (presented as Breast Lump) : Diagnosis and Treatment
Galactocele (presented as Breast Lump) : Diagnosis and Treatment
Published: 2017/08/03
Channel: Rohan Khandelwal
NEXT
GO TO RESULTS [51 .. 100]

WIKIPEDIA ARTICLE

From Wikipedia, the free encyclopedia
Jump to: navigation, search
FH
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FH, fumarate hydratase, HLRCC, LRCC, MCL, MCUL1, FMRD, Fumarate hydratase
External IDs MGI: 95530 HomoloGene: 115 GeneCards: FH
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for FH
Genomic location for FH
Band 1q43 Start 241,497,603 bp[1]
End 241,519,761 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000143

NM_010209

RefSeq (protein)

NP_000134

NP_034339

Location (UCSC) Chr 1: 241.5 – 241.52 Mb Chr 1: 175.6 – 175.63 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fumarase (or fumarate hydratase) is an enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. Fumarase comes in two forms: mitochondrial and cytosolic. The mitochondrial isoenzyme is involved in the Krebs Cycle (also known as the Tricarboxylic Acid Cycle [TCA] or the Citric Acid Cycle), and the cytosolic isoenzyme is involved in the metabolism of amino acids and fumarate. Subcellular localization is established by the presence of a signal sequence on the amino terminus in the mitochondrial form, while subcellular localization in the cytosolic form is established by the absence of the signal sequence found in the mitochondrial variety.[5]

This enzyme participates in 2 metabolic pathways: citric acid cycle, reductive citric acid cycle (CO2 fixation), and is also important in renal cell carcinoma. Mutations in this gene have been associated with the development of leiomyomas in the skin and uterus in combination with renal cell carcinoma.

Nomenclature[edit]

This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is (S)-malate hydro-lyase (fumarate-forming). Other names in common use include:

  • fumarase
  • L-malate hydro-lyase
  • (S)-malate hydro-lyase

Structure[edit]

Gene[edit]

The FH gene is localized to the chromosomal position 1q42.3-q43. The FH gene contains 10 exons.

Protein[edit]

Crystal structures of fumarase C from Escherichia coli have been observed to have two occupied dicarboxylate binding sites. These are known as the active site and the B site. The active site and B site are both identified as having areas unoccupied by a bound ligand. This so-called ‘free’ crystal structure demonstrates conservation of the active-site water. Similar orientation has been discovered in other fumarase C crystal structures. Crystallographic research on the B site of the enzyme has observed that there is a shift on His129. This information suggests that water is a permanent component of the active site. It also suggests that the use of an imidazole-imidazolium conversion controls access to the allosteric B site.[6]

Function[edit]

Mechanism[edit]

Figure 1: Conversion of fumarate to S-malate.
Figure 2: Conversion of fumarate to S-malate by fumarase through a carbanion intermediate.

Figure 2 depicts the fumarase reaction mechanism. Two acid-base groups catalyze proton transfer, and the ionization state of these groups is in part defined by two forms of the enzyme E1 and E2. In E1, the groups exist in an internally neutralized A-H/B: state, while in E2, they occur in a zwitterionic A-/BH+ state. E1 binds fumarate and facilitates its transformation into malate, and E2 binds malate and facilitates its transformation into fumarate. The two forms must undergo isomerization with each catalytic turnover.[7]

Despite its biological significance, the reaction mechanism of fumarase is not completely understood. The reaction itself can be monitored in either direction; however, it is the formation of fumarate from S-malate in particular that is less understood due to the high pKa value of the HR (Fig. 1) atom that is removed without the aid of any cofactors or coenzymes. However, the reaction from fumarate to L-malate is better understood, and involves a stereospecific hydration of fumarate to produce S-malate by trans-addition of a hydroxyl group and a hydrogen atom through a trans 1,4 addition of a hydroxyl group. Early research into this reaction suggested that the formation of fumarate from S-malate involved dehydration of malate to a carbocationic intermediate, which then loses the alpha proton to form fumarate. This led to the conclusion that in the formation of S-Malate from fumarate E1 elimination, protonation of fumarate to the carbocation was followed by the additional of a hydroxyl group from H2O. However, more recent trials have provided evidence that the mechanism actually takes place through an acid-base catalyzed elimination by means of a carbanionic intermediate E1CB elimination (Figure 2).[7][8][9]

Biochemical pathway[edit]

The function of fumarase in the citric acid cycle is to facilitate a transition step in the production of energy in the form of NADH.[10] In the cytosol the enzyme functions to metabolize fumarate, which is a byproduct of the urea cycle as well as amino acid catabolism. Studies have revealed that the active site is composed of amino acid residues from three of the four subunits within the tetrameric enzyme.[11]

The primary binding site on fumarase is known as catalytic site A. Studies have revealed that catalytic site A is composed of amino acid residues from three of the four subunits within the tetrameric enzyme. Two potential acid-base catalytic residues in the reaction include His 188 and Lys 324.[7][8][9]

Subtypes[edit]

There are two classes of fumarases.[12] Classifications depend on the arrangement of their relative subunit, their metal requirement, and their thermal stability. These include class I and class II. Class I fumarases are able to change state or become inactive when subjected to heat or radiation, are sensitive to superoxide anion, are Iron II (Fe2+) dependent, and are dimeric proteins consisting of around 120 kD. Class II fumarases, found in prokaryotes as well as in eukaryotes, are tetrameric enzymes of 200,000 D that contain three distinct segments of significantly homologous amino acids. They are also iron-independent and thermal-stable. Prokaryotes are known to have three different forms of fumarase: Fumarase A, Fumarase B, and Fumarase C. Fumarase C is a part of the class II fumarases, whereas Fumarase A and Fumarase B from Escherichia coli (E. coli) are classified as class I.[11]

Clinical significance[edit]

Fumarase deficiency is characterized by polyhydramnios and fetal brain abnormalities. In the newborn period, findings include severe neurologic abnormalities, poor feeding, failure to thrive, and hypotonia. Fumarase deficiency is suspected in infants with multiple severe neurologic abnormalities in the absence of an acute metabolic crisis. Inactivity of both cytosolic and mitochondrial forms of fumarase are potential causes. Isolated, increased concentration of fumaric acid on urine organic acid analysis is highly suggestive of fumarase deficiency. Molecular genetic testing for fumarase deficiency is currently available.[12]

Fumarase is prevalent in both fetal and adult tissues. A large percentage of the enzyme is expressed in the skin, parathyroid, lymph, and colon. Mutations in the production and development of fumarase have led to the discovery of several fumarase-related diseases in humans. These include benign mesenchymal tumors of the uterus, leiomyomatosis and renal cell carcinoma, and fumarase deficiency. Germinal mutations in fumarase are associated with two distinct conditions. If the enzyme has missense mutation and in-frame deletions from the 3’ end, fumarase deficiency results. If it contains heterozygous 5’ missense mutation and deletions (ranging from one base pair to the whole gene), then leiomyomatosis and renal cell carcinoma/Reed’s syndrome (multiple cutaneous and uterine leiomyomatosis) could result.[11][12]

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

[[File:
TCACycle_WP78 go to article go to article go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
TCACycle_WP78 go to article go to article go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article
|{{{bSize}}}px|alt=TCA Cycle edit]]
  1. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". 

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000091483 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026526 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ FH (fumarate hydratase)
  6. ^ Weaver T (October 2005). "Structure of free fumarase C from Escherichia coli". Acta Crystallogr. D. 61 (Pt 10): 1395–401. PMID 16204892. doi:10.1107/S0907444905024194. 
  7. ^ a b c Hegemony AD, Frey PA (2007). Enzymatic reaction mechanisms. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-512258-5. 
  8. ^ a b Begley TP, McMurry J (2005). The organic chemistry of biological pathways. Roberts and Co. Publishers. ISBN 0-9747077-1-6. 
  9. ^ a b Walsh C (1979). Enzymatic reaction mechanisms. San Francisco: W. H. Freeman. ISBN 0-7167-0070-0. 
  10. ^ Yogev O, Naamati A, Pines O (2011). "Fumarase: a paradigm of dual targeting and dual localized functions". The FEBS Journal. 278 (22): 4230–42. PMID 21929734. doi:10.1111/j.1742-4658.2011.08359.x. 
  11. ^ a b c Estévez M, Skarda J, Spencer J, Banaszak L, Weaver TM (June 2002). "X-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation". Protein Sci. 11 (6): 1552–7. PMC 2373640Freely accessible. PMID 12021453. doi:10.1110/ps.0201502. [permanent dead link]
  12. ^ a b c Lynch AM, Morton CC (2006-07-01). "FH (fumarate hydratase).". Atlas of Genetics and Cytogenetics in Oncology and Haematology. 

External links[edit]

Disclaimer

None of the audio/visual content is hosted on this site. All media is embedded from other sites such as GoogleVideo, Wikipedia, YouTube etc. Therefore, this site has no control over the copyright issues of the streaming media.

All issues concerning copyright violations should be aimed at the sites hosting the material. This site does not host any of the streaming media and the owner has not uploaded any of the material to the video hosting servers. Anyone can find the same content on Google Video or YouTube by themselves.

The owner of this site cannot know which documentaries are in public domain, which has been uploaded to e.g. YouTube by the owner and which has been uploaded without permission. The copyright owner must contact the source if he wants his material off the Internet completely.

Powered by YouTube
Wikipedia content is licensed under the GFDL and (CC) license