Difference between revisions of "Maple Syrup Urine Disease 2012"

From Bioinformatikpedia
(Summary)
(Summary)
Line 2: Line 2:
 
Maple Syrup Urine Disease is an autosomal recessive disorder, which affects the degradation of the branched amino acids Leu, Ile, Val. The name comes from a maple syrup odor of the urine of affected patients.
 
Maple Syrup Urine Disease is an autosomal recessive disorder, which affects the degradation of the branched amino acids Leu, Ile, Val. The name comes from a maple syrup odor of the urine of affected patients.
 
[[File:Autosomal recessive.jpg|frame|30x30px|right|upright|text-bottom]]
 
[[File:Autosomal recessive.jpg|frame|30x30px|right|upright|text-bottom]]
  +
[[File:Autosomal recessive.jpg|30x30px|testcaption]]
   
 
== Phenotype ==
 
== Phenotype ==

Revision as of 11:30, 21 April 2012

Summary

Maple Syrup Urine Disease is an autosomal recessive disorder, which affects the degradation of the branched amino acids Leu, Ile, Val. The name comes from a maple syrup odor of the urine of affected patients.

Autosomal recessive.jpg

testcaption

Phenotype

Biochemical disease mechanism

MSUD affects a protein called branched-chain alpha-keto acid dehydrogenase complex (BCKDHC), which is involved in the degradation of branched amino acids (Val, Leu, Ile). The inability of degrading these amino acids, leads to an enrichment of those in the body. The elevated levels of amino acids in the urine generate the smell, which is reminiscent of maple syrup. BCKDHC consists of four subunits:

subunit name chromosomal gene location MSUD-type
BCKDHA Branched chain keto acid dehydrogenase E1, alpha polypeptide 19q13.1-q13.2 1a
BCKDHB branched chain keto acid dehydrogenase E1, beta polypeptide 6q14.1 1b
DBT Dihydrolipoamide branched chain transacylase E2 1p31 1/2
DLD dihydrolipoamide dehydrogenase 7q31-q32 3

Kegg-pathway-marked.jpg

Mutations

Reference sequence

Reference sequence (uniprot)

Mutated sequence

  • Nonsense/missense mutatet sequence BCKDHA
>sp|P12694|ODBA_HUMAN 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial OS=Homo sapiens GN=BCKDHA PE=1 SV=2
MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAE
FIDKLEFIQPNVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILY
ESQRQGRISFYMTNYGEEGTHVGSAAALDNMNLVFGQYWEAGVLMNQDYPLELFMAQCYG
NISDLGKGRKMPVHYGCKERHFVTISSPLATQTPQVVGAAYAAKRANANRVVICYFGEGA
ASEGDAHASFNFTATLEYPIIFFWWNSGYAISTPTSEQYRGDDIPA|GPRYGIMSIC/HVD
SNAVFAVYNARKEA|RRAVAENQPFLTKTMTYRIGHHSTSDDSSAYHSVDEVNYWDKQDH
PISWLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLCSDMH/CQEMPA
QLRKQQESLARHLQTYGEHNPLDHFDK
  • Nonsense/missense mutatet sequence BCKDHB


>sp|P21953|ODBB_HUMAN 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial OS=Homo sapiens GN=BCKDHB PE=1 SV=2
MAVVAAAAGWLLRLRAAGAEGHWRRLPGAGLARGFLHPAATVEDAAQRRQVAHFTFQPDP
EPREYGQTQKMNLFQSVTSALDNSLAKDPTAVIFGEDVAFGGVFRCTVGL|DKYGKDRGF
NTLLCEQGIGGFGIRIVVTGATAIAEIQFADYIFPAFDKIVN|AAKYH/CYRSWDLFYCGS
LTIPSPWGCDGHGALYHSQSAEAFFAR/YCPGIKVVKPGSPFQARGLLLSCIEDKNPCIFF
EP|ILHRAAAEEAPIEPYNIPLSQAEVI|EGSDVTLVACSTQVHAI|EVASMAKEKLGVS
CEVIDLRTIIPWDVDTICKSVIKTG|LLISHEAPLTGGFALKISSTVQEECFLNLEALIS
RVCGYDTPFPHIF|PFYIPDKWKC|DALRKMINY
  • Nonsense/missense mutatet sequence DBT (leading to type 1)


>sp|P11182|ODB2_HUMAN Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial OS=Homo sapiens GN=DBT PE=1 SV=3
MAAVRMLRTWSRNAGKLICVRYFQTCGNVHVLKPNYVCFFGYPSFKYSHPHHFLKTTAAL
RGQVVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSMCEVQSDKASVTITSRYDGVIKK
LYYNLDDIAYVRKPLVDTETEALKDSEEDVVETPAVSHDEHTHQEIKGRKTLATPAVRRL
AMENNIKLSEVVG|GKDGRILKEDILNYLEKQTGAILPPSPKV|IMPPPPKPKDMTVPIL
VSKPPVFTGKDKTEPIKGFQKATVKTMSAALKIPHCGYCDEIDLTELVKLREELKPIAFA
RGIKLSSMPFFLNAASLGLLQFPILNASVDENCQNITYKASNNIGIAMDTEQGLIVPNVK
NVQICSIFDIATELNRLQKLGSVSQLSTTGLTGGTFTPSNIGSIGGTFAKQVIMPPEVAI
GALGSIKANPRFNQKGEVYKAQIMNMSWSDDRRVIDGATMSPFSNLWKSYLENPAFMLLD
LK
  • Nonsense/missense mutatet sequence DBT (leading to type 2)
>sp|P11182|ODB2_HUMAN Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial OS=Homo sapiens GN=DBT PE=1 SV=3
MAAVRMLRTWSRNAGKLICVRYFQTCGNVHVLKPNYVCFFGYPSFKYSHPHHFLKTTAAL
RGQVVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSMCEVQSDKASVTITSRYDGVIKK
LYYNLDDIAYVRKPLVDTETEALKDSEEDVVETPAVSHDEHTHQEIKGRKTLATPAVRRL
AMENNIKLSEVVG|GKDGRILKEDILNYLEKQTGAILPPSPKV|IMPPPPKPKDMTVPIL
VSKPPVFTGKDKTEPIKGFQKATVKTMSAALKIPHCGYCDEIDLTELVKLREELKPIAFA
RGIKLSSMPFFLNAASLGLLQFPILNASVDENCQNITYKASNNIGIAMDTEQGLIVPNVK
NVQICSIFDIATELNRLQKLGSVSQLSTTGLTGGTFTPSNIGSIGGTFAKQVIMPPEVAI
GALGSIKANPRFNQKGEVYKAQIMNMSWSDDRRVIDGATMSPFSNLWKSYLENPAFMLLD
LK


  • Nonsense/missense mutatet sequence DLD
>sp|P09622|DLDH_HUMAN Dihydrolipoyl dehydrogenase, mitochondrial OS=Homo sapiens GN=DLD PE=1 SV=2
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA
AQLGFKTVCIEENETLGGTCLNVGCIPSKALLNNSHYYHMAHGTDFASRGIEMSEVRLNL
DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL
IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELCSVWQRLGADVT
AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK
AEVITCDVLLVCIGRRPFTKNLGLEELGIEVDPRGRIPVNTRFQTKIPNIYAIGDVVAGP
MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK
FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI
ARVCHAHLTLSEAFGEANLAASFGKSINF