HIBCH mutants don't synthesize beta-hydroxyisobutyrate

Stable Identifier
R-HSA-9916727
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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HIBCH mutants don't synthesize beta-hydroxyisobutyrate
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The following mutations have been identified in patients presenting with Leigh-like disease, are annotated as pathogenic or likely pathogenic by ClinVar, and show decreased protein levels and/or activity in fibroblasts in vitro:

Y122C: Brown et al, 1982; Loutpatty et al, 2007;

C163F: D'Gama et al, 2020;

G317F: Ferdinandusse et al, 2014;

K377*: Reuter et al, 2014;

G345S: Peters et al, 2015.

Literature References
PubMed ID Title Journal Year
7122152 beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations

Brown, GK, Hunt, SM, Scholem, R, Fowler, K, Grimes, A, Mercer, JF, Truscott, RM, Cotton, RG, Rogers, JG, Danks, DM

Pediatrics 1982
25251209 HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders

Reuter, MS, Sass, JO, Leis, T, Köhler, J, Mayr, JA, Feichtinger, RG, Rauh, M, Schanze, I, Bähr, L, Trollmann, R, Uebe, S, Ekici, AB, Reis, A

Am J Med Genet A 2014
24299452 HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase

Ferdinandusse, S, Waterham, HR, Heales, SJ, Brown, GK, Hargreaves, IP, Taanman, JW, Gunny, R, Abulhoul, L, Wanders, RJ, Clayton, PT, Leonard, JV, Rahman, S

Orphanet J Rare Dis 2013
26163321 Metabolite studies in HIBCH and ECHS1 defects: Implications for screening

Peters, H, Ferdinandusse, S, Ruiter, JP, Wanders, RJ, Boneh, A, Pitt, J

Mol Genet Metab 2015
32022391 A phenotypically severe, biochemically "silent" case of HIBCH deficiency in a newborn diagnosed by rapid whole exome sequencing and enzymatic testing

D'Gama, AM, Brucker, WJ, Zhang, T, Gubbels, CS, Ferdinandusse, S, Shi, J, Grant, PE, VanNoy, G, Genetti, CA, Juusola, J, Yu, TW, Kritzer, A, Agrawal, PB

Am J Med Genet A 2020
17160907 Mutations in the gene encoding 3-hydroxyisobutyryl-CoA hydrolase results in progressive infantile neurodegeneration

Loupatty, FJ, Clayton, PT, Ruiter, JP, Ofman, R, Ijlst, L, Brown, GK, Thorburn, DR, Harris, RA, Duran, M, Desousa, C, Krywawych, S, Heales, SJ, Wanders, RJ

Am J Hum Genet 2007
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Catalyst Activity

3-hydroxyisobutyryl-CoA hydrolase activity of HIBCH mutants [mitochondrial matrix]

Physical Entity
HIBCH mutants [mitochondrial matrix] (Homo sapiens)
Activity
3-hydroxyisobutyryl-CoA hydrolase activity (GO:0003860)
Normal reaction
beta-hydroxyisobutyryl-CoA + H2O => beta-hydroxyisobutyrate + CoA (Homo sapiens)
Functional status

Loss of function of HIBCH mutants [mitochondrial matrix]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
3-hydroxyisobutryl-CoA hydrolase deficiency DOID:0060949 Methacrylic aciduria, Valine metabolic defect, HIBCH deficiency
Cross References
Mondo
Authored
Rothfels, K  (2024-07-29)
Reviewed
D'Eustachio, P  (2024-08-18)
Created
Rothfels, K  (2024-07-25)
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