Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
Am. J. Hum. Genet. 59, 519-528 (1996)[PubMed:8751852]
Succinyl CoA: 3-oxoacid CoA transferase (SCOT; E.C.2.8.3.5) mediates the rate-determining step of ketolysis in extrahepatic tissues, the esterification of acetoacetate to CoA for use in energy production. Hereditary SCOT deficiency in humans causes episodes of severe ketoacidosis. We obtained human-heart SCOT cDNA clones spanning the entire 1,560-nt coding sequence. Sequence alignment of the human SCOT peptides with other known CoA transferases revealed several conserved regions of potential functional importance. A single approximately 3.2-kb SCOT mRNA is present in human tissues (heart > leukocytes >> fibroblasts), but no signal is detectable in the human hepatoma cell line HepG2. We mapped the human SCOT locus (OXCT) to the cytogenetic band 5p13 by in situ hybridization. From fibroblasts of a patient with hereditary SCOT deficiency, we amplified and cloned cDNA fragments containing the entire SCOT coding sequence. We found a homozygous C-to-G transversion at nt 848, which changes the Ser 283 codon to a stop codon. This mutation (S283X) is incompatible with normal enzyme function and represents the first documentation of a pathogenic mutation in SCOT deficiency.
Evidence
2:
Inferred from Mutant PhenotypeUniProtKB
The activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; EC 2.8.3.5) is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT deficiency causes episodic ketoacidosis. Here we describe the human SCOT gene, which spans more than 100 kb and contains 17 exons, on chromosome 5p13. We report pathogenic missense mutations in three SCOT-deficient patients designated GS04, 05, and 06. GS04 is a G219E/G324E compound; GS05 is a V221M homozygote, and GS06 is a G324E homozygote. We constructed a tertiary structural model of human SCOT by homology modeling based on the known structure of Acidaminococcus fermentans glutaconate CoA transferase. The model predicts that V221 and G219 are on the dimerizing surface, whereas G324 is near the active site. SCOT activity was reduced to a comparable degree in all three patients, but in a transient expression assay in SCOT-deficient fibroblasts, cDNAs containing G219E and G324E produced no detectable activity, whereas V221M constructs yielded approximately 10% of the control peptide level and detectable specific activity. Interestingly, GS05 had the mildest clinical course reported to date and detectable levels of SCOT protein in fibroblasts.
The activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; EC 2.8.3.5) is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT deficiency causes episodic ketoacidosis. Here we describe the human SCOT gene, which spans more than 100 kb and contains 17 exons, on chromosome 5p13. We report pathogenic missense mutations in three SCOT-deficient patients designated GS04, 05, and 06. GS04 is a G219E/G324E compound; GS05 is a V221M homozygote, and GS06 is a G324E homozygote. We constructed a tertiary structural model of human SCOT by homology modeling based on the known structure of Acidaminococcus fermentans glutaconate CoA transferase. The model predicts that V221 and G219 are on the dimerizing surface, whereas G324 is near the active site. SCOT activity was reduced to a comparable degree in all three patients, but in a transient expression assay in SCOT-deficient fibroblasts, cDNAs containing G219E and G324E produced no detectable activity, whereas V221M constructs yielded approximately 10% of the control peptide level and detectable specific activity. Interestingly, GS05 had the mildest clinical course reported to date and detectable levels of SCOT protein in fibroblasts.
The process whose specific outcome is the progression of adipose tissue over time, from its formation to the mature structure. Adipose tissue is specialized tissue that is used to store fat.
The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
The chemical reactions and pathways involving ketone bodies, any one of the three substances: acetoacetate, D-3-hydroxybutyrate (beta-hydroxybutyrate) or acetone, as carried out by individual cells. Although 3-hydroxybutyrate is not a ketone, it is classed as a ketone body because it exists in an equilibrium with acetoacetate. Ketone bodies may accumulate in excessive amounts in the body in starvation, diabetes mellitus or in other defects of carbohydrate metabolism.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
Succinyl-CoA:3-ketoacid CoA transferase (SCOT; EC 2.8.3.5; locus symbol OXCT) is the key enzyme of ketone body utilization. Hereditary SCOT deficiency (MIM 245050) causes episodes of severe ketoacidosis. We developed a transient expression system for mutant SCOT cDNAs, using immortalized SCOT-deficient fibroblasts. This paper describes and characterizes three missense mutations in two SCOT-deficient siblings from Japan. They are genetic compounds who inherited the mutation C456F (c1367 G-->T) from their mother. Their paternal allele contains two mutations in cis, T58M (c173 C-->T) and V133E (c398T-->A). Expression of SCOT cDNAs containing either V133E or C456F produces no detectable SCOT activity, whereas T58M is functionally neutral. T58M is a rare sequence variant not detected in 100 control Japanese alleles. In fibroblasts from the proband (GS02), in whom immunoblot demonstrated no detectable SCOT peptide, we measured an apparent residual SCOT activity of 20-35%. We hypothesize that the high residual SCOT activity in homogenates may be an artifact caused by use of the substrate, acetoacetyl-CoA by other enzymes. Expression of mutant SCOT cDNAs more accurately reflects the residual activity of SCOT than do currently available assays in cell or tissue homogenates.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an acid stimulus.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus.
The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
The chemical reactions and pathways resulting in the breakdown of ketones, a class of organic compounds that contain the carbonyl group, CO, and in which the carbonyl group is bonded only to carbon atoms. The general formula for a ketone is RCOR, where R and R are alkyl or aryl groups.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an activity stimulus.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a drug stimulus. A drug is a substance used in the diagnosis, treatment or prevention of a disease.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a starvation stimulus, deprivation of nourishment.
IEAOrtholog Compara
Enzymatic activity
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.8.3.5: Succinyl-CoA + a 3-oxo acid ⇄ succinate + a 3-oxoacyl-CoA.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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