Methylcrotonyl-CoA carboxylase

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methylcrotonoyl-CoA carboxylase
Identifiers
Ensembl

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UniProt

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a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human
Methylcrotonoyl-coenzyme A carboxylase 1 (alpha)
Identifiers
SymbolMCCC1
Chr. 3 q27.1
Search for
StructuresSwiss-model
DomainsInterPro
Methylcrotonoyl-coenzyme A carboxylase 2 (beta)
Identifiers
SymbolMCCC2
Chr. 5 q12-q13
Search for
StructuresSwiss-model
DomainsInterPro

Methylcrotonyl CoA carboxylase (

carbonyl group performing the fourth step in processing leucine, an essential amino acid.[1]

Structure

Gene

Human MCC is a

exons and resides on chromosome 5 at q12-q13.[4]

Protein

The enzyme contains α and β subunits. Human MCCCα is composed of 725

carboxylase.[6]

Function

During branched-chain amino acid degradation, MCC performs a single step in the breakdown of leucine to eventually yield acetyl CoA and acetoacetate.

acetyl CoA
.

Point mutations and deletion events in the genes coding for MCC can lead to

inborn error of metabolism which usually presents with vomiting, metabolic acidosis, very low plasma glucose concentration, and very low levels of carnitine in plasma.[9]

Diagram of leucine, HMB, and isovaleryl-CoA metabolism in humans
α-Ketoglutarate
Glutamate
Glutamate
Pyruvate
α-Ketoisocaproate
(α-KIC)
α-Ketoisocaproate
(α-KIC)
mitochondria
)
Excreted
in urine
(10–40%)


(
HMG-CoA
lyase
MC-CoA
carboxylase
HMG-CoA 
synthase
Unknown
enzyme
β-Hydroxybutyrate
Acetoacetate
Mevalonate
The image above contains clickable links
Human metabolic pathway for HMB and isovaleryl-CoA relative to L-leucine.[10][11][12] Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB.[10][11][12]

Mechanism

Bicarbonate is activated by the addition of

nucleophilic attack on the activated bicarbonate to form enzyme-bound carboxybiotin. The carboxybiotin portion of MCC can then undergo nucleophilic attack transferring the carboxyl group to the substrate, 3-methylcrotonyl CoA, to form 3-methylglutaconyl CoA.[7]

Regulation

MCC is covalently modified and inhibited by intermediates of

SIRT4 activates MCC and upregulates leucine catabolism by removing acyl residues that modified MCC.[13]

Clinical significance

In humans, MCC deficiency is a rare autosomal recessive genetic disorder whose clinical presentations range from benign to profound metabolic

convulsions or coma, that usually occurs between the age of 6-months to 3-years.[14]

Interactions

MCC has been shown to

Fusarium graminearum.[15]

References

  1. ISBN 978-0-13-017859-6
    .
  2. PMID 22264772
    .
  3. ^ "Entrez Gene:MCCC1 methylcrotonoyl-CoA carboxylase 1".
  4. ^ "Entrez Gene:MCCC2 methylcrotonoyl-CoA carboxylase 2".
  5. ^
    PMID 11406611
    .
  6. PMID 20725044
    .
  7. ^
    ISBN 0-7167-3051-0
    .
  8. PMID 17360195
    .
  9. ISBN 978-0-7216-4452-3
    .
  10. ^
    PMID 23374455
    .
  11. ^
    ISBN 978-0-12-387784-0. Retrieved 6 June 2016. Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds
    Figure 8.57: Metabolism of L-leucine
  12. PMID 28644956
    .
  13. S2CID 23446678
    .
  14. S2CID 29839939
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Methylcrotonyl-CoA_carboxylase&oldid=1170970183"