3-hydroxy-3-methylglutaryl-CoA lyase

3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase (hydroxymethylglutaricaciduria)
Identifiers
Symbol	HMGCL
Entrez	3155
HUGO	5005
OMIM	246450
RefSeq	NM_000191
UniProt	P35914
Other data
EC number	4.1.3.4
Locus	Chr. 1 p36.1-p35

3-hydroxy-3-methylglutaryl-CoA lyase (or HMG-CoA lyase) plays an essential role in breaking down dietary proteins and fats for energy.

Specifically, the enzyme is required for ketogenesis in the liver, and is also responsible for processing the amino acid leucine.

Pathology

Mutations in the HMGCL gene cause 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

External links

MeSH 3-hydroxy-3-methylglutaryl-coenzyme+A+lyase

Carbon-carbon lyases (EC 4.1)

4.1.1: Carboxy-lyases	Pyruvate decarboxylase · Oxaloacetate decarboxylase · Acetoacetate decarboxylase · Malonyl-CoA decarboxylase · Glutamate decarboxylase · Ornithine decarboxylase · Lysine decarboxylase · Phosphoribosylaminoimidazole carboxylase · Histidine decarboxylase · Uridine monophosphate synthetase/Orotidine 5'-phosphate decarboxylase · Aromatic L-amino acid decarboxylase · Phosphoenolpyruvate carboxylase · Pyrophosphomevalonate decarboxylase · Uroporphyrinogen III decarboxylase · RuBisCO · Phosphoenolpyruvate carboxykinase · Adenosylmethionine decarboxylase

4.1.2: Aldehyde-lyases	Aldolase (Aldolase A, Aldolase B, Aldolase C) · 2-hydroxyphytanoyl-CoA lyase · Threonine aldolase

4.1.3: Oxo-acid-lyases	3-hydroxy-3-methylglutaryl-CoA lyase

4.1.99: Other	Tryptophanase

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

Metabolism: lipid metabolism · ketones/cholesterol synthesis enzymes/steroid metabolism

Mevalonate pathway

To HMG-CoA	Acetyl-Coenzyme A acetyltransferase · HMG-CoA synthase (regulated step)

Ketogenesis	HMG-CoA lyase · 3-hydroxybutyrate dehydrogenase · Thiophorase

To Mevalonic acid	HMG-CoA reductase

To DMAPP	Mevalonate kinase · Phosphomevalonate kinase · Pyrophosphomevalonate decarboxylase · Isopentenyl-diphosphate delta isomerase

Geranyl-	Dimethylallyltranstransferase · Geranyl pyrophosphate

To cholesterol

To lanosterol	Farnesyl-diphosphate farnesyltransferase · Squalene monooxygenase · Lanosterol synthase

7-Dehydrocholesterol path	Lanosterol 14α-demethylase · Sterol-C5-desaturase-like · 7-Dehydrocholesterol reductase

Desmosterol path	24-dehydrocholesterol reductase

To Bile acids

Cholesterol 7α-hydroxylase · Sterol 27-hydroxylase

aldosterone: 18-hydroxylase

cortisol/cortisone: 17α-hydroxylase · 11β dehydrogenase (HSD11B1, HSD11B2)

both: 3β dehydrogenase · 21α-hydroxylase · 11β-hydroxylase

To sex hormones

To androgens	17α-hydroxylase/17,20 lyase · 3β dehydrogenase · 17β dehydrogenase · 5α reductase (1,2)

To estrogens	Aromatase

Other/ungrouped

Steroid metabolism: sulfatase (Steroid sulfatase) · sulfotransferase (SULT1A1, SULT2A1)

Steroidogenic acute regulatory protein

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

M: END

anat/phys/devp/horm

noco(d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

Metabolism: amino acid metabolism · synthesis and catabolism enzymes (essential in CAPS)

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase · Glutaryl-CoA dehydrogenase

LEUCINE→	Branched chain aminotransferase · Branched-chain alpha-keto acid dehydrogenase complex · Isovaleryl coenzyme A dehydrogenase · Methylcrotonyl-CoA carboxylase · Methylglutaconyl-CoA hydratase · 3-hydroxy-3-methylglutaryl-CoA lyase

TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase · Arylformamidase · Kynureninase · 3-hydroxyanthranilate oxidase · Aminocarboxymuconate-semialdehyde decarboxylase · Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase · Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase · Creatine kinase

alanine→	Alanine transaminase

cysteine→	D-cysteine desulfhydrase

threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate


HISTIDINE→	Histidine ammonia-lyase · Urocanate hydratase · Formiminotransferase cyclodeaminase

proline→	Proline oxidase · Pyrroline-5-carboxylate reductase · 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 · PYCR1

arginine→	Ornithine aminotransferase · Ornithine decarboxylase · Agmatinase

→alpha-ketoglutarate→TCA	Glutamate dehydrogenase

Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase · Glutathione synthetase · Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase · Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched chain aminotransferase · Branched-chain alpha-keto acid dehydrogenase complex · Enoyl-CoA hydratase · 3-hydroxyisobutyryl-CoA hydrolase · 3-hydroxyisobutyrate dehydrogenase · Methylmalonate semialdehyde dehydrogenase

ISOLEUCINE→	Branched chain aminotransferase · Branched-chain alpha-keto acid dehydrogenase complex · 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→	generation of homocysteine: Methionine adenosyltransferase · Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase · Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase · Cystathionine gamma-lyase

THREONINE→	Threonine aldolase

→succinyl-CoA→TCA	Propionyl-CoA carboxylase · Methylmalonyl CoA epimerase · Methylmalonyl-CoA mutase

G→fumarate


PHENYLALANINE→tyrosine→	Phenylalanine hydroxylase · Tyrosine aminotransferase · 4-Hydroxyphenylpyruvate dioxygenase · Homogentisate 1,2-dioxygenase · Fumarylacetoacetate hydrolase tyrosine→melanin: Tyrosinase

G→oxaloacetate


asparagine→aspartate→	Asparaginase/Asparagine synthetase · Aspartate transaminase

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)