General Information:

Id: 8,316
Diseases: Propionic acidemia - [OMIM]
Mammalia
review
Reference: Wongkittichote P et al.(2017) Propionyl-CoA carboxylase - A review Mol. Genet. Metab. 122: 145-152 [PMID: 29033250]

Interaction Information:

Comment Propionyl-CoA carboxylase is localized in mitochondria.
Formal Description
Interaction-ID: 84335

complex/PPI

Propionyl-CoA carboxylase

is localized in

cellular component

mitochondrion

Comment After translocation of PCCA into mitochondria, biotin is loaded onto lysine 669 by holocarboxylase synthase (E.C. 6.3.4.10)
Formal Description
Interaction-ID: 84336

complex/PPI

Propionyl-CoA carboxylase

interacts (colocalizes) with

drug/chemical compound

Biotin

Drugbank entries Show/Hide entries for
Comment PCCA null variants, such as R288X and S537X, result in the most severe phenotype of propionic acidemia.
Formal Description
Interaction-ID: 84343

gene/protein mutant

PCCA-p.R288X

increases_activity of

disease

Propionic acidemia

Comment PCCA null variants, such as R288X and S537X, result in the most severe phenotype of propionic acidemia.
Formal Description
Interaction-ID: 84344

gene/protein mutant

PCCA-p.S537X

increases_activity of

disease

Propionic acidemia

Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84356

gene/protein mutant

PCCB-p.A497V

NOT interacts (colocalizes) with

gene/protein

PCCA

Drugbank entries Show/Hide entries for PCCA
Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84357

gene/protein mutant

PCCB-p.R512C

NOT interacts (colocalizes) with

gene/protein

PCCA

Drugbank entries Show/Hide entries for PCCA
Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84358

gene/protein mutant

PCCB-p.L519P

NOT interacts (colocalizes) with

gene/protein

PCCA

Drugbank entries Show/Hide entries for PCCA
Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84359

gene/protein mutant

PCCB-p.W531X

NOT interacts (colocalizes) with

gene/protein

PCCA

Drugbank entries Show/Hide entries for PCCA
Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84360

gene/protein mutant

PCCB-p.A497V

decreases_activity of

complex/PPI

Propionyl-CoA carboxylase

Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84361

gene/protein mutant

PCCB-p.R512C

decreases_activity of

complex/PPI

Propionyl-CoA carboxylase

Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84362

gene/protein mutant

PCCB-p.L519P

decreases_activity of

complex/PPI

Propionyl-CoA carboxylase

Comment PCCB gene variants (A497V, R512C, L519P and W531X) disturb the interaction between PCCA and PCCB, resulting in non-functional propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84363

gene/protein mutant

PCCB-p.W531X

decreases_activity of

complex/PPI

Propionyl-CoA carboxylase

Comment Levels of methylcitrate and 3-hydroxypropionate are elevated in the urine of individuals with propionic acidemia.
Formal Description
Interaction-ID: 84364

disease

Propionic acidemia

increases_quantity of

drug/chemical compound

2-Methylcitrate

in urine
Comment Levels of methylcitrate and 3-hydroxypropionate are elevated in the urine of individuals with propionic acidemia.
Formal Description
Interaction-ID: 84365

disease

Propionic acidemia

increases_quantity of

drug/chemical compound

3-Hydroxypropanoate

in urine
Comment Methylcitrate is produced by conjugation of propionyl-CoA to oxaloacetate, a reaction thought to be catalyzed by citrate synthase.
Formal Description
Interaction-ID: 84367

drug/chemical compound

Propanoyl-CoA

increases_quantity of

drug/chemical compound

2-Methylcitrate

via conjugation to oxalacetate catalyzed by citrate synthase
Comment In patients with propionic acidemia and methylmalonic acidemia 3-hydroxypropionate is produced by beta-oxidation of propionic acid.
Formal Description
Interaction-ID: 84371

drug/chemical compound

Propanoate

increases_quantity of

drug/chemical compound

3-Hydroxypropanoate

via beta-oxidation
Comment Intracellular accumulation of propionyl-CoA inhibits mitochondrial metabolism and reduces the synthesis of citrate, GTP and ATP.
Formal Description
Interaction-ID: 84374

drug/chemical compound

Propanoyl-CoA

decreases_activity of

cellular component

mitochondrion

Comment Intracellular accumulation of propionyl-CoA inhibits mitochondrial metabolism and reduces the synthesis of citrate, GTP and ATP.
Formal Description
Interaction-ID: 84375

drug/chemical compound

Propanoyl-CoA

decreases_quantity of

drug/chemical compound

Citrate

Comment Intracellular accumulation of propionyl-CoA inhibits mitochondrial metabolism and reduces the synthesis of citrate, GTP and ATP.
Formal Description
Interaction-ID: 84376

drug/chemical compound

Propanoyl-CoA

decreases_quantity of

drug/chemical compound

ATP

Comment Intracellular accumulation of propionyl-CoA inhibits mitochondrial metabolism and reduces the synthesis of citrate, GTP and ATP.
Formal Description
Interaction-ID: 84377

drug/chemical compound

Propanoyl-CoA

decreases_quantity of

drug/chemical compound

GTP

Comment Propionyl-CoA carboxylase participates in anaplerotic replenishment of TCA intermediates as its product, methylmalonyl-CoA, ultimately contributes to the succinyl-CoA pool.
Formal Description
Interaction-ID: 84379

drug/chemical compound

Methylmalonyl-CoA

increases_quantity of

drug/chemical compound

Succinyl-CoA

Comment Alpha-ketoglutarate (2-Oxoglutarate), which is converted to succinyl-CoA, plays an important role in anaplerosis in the brain, given that the alpha-ketoglutarate pool contributes to production of GABA and glutamine.
Formal Description
Interaction-ID: 84380

drug/chemical compound

2-Oxoglutarate

increases_quantity of

drug/chemical compound

Succinyl-CoA

Comment Alpha-ketoglutarate (2-Oxoglutarate), which is converted to succinyl-CoA, plays an important role in anaplerosis in the brain, given that the alpha-ketoglutarate pool contributes to production of GABA and glutamine.
Formal Description
Interaction-ID: 84394

drug/chemical compound

2-Oxoglutarate

increases_quantity of

drug/chemical compound

Glutamine

Comment In patients with propionic acidemia the amount of glutamine/glutamate is decreased. This suggests deamination of those compounds to supply TCA substrates and support TCA function.
Formal Description
Interaction-ID: 84400

disease

Propionic acidemia

decreases_quantity of

drug/chemical compound

Glutamine

due to missing anaplerosis of succinyl-CoA via methylmalonyl-CoA
Comment In patients with propionic acidemia the amount of glutamine/glutamate is decreased. This suggests deamination of those compounds to supply TCA substrates and support TCA function.
Formal Description
Interaction-ID: 84408

disease

Propionic acidemia

decreases_quantity of

drug/chemical compound

Glutamate

due to missing anaplerosis of succinyl-CoA via methylmalonyl-CoA
Comment Alpha-ketoglutarate (2-Oxoglutarate), which is converted to succinyl-CoA, plays an important role in anaplerosis in the brain, given that the alpha-ketoglutarate pool contributes to production of GABA and glutamine.
Formal Description
Interaction-ID: 84412

drug/chemical compound

2-Oxoglutarate

increases_quantity of

drug/chemical compound

GABA

Comment Methylcitrate is produced by conjugation of propionyl-CoA to oxaloacetate, a reaction thought to be catalyzed by citrate synthase.
Formal Description
Interaction-ID: 84413

drug/chemical compound

Oxaloacetate

increases_quantity of

drug/chemical compound

2-Methylcitrate

in the presence of higher amounts of propionyl-CoA
Comment Propionyl-CoA was shown to inhibit isolated alpha-ketoglutarate (2-Oxoglutarate) dehydrogenase activity.
Formal Description
Interaction-ID: 84415

drug/chemical compound

Propanoyl-CoA

decreases_activity of

complex/PPI

Oxoglutarate dehydrogenase

Comment Propionate inhibits succinate ligase (GDP) activity.
Formal Description
Interaction-ID: 84416

drug/chemical compound

Propanoate

decreases_activity of

complex/PPI

Succinate-CoA ligase [GDP-forming]

Comment Methylcitrate has been implicated in dysfunction of citrate synthase and isocitrate dehydrogenase altering TCA cycle function.
Formal Description
Interaction-ID: 84417

drug/chemical compound

2-Methylcitrate

decreases_activity of

gene/protein

CS

Drugbank entries Show/Hide entries for CS
Comment Methylcitrate has been implicated in dysfunction of citrate synthase and isocitrate dehydrogenase altering TCA cycle function.
Formal Description
Interaction-ID: 84418

drug/chemical compound

2-Methylcitrate

decreases_activity of

gene/protein

IDH2

Drugbank entries Show/Hide entries for IDH2
Comment Methylcitrate has been implicated in dysfunction of citrate synthase and isocitrate dehydrogenase altering TCA cycle function.
Formal Description
Interaction-ID: 84419

gene/protein

CS

affects_activity of

process

tricarboxylic acid cycle

Drugbank entries Show/Hide entries for CS
Comment Methylcitrate has been implicated in dysfunction of citrate synthase and isocitrate dehydrogenase altering TCA cycle function.
Formal Description
Interaction-ID: 84420

gene/protein

IDH2

affects_activity of

process

tricarboxylic acid cycle

Drugbank entries Show/Hide entries for IDH2
Comment Propionyl-CoA was shown to inhibit isolated alpha-ketoglutarate (2-Oxoglutarate) dehydrogenase activity. Alpha-ketoglutarate dehydrogenase complex, is an enzyme of the TCA cycle, and catalyzes the conversion of alpha-ketoglutarate (2-oxoglutarate) to succinyl-CoA and CO2.
Formal Description
Interaction-ID: 84421

complex/PPI

Oxoglutarate dehydrogenase

decreases_quantity of

drug/chemical compound

2-Oxoglutarate

Comment Propionyl-CoA was shown to inhibit isolated alpha-ketoglutarate (2-Oxoglutarate) dehydrogenase activity. Alpha-ketoglutarate dehydrogenase complex, is an enzyme of the TCA cycle, and catalyzes the conversion of alpha-ketoglutarate (2-oxoglutarate) to succinyl-CoA and CO2.
Formal Description
Interaction-ID: 84422

complex/PPI

Oxoglutarate dehydrogenase

increases_quantity of

drug/chemical compound

Succinyl-CoA

Comment Increased glutamate level, due to a block in alpha-ketoglutarate dehydrogenase, leads to a decrease in heart muscle contractile function and this is improved with contribution from the propionate pathway through propionyl-CoA carboxylase activity.
Formal Description
Interaction-ID: 84423

drug/chemical compound

Glutamate

decreases_activity of

process

cardiac muscle contraction

in heart muscle; if glutamate is present in higher amounts
Comment Individuals with propionic acidemia have a higher glycine level.
Formal Description
Interaction-ID: 84424

disease

Propionic acidemia

increases_quantity of

drug/chemical compound

Glycine

in plasma
Drugbank entries Show/Hide entries for
Comment Propionyl-CoA as well as propionate inhibit pyruvate dehydrogenase, presumably due to alterations in propionyl-CoA/CoA ratios.
Formal Description
Interaction-ID: 84426

drug/chemical compound

Propanoyl-CoA

decreases_activity of

complex/PPI

Pyruvate dehydrogenase complex

in kidney, heart, liver
Comment Propionyl-CoA as well as propionate inhibit the pyruvate dehydrogenase, presumably due to alterations in propionyl-CoA/CoA ratios.
Formal Description
Interaction-ID: 84427

drug/chemical compound

Propanoate

decreases_activity of

complex/PPI

Pyruvate dehydrogenase complex

in kidney, heart, liver
Comment Propionyl-CoA inhibit carbamoyl phosphate synthase 1 (CPS1, E.C. 6.3.4.16) resulting in urea cycle dysfunction.
Formal Description
Interaction-ID: 84428

drug/chemical compound

Propanoyl-CoA

decreases_activity of

gene/protein

CPS1

Drugbank entries Show/Hide entries for CPS1
Comment Propionic acid, propionylcarnitine and methylcitrate can prevent normal function of the potassium channels of the heart (e.g. KCNH2) resulting in delayed re-polarization which can manifest as prolonged QTc.
Formal Description
Interaction-ID: 84429

drug/chemical compound

Propanoate

decreases_activity of

gene/protein

KCNH2

in heart
Drugbank entries Show/Hide entries for KCNH2
Comment Propionic acid, propionylcarnitine and methylcitrate can prevent normal function of the potassium channels of the heart (e.g. KCNH2) resulting in delayed re-polarization which can manifest as prolonged QTc.
Formal Description
Interaction-ID: 84430

drug/chemical compound

Propanoylcarnitine

decreases_activity of

gene/protein

KCNH2

in heart
Drugbank entries Show/Hide entries for KCNH2
Comment Propionic acid, propionylcarnitine and methylcitrate can prevent normal function of the potassium channels of the heart (e.g. KCNH2) resulting in delayed re-polarization which can manifest as prolonged QTc.
Formal Description
Interaction-ID: 84431

drug/chemical compound

2-Methylcitrate

decreases_activity of

gene/protein

KCNH2

in heart
Drugbank entries Show/Hide entries for KCNH2
Comment Propionic acid, propionylcarnitine and methylcitrate can prevent normal function of the potassium channels of the heart (e.g. KCNH2) resulting in delayed re-polarization which can manifest as prolonged QTc. This dysfunction may explain the cardiac arrhythmias observed in propionic acidemia.
Formal Description
Interaction-ID: 84432

disease

Propionic acidemia

increases_activity of

phenotype

irregular heartbeat

in heart
Comment Oxidative phosphorylation is disrupted in one of two propionic acidemia individuals.
Formal Description
Interaction-ID: 84433

disease

Propionic acidemia

decreases_activity of

process

oxidative phosphorylation

Comment Inflammation and ROS levels are elevated in individuals with propionic acidemia.
Formal Description
Interaction-ID: 84434

disease

Propionic acidemia

increases_quantity of

drug/chemical compound

Reactive oxygen species

in fibroblasts
Comment Inflammation and ROS levels are elevated in individuals with propionic acidemia.
Formal Description
Interaction-ID: 84435

disease

Propionic acidemia

increases_activity of

process

inflammatory response

in fibroblasts