Page last updated: 2024-10-24

(4S)-4-hydroxy-2-oxoglutarate aldolase activity

Definition

Target type: molecularfunction

Catalysis of the reaction:(4S)-4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate. [EC:4.1.3.42, GOC:hjd, PMID:1098660, PMID:1339418]

**(4S)-4-hydroxy-2-oxoglutarate aldolase activity** is a crucial enzymatic activity involved in the breakdown of (4S)-4-hydroxy-2-oxoglutarate, a key intermediate in the biosynthesis of several amino acids. This enzyme catalyzes a reversible aldol cleavage reaction, splitting (4S)-4-hydroxy-2-oxoglutarate into pyruvate and glyoxylate.

**Mechanism:**

The enzyme utilizes a catalytic mechanism involving a Schiff base intermediate. The active site of the enzyme contains a lysine residue that forms a Schiff base with the carbonyl group of (4S)-4-hydroxy-2-oxoglutarate. This Schiff base formation facilitates the cleavage of the carbon-carbon bond, resulting in the release of pyruvate and glyoxylate.

**Biological Importance:**

(4S)-4-hydroxy-2-oxoglutarate aldolase activity plays a significant role in various metabolic pathways, including:

* **Amino Acid Biosynthesis:** It is essential for the synthesis of L-lysine, L-threonine, and L-isoleucine.
* **Glyoxylate Cycle:** This enzyme contributes to the glyoxylate cycle, a metabolic pathway that allows organisms to utilize acetate as a carbon source for growth.
* **Degradation of Xenobiotics:** (4S)-4-hydroxy-2-oxoglutarate aldolase activity can be involved in the degradation of certain foreign compounds.

**Regulation:**

The activity of (4S)-4-hydroxy-2-oxoglutarate aldolase can be regulated by various factors, including:

* **Substrate Concentration:** The enzyme's activity is directly proportional to the concentration of (4S)-4-hydroxy-2-oxoglutarate.
* **pH:** The enzyme's activity is optimal at a specific pH range.
* **Inhibitors:** Specific inhibitors can bind to the active site and block the enzyme's activity.

**Clinical Relevance:**

Dysregulation of (4S)-4-hydroxy-2-oxoglutarate aldolase activity has been implicated in certain human diseases, including:

* **Lysinuric Protein Intolerance:** A genetic disorder characterized by a deficiency in this enzyme activity, leading to impaired lysine metabolism.
* **Cancer:** Altered enzyme activity has been observed in various cancers, potentially contributing to tumor growth and progression.

**Overall, (4S)-4-hydroxy-2-oxoglutarate aldolase activity is a crucial enzymatic function essential for a wide range of metabolic processes. Understanding its molecular mechanism, biological significance, and regulation is crucial for comprehending cellular metabolism and developing potential therapeutic strategies for related diseases.**'
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Proteins (2)

ProteinDefinitionTaxonomy
KHG/KDPG aldolaseA KHG/KDPG aldolase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A955]Escherichia coli K-12
4-hydroxy-2-oxoglutarate aldolase, mitochondrialA 4-hydroxy-2-oxoglutarate aldolase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86XE5]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
chelidamic acid
dipicolinic aciddipicolinic acid : A pyridinedicarboxylic acid carrying two carboxy groups at positions 2 and 6.pyridinedicarboxylic acidbacterial metabolite
2-keto-3-deoxy-6-phosphogluconate2-dehydro-3-deoxy-6-phospho-D-gluconic acid : The 5-phospho derivative of 2-dehydro-D-gluconic acid.

2-keto-3-deoxy-6-phosphogluconate: structure given in first source; an intermediate in glucose metabolism
ketoaldonic acid phosphateEscherichia coli metabolite