Phosphoenolpyruvate carboxykinase (EC 4.1.1.32, PEPCK) is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide. [1] [2] [3] It is found in two forms, cytosolic and mitochondrial.

There are four major pathways in which PEPCK plays a key role . These are ( a ) gluconeogenesis, ( b ) glyceroneogenesis, ( c ) the synthesis of serine, and ( d ) the conversion of the carbon skeletons of amino acids, such as glutamine and glutamate, to P-enolpyruvate (via PEPCK) and then to pyruvate (via pyruvate kinase) for subsequent ...

Phosphoenolpyruvate carboxykinase (PEPCK) is well known for its role in gluconeogenesis. However, PEPCK is also a key regulator of TCA cycle flux. The TCA cycle integrates glucose, amino acid and lipid metabolism depending on cellular needs.

Nov 1, 2021 · In this review, we summarize the metabolic and non-metabolic roles of the PCK enzyme in cells, especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK's expression, and discuss its clinical relevance.

In this third minireview, high-resolution crystal structures of mammalian PEPCK are examined to gain insights into the mechanism of PEPCK catalysis, including the reaction's reversibility and nucleotide specificity.

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a committed and rate-limiting step in hepatic gluconeogenesis, and its activity is tightly regulated to maintain normal blood glucose levels. PEPCK activity is primarily modulated through hormonal control of transcription [1–3].

In humans and other mammals, PCK is a central enzyme in carbohydrate metabolism, helping to regulate the blood glucose level. Gluconeogenic tissues, such as kidney and liver, convert lactate and other non-carbohydrate molecules to glucose, which in turn is released into the blood.

The metabolism of glucose to produce ATP is generally considered to be the primary stimulus for insulin release from beta-cells. Similarly, gluconeogenesis from phosphoenolpyruvate (PEP) is believed to be the primarily pathway via the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C).

Apr 4, 2025 · Sequencing analysis of plant PEPCK reveals that the N-terminal extension typically contains one or two potential phosphorylation sites (Kim & Smith, 1994). Light/dark transitions play a significant role in the phosphorylation of PEPCK, with the enzyme being phosphorylated in the dark and dephosphorylated in the light (Walker & Leegood, 1995 ...

In higher organisms, PEPCK isoforms are intricately regulated and activated through several physiological and pathological stimuli such as corticoids, hormones, nutrient starvation and hypoxia. Isoform-specific transcriptional/translational regulation and their interplay in maintaining glucose homeostasis remain to be fully understood.