Citrate synthase

Citrate synthase (<a href="/facts/Enzyme_Commission_number/Y5GNLRKX">E.C.</a> 2.3.3.1 (previously 4.1.3.7)) is an <a href="/facts/Enzyme/DSI1Fh7y">enzyme</a> that exists in nearly all living cells. It functions as a pace-making enzyme in the first step of the <a href="/facts/Citric_acid_cycle/EGJL9NXP">citric acid cycle</a> (or <a href="/facts/Krebs_cycle/EGJL9NXP">Krebs cycle</a>). Citrate synthase is located within <a href="/facts/Eukaryotic/SkwyPLMA">eukaryotic</a> cells in the <a href="/facts/Mitochondrial_matrix/tgC0ENLv">mitochondrial matrix</a>, but is encoded by nuclear <a href="/facts/DNA/nB89Iauz">DNA</a> rather than mitochondrial. It is synthesized using cytoplasmic <a href="/facts/Ribosomes/CF2u2gtg">ribosomes</a>, then transported into the mitochondrial matrix.
Citrate synthase is commonly used as a quantitative enzyme marker for the presence of intact <a href="/facts/Mitochondria/ErHqrdJ1">mitochondria</a>. Maximal activity of citrate synthase indicates the mitochondrial content of skeletal muscle. The maximal activity can be increased by <a href="/facts/Endurance_training/e7tRhK8T">endurance training</a> or <a href="/facts/High-intensity_interval_training/vNfuDGVB">high-intensity interval training</a>, with high-intensity interval training having the greater effect.
Citrate synthase <a href="/facts/Catalysis/LPBS7TQC">catalyzes</a> the <a href="/facts/Condensation_reaction/wMG0F6La">condensation reaction</a> of the two-carbon <a href="/facts/Acetate/U90VVczy">acetate</a> residue from <a href="/facts/Acetyl_coenzyme_A/XyxFfC84">acetyl coenzyme A</a> and a molecule of four-carbon <a href="/facts/Oxaloacetate/ojLoQw81">oxaloacetate</a> to form the six-carbon <a href="/facts/Citrate/EgKGQBdl">citrate</a>:

<ul><li><a href="/facts/Acetyl-CoA/XyxFfC84">acetyl-CoA</a> + oxaloacetate + <a href="/facts/H2O/0lkXnJPK">H2O</a> → citrate + <a href="/facts/Coenzyme_A/loAfeGpx">CoA-SH</a></li></ul>

Oxaloacetate is regenerated after the completion of one round of the Krebs cycle.
Oxaloacetate is the first substrate to bind to the enzyme. This induces the enzyme to change its conformation, and creates a binding site for the acetyl-CoA. Only when this citryl-CoA has formed will another conformational change cause thioester <a href="/facts/Hydrolysis/JTvwIHPs">hydrolysis</a> and release coenzyme A. This ensures that the energy released from the thioester bond cleavage will drive the condensation.

Citrate synthase open-in-new

Citrate synthase