Enzyme Kinetics: Michaelis‑Menten and Allosteric Regulation
Concept Name
Enzyme Kinetics
Genetic Loci
LDHA (11p15.1) encodes lactate dehydrogenase A – mutations cause exertional myoglobinuria. PYGM (11q13.1) encodes muscle glycogen phosphorylase – mutations cause McArdle disease (glycogen storage disease type V).
Intracellular Cascade
Michaelis‑Menten equation: V = Vmax[S]/(Km + [S]). Allosteric enzymes (e.g., PFK‑1) show sigmoidal kinetics and are regulated by positive effectors (AMP, fructose‑2,6‑bisphosphate) and negative effectors (ATP, citrate).
Required Cofactors
Many enzymes require cofactors: Mg²⁺ for kinase reactions, Zn²⁺ for carbonic anhydrase, NAD⁺/FAD for dehydrogenase reactions.
Histology Stains
Enzyme histochemistry for ATPase distinguishes muscle fiber types (Type I slow‑twitch = high ATPase at pH 9.4). Myophosphorylase staining is absent in McArdle disease.
EM Findings
Not applicable; enzyme kinetics is studied biochemically rather than ultrastructurally.
Knockout Phenotype
Knockout of LDH in mice impairs muscle performance during high‑intensity exercise due to inability to generate ATP via anaerobic glycolysis. PFKFB3 knockout reduces glycolysis in cancer cells and suppresses tumor growth.
Specific Toxins
Competitive inhibitors (e.g., statins vs HMG‑CoA reductase). Non‑competitive inhibitors (e.g., heavy metals binding sulfhydryl groups). Irreversible inhibitors (e.g., aspirin acetylation of COX‑1).