Biochemistry · Topic
Allosteric and covalent regulation of enzymes !
The cell switches its enzymes on and off within seconds using molecules that bind outside the active site or chemical changes such as phosphorylation.
Updated 2026-11-01
Key facts
- Allosteric enzyme: has regulatory sites separate from the active site; usually multimeric, with a sigmoidal v-versus-[S] curve.
- Positive effectors stabilise the R form (relaxed, active) and negative ones the T form (tense, inactive). Example: PFK-1 (+ AMP, fructose 2,6-bisphosphate; − ATP, citrate).
- Reversible covalent modification: kinases add phosphate to Ser, Thr or Tyr and phosphatases remove it; the effect depends on the enzyme.
- Glucagon and adrenaline (cAMP → PKA) activate glycogen phosphorylase and inactivate glycogen synthase; insulin activates phosphatases and does the reverse.
- Proteolytic activation (zymogens): trypsinogen → trypsin by enteropeptidase; clotting factors are activated the same way.
In detail
- Homotropic effects: the substrate itself is the effector (cooperativity); heterotropic: another molecule regulates the enzyme.
- K-type enzymes change their Km (the curve shifts left or right); V-type enzymes change their Vmax.
- Allosteric control usually acts on the committed step of a pathway, and the end product slows it (negative feedback).
- More examples: acetyl-CoA carboxylase is activated by citrate and slowed by palmitoyl-CoA; urea-cycle CPS-I needs N-acetylglutamate.
- PDH is switched off when PDH kinase phosphorylates it (stimulated by ATP, NADH and acetyl-CoA) and switched on when a phosphatase removes the phosphate.
- Other covalent changes: acetylation, ADP-ribosylation (cholera and diphtheria toxins), γ-carboxylation (vitamin K–dependent clotting factors), ubiquitination.
- Control by enzyme amount (gene induction and repression) is slower: hours or days, versus seconds or minutes for allosteric and covalent control.
- Also called
- Allostery, Phosphorylation, Zymogens
Clinical notes
- In acute pancreatitis, trypsin is activated too early inside the pancreas and sets off the activation of the other enzymes (autodigestion).
- Haemoglobin is the classic allosteric protein: 2,3-BPG, CO₂ and H⁺ stabilise the T form and help O₂ delivery.
- Many cancer drugs inhibit kinases (for example the BCR-ABL kinase in chronic myeloid leukaemia).
Related conditions
Related
- Enzyme kinetics (Michaelis–Menten and Lineweaver–Burk)
- Types of enzyme inhibition
- Isoenzymes
- Phosphofructokinase-1 (PFK-1)
- Glycogen phosphorylase
- Glycogen synthase
- Pyruvate dehydrogenase complex (PDH)
- Acetyl-CoA carboxylase (ACC)
- Carbamoyl phosphate synthetase I (CPS-I)
- Hemoglobin and 2,3-BPG
Test yourself
Think of the answer, then tap the question to see it.
What shape is the rate curve of an allosteric enzyme?
Sigmoidal: substrate binding to one subunit makes binding to the others easier (cooperativity).
How does glucagon affect glycogen synthase and phosphorylase?
Through cAMP and PKA it phosphorylates them: phosphorylase is activated and synthase inactivated, so the liver releases glucose.
What is a zymogen?
An inactive form of an enzyme that is activated by cutting off part of the chain, such as trypsinogen becoming trypsin.
Which allosteric effector is the strongest activator of PFK-1?
Fructose 2,6-bisphosphate, which also inhibits fructose 1,6-bisphosphatase.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Enzyme: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); PYGM: Glycogen phosphorylase, muscle form (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.