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[Biochemistry](https://durgical.com/en/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

- [Acute pancreatitis](https://durgical.com/en/conditions/acute-pancreatitis/)

## Related

- [Enzyme kinetics (Michaelis–Menten and Lineweaver–Burk)](https://durgical.com/en/biochemistry/topics/enzyme-kinetics/)
- [Types of enzyme inhibition](https://durgical.com/en/biochemistry/topics/types-of-enzyme-inhibition/)
- [Isoenzymes](https://durgical.com/en/biochemistry/topics/isoenzymes/)
- [Phosphofructokinase-1 (PFK-1)](https://durgical.com/en/biochemistry/enzymes/phosphofructokinase-1/)
- [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)
- [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/)
- [Pyruvate dehydrogenase complex (PDH)](https://durgical.com/en/biochemistry/enzymes/pyruvate-dehydrogenase-complex/)
- [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)
- [Carbamoyl phosphate synthetase I (CPS-I)](https://durgical.com/en/biochemistry/enzymes/carbamoyl-phosphate-synthetase-i/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Enzyme: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002353.htm) (MedlinePlus, US National Library of Medicine, 2026); [PYGM: Glycogen phosphorylase, muscle form (human)](https://www.uniprot.org/uniprotkb/P11217/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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