Advanced BiologyCell Communication and Cell Cycle

Amplification and Changes in Pathways

Each activated enzyme in a cascade activates many of the next, so one ligand can trigger millions of product molecules. A mutated receptor or relay protein can block a response or switch it on for good.

Not started Jump to practice

A single hormone molecule can make a liver cell release millions of glucose molecules. The trick is the cascade you met in Reception, Transduction and Response: at each step, one active molecule switches on many of the next.

Change how many each molecule activates and how many steps there are.

Key idea

Amplification multiplies: if each step activates $g$ of the next, then after $n$ steps one signal gives $g^n$ product molecules. A mutation in a receptor or relay protein can block the whole response, or switch it on for good even with no signal.

Why it works

Why multiply and not add? Each active molecule in a row acts on its own share of the next row. If one receptor activates 10 G proteins, and each of those leads to 10 molecules of active enzyme, that is 10 groups of 10, or 100. One more step of 10 makes 10 groups of 100: 1,000. Adding (10 + 10 + 10 = 30) would count the molecules of only one branch at each step.

Worked examples

Worked example: A three-step cascade

A receptor activates 20 G proteins. Each leads to 100 cAMP. Each cAMP (through kinase A) leads to 50 active enzymes. How many active enzymes per signal molecule?
  1. Multiply the gains: $20 \times 100 \times 50$.
  2. $= 100{,}000$.

Answer: 100,000 active enzymes from one signal molecule.

Worked example: A stuck switch

Ras is a relay protein that passes on growth signals from a receptor tyrosine kinase. A mutation leaves Ras always in its active form. What happens to the cell?
  1. Normally Ras is active only after the receptor binds a growth factor, and then switches itself off.
  2. Stuck "on", it sends the divide signal all the time.
  3. The cell divides even without growth factor.

Answer: The cell keeps receiving a signal to divide: uncontrolled division, one of the steps toward cancer.

A pathway can fail in two ways: always on, or never on.

Common mistake

Adding the gains of the steps instead of multiplying them. If each step activates 10 of the next, three steps give $10 \times 10 \times 10 = 1{,}000$, not $10 + 10 + 10 = 30$. Check by sketching the first two rows: one molecule, then 10, then 10 more under each of those.

Amplification explains two facts about hormones. They work at tiny concentrations in the blood, because the cell multiplies each bound molecule many times over. And responses can be fast, because the cell does not have to make new proteins; it only switches on enzymes that are already there.

Amplification is also why pathways need off switches. Phosphatases remove phosphates from kinases, and an enzyme breaks cAMP down, so the response stops soon after the signal leaves the receptor.

Practice

Pass with 3 right answers, the last 2 in a row. Each right answer earns 3 XP.

Loading practice…

Builds on

Leads to

This is one of the top rungs of Advanced Biology (AP and College).

Sources and further reading

  • OpenStax, Biology 2e, 9.2 Propagation of the Signal
  • OpenStax, Biology 2e, 10.4 Cancer and the Cell Cycle
  • OpenStax, Biology for AP Courses, 9.2 Propagation of the Signal
@teddyrookbook GitHub