Signal Transduction & Hormones

BCH 100 — Introductory Biochemistry · Dr. Radi

build Jul 17 · 14:27 · CC BY-NC-SA 4.0 · owned figures (RDKit / matplotlib / PyMOL)
Dr. Radi

By the end of this unit, you can…

  • Classify hormones and the types of cell signaling (endocrine, paracrine, autocrine) and the water- vs lipid-soluble receptor logic
  • Explain second messengers (cAMP, Ca²⁺, IP₃/DAG) and how signal cascades amplify
  • Walk GPCR signaling through G proteins and adenylyl cyclase, and receptor tyrosine kinase (RTK) signaling
  • Connect hormonal control of metabolism — insulin, glucagon, epinephrine — and the biochemistry of diabetes
Dr. Radi

Today's route 🗺️

  1. Hormones & How They Signal
  2. Second Messengers & Amplification
  3. GPCRs — The G-Protein Switch
  4. Receptor Tyrosine Kinases
  5. Metabolic Hormones & Diabetes
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1 · Hormones & How They Signal

"A hormone is just a chemical message. What kind of message it is — and how a cell hears it — comes down to one thing: can it cross the membrane?"

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Three kinds of hormone

A hormone is a chemical messenger, and they come in three chemical families. Peptide/protein hormones (insulin, glucagon) are made of amino acids and are water-soluble — they can't cross the greasy membrane. Steroid hormones (cortisol, estrogen, testosterone) are built from cholesterol and are lipid-soluble — they slip right through. Amino-acid-derived hormones (epinephrine, thyroid hormone) are the mixed bag. That one property — water- vs. lipid-soluble — decides everything about how the message is delivered.

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How far does the message travel?

Signaling is sorted by distance. Endocrine signaling is long-range: a gland dumps the hormone into the bloodstream to reach distant targets (insulin from the pancreas acting on your whole body). Paracrine signaling is local — a cell talks to its neighbors (like the signals that coordinate inflammation). Autocrine signaling is a cell messaging itself (common in growth signals — and in cancer). Same molecule-and-receptor logic; three different ranges.

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Two ways a cell hears a hormone

Now the payoff of that solubility rule. A water-soluble hormone is stuck outside, so it binds a receptor on the cell surface, which triggers a second-messenger cascade inside — a fast response that needs no new proteins (this is the rest of the unit). A lipid-soluble hormone diffuses straight through the membrane, binds an intracellular receptor, and the pair goes to the nucleus to switch genes on or off — a slower response that makes new proteins. Fast switch vs. slow rewiring.

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2 · Second Messengers & Amplification

"The hormone never comes inside. It knocks at the door — and the cell relays that knock through a chain of couriers that turns one signal into millions."

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What "signal transduction" means

A water-soluble hormone can't get in — so how does its message? Through signal transduction: converting an outside signal into an inside action. It goes in three moves. Reception — the hormone (the first messenger) binds a surface receptor. Transduction — the receptor fires an internal relay that produces a second messenger. Response — that second messenger switches on enzymes and the cell acts. The hormone just knocks; everything after happens inside.

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The inside couriers

The "second messengers" are a small set of small molecules that carry the signal onward — and you should know four. cAMP, made from ATP by adenylyl cyclase, switches on protein kinase A (PKA). Ca²⁺, released from the ER, activates a whole roster of enzymes (usually via calmodulin). And a single membrane lipid, PIP₂, is split by phospholipase C into two messengers at once: IP₃, which opens ER calcium channels, and DAG, which activates protein kinase C (PKC).

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Amplification: one whisper, a shout

Here's the payoff of the relay. Every step multiplies. One hormone activates one receptor — but that receptor switches on ~10 G-proteins, each of which turns on an enzyme (adenylyl cyclase) that pumps out hundreds of cAMP, each of which fires a kinase that modifies thousands of target molecules. Down the chain, one hormone becomes millions of product molecules. That's why hormones work at nanomolar concentrations — a vanishingly small signal, enormously amplified.

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3 · GPCRs — The G-Protein Switch

"The most common receptor in your body, and the target of a third of all drugs, works like a molecular light switch — flicked on by a hormone and, crucially, timed to flick itself back off."

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The GPCR cascade

A G-protein-coupled receptor (GPCR) is a protein that snakes through the membrane seven times — it's the largest receptor family in your body. When a hormone binds the outside, the receptor changes shape and pokes a nearby G-protein, which swaps its GDP for GTP and switches ON. The activated Gα then turns on adenylyl cyclase, which converts ATP into cAMP — and cAMP fires up PKA, driving the cellular response. One binding event, a whole relay.

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How the signal gets switched OFF

A switch that only turns on is useless — so the system has two built-in off mechanisms. First, Gα is its own timer: it has a slow GTPase activity that hydrolyzes its GTP back to GDP, flipping itself off and reassembling with Gβγ. Second, the second messenger is destroyed — phosphodiesterase chops cAMP into plain AMP, so PKA goes quiet. Turn off the G-protein and clear the messenger, and the cell returns to baseline, ready for the next signal.

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When the off-switch is jammed: cholera

Here's what happens when that shut-off fails. Cholera toxin chemically modifies Gα so its GTPase can't work — it's stuck in the GTP, "on" state forever. Adenylyl cyclase never stops, cAMP floods the intestinal cells, and they pump out chloride and water without pause — producing the massive watery diarrhea that can kill by dehydration in a day. The entire deadly disease is nothing but a signal that can't turn off — which is exactly why the GTPase timer matters.

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4 · Receptor Tyrosine Kinases

"The other great receptor family doesn't use a G-protein at all. It pairs up, phosphorylates itself, and — instead of a quick metabolic tweak — reprograms the cell to grow."

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How an RTK switches on

A receptor tyrosine kinase (RTK) — the receptor for insulin and most growth factors — crosses the membrane just once and sits idle until a ligand binds. Then two receptors pair up (dimerize) and phosphorylate each other on tyrosines (autophosphorylation). Those phosphate tags recruit adapter proteins that launch a kinase cascade (Ras → MAPK), ending in the nucleus — switching on genes for growth and division.

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GPCR vs. RTK: two strategies

Step back and the two great receptor families make an instructive contrast. A GPCR threads the membrane seven times and works through a G-protein and second messengers — a fast, metabolic response measured in seconds (think epinephrine). An RTK crosses once, dimerizes, and signals by tyrosine phosphorylation through a kinase cascade — a slower response that usually reaches the nucleus to change gene expression (think insulin and growth factors). Quick tweak vs. deep rewiring.

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Why RTKs matter: growth and cancer

Because RTKs command growth and division, they're exactly the wires that go wrong in cancer. Normally an RTK only fires when its growth factor is present — but a mutation can lock one permanently ON, so the cell keeps dividing with no signal at all. That makes RTKs one of the biggest families of oncogenes — and also one of the best drug targets: a whole class of cancer therapies, the tyrosine-kinase inhibitors (like imatinib/Gleevec), work by blocking that phosphorylation and switching the runaway receptor back off.

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5 · Metabolic Hormones & Diabetes

"Everything in this unit comes together here: the hormones that hold your blood sugar steady are the GPCR and RTK systems you just learned — and diabetes is what happens when the signal breaks."

Dr. Radi

The glucose thermostat

Your blood glucose has to stay in a narrow band, and three hormones keep it there — two teams pulling opposite ways. After a meal, when glucose is high, the pancreas releases insulin, which tells cells to take glucose up and stash it as glycogen and fat — insulin lowers blood glucose. Between meals or under stress, when glucose is low, glucagon and epinephrine do the reverse: break down glycogen, run gluconeogenesis, and release fat — they raise blood glucose. Store vs. mobilize, holding the line.

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It's all the signaling you just learned

Here's the satisfying part: these metabolic hormones aren't new machinery — they're the exact receptor systems from this unit. Insulin works through a receptor tyrosine kinase (RTK) — which is why its effects include growth as well as glucose uptake. Glucagon and epinephrine work through GPCRs, raising cAMP to switch on the enzymes that break down glycogen and make glucose. Same two signaling strategies you met on the last two slides — now doing the most important homeostatic job in your body.

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Diabetes: when the signal fails

Diabetes is what happens when this glucose signal breaks — and it breaks in two ways. In Type 1, the immune system destroys the insulin-making β-cells, so there's little or no insulin at all — these patients must inject insulin. In Type 2 (far more common), the β-cells still make insulin, but the cells stop responding to it — insulin resistance — so glucose piles up despite plenty of hormone. Either way, blood glucose runs chronically high, slowly damaging eyes, kidneys, nerves, and blood vessels.

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Living with a broken thermostat

Because the body's automatic glucose control is gone, people with diabetes have to run the thermostat by hand — checking blood glucose (a drop of blood on a meter, or a continuous sensor) and dosing accordingly. Type 1 needs insulin, always. Type 2 is often managed first with diet and exercise and drugs like metformin (which curbs the liver's glucose output), adding insulin later if needed. It's biochemistry you can hold in your hand — a whole disease, and its treatment, written in one hormone's signal.

Blood-glucose testing: Tomwsulcer, CC0 (Wikimedia Commons)
Dr. Radi

Can you…?

  • ☐ classify hormones and the types of cell signaling (endocrine, paracrine, autocrine) and the water- vs lipid-soluble receptor logic?
  • ☐ explain second messengers (cAMP, Ca²⁺, IP₃/DAG) and how signal cascades amplify?
  • ☐ walk GPCR signaling through G proteins and adenylyl cyclase, and receptor tyrosine kinase (RTK) signaling?
  • ☐ connect hormonal control of metabolism — insulin, glucagon, epinephrine — and the biochemistry of diabetes?

If any box stays empty, the practice site has a drill for it. 🧪

Dr. Radi