Biochemistry · College of Medicine & Health Sciences

Cellular
Respiration

The split. The bridge. The cycle. The power plant.

GlycolysisPDH complexTCA cycleETC & oxidative phosphorylation

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Four chapters · one goal

From glucose to ATP

01

The Split

Glycolysis

L.11
02

The Bridge

PDH complex

L.12
03

The Cycle

TCA cycle

L.13
04

The Power Plant

ETC & oxidative phosphorylation

L.10

Hover a chapter for its learning outcomes

The big picture

The journey of one glucose

01

The Split

Glycolysis

Glucose (6C) → 2 pyruvate (3C) · drag to rotate

Background · L.11.1

Glucose,
split in two

  • Oxidative breakdown: glucose → 2 pyruvate
  • Step 1 of aerobic respiration
  • Location: the cytosol

Transport · L.11.1

Getting glucose in

Two kinds of door

GLUT vs SGLT

Affinity decides who eats first

The GLUT family

Steps · L.11.2

Seven steps
to pyruvate

Drag to rotate · hover a station

Control enzymes · poisons

Who runs the line

L.11.5 · Blood glucose

Hexokinase vs glucokinase

L.11.4 · Energetics

Two ways to make ATP

L.11.3 · Fate of cytosolic NADH

No oxygen?
Make lactate.

  • Pyruvate → lactate (LDH)
  • Regenerates NAD⁺ → glycolysis continues
  • RBCs · avascular tissues · sprinting muscle

Clinical

Lactic acidosis

Red blood cells

Glycolysis in red cells

Regulation · L.11.2

Three levels of control

Critical thinking

Arsenate poisoning

Clinical · L.11.6

Pyruvate kinase
deficiency

  • 2nd most common enzyme-defect hemolytic anemia
  • ATP ↓ → Na+/K+ pump fails
  • K+ leaks out → cells shrink, spiculate
  • Spleen destroys them · 2,3-BPG ↑

Drag to rotate · hover the cell

Critical thinking

Why a fluoride tube?

  • Blood cells keep eating glucose in the tube
  • Fluoride blocks enolase → glycolysis stops
02

The Bridge

Pyruvate dehydrogenase complex

Background

Pyruvate needs
a bridge

  • With O2, pyruvate heads to the TCA cycle
  • Entry ticket: acetyl CoA
  • Glycolysis: cytosol
    PDH: mitochondrial matrix
  • So pyruvate must enter the matrix first

3 enzymes · 5 coenzymes

PDH complex

  • Multi-enzyme complex
  • Oxidative decarboxylation
  • Pyruvate (3C) → acetyl CoA (2C)
  • Releases CO2 + NADH
E1 · Decarboxylase E2 · Transacetylase E3 · Dehydrogenase

Schematic model · drag to rotate · hover to explore

5 coenzymes · the mnemonic

Tender Loving Care For Nobody

Localization · distribution

Where is PDH?

PDH complex analogues

Same machinery, different jobs

Clinical

PDH deficiency

  • ↑ Pyruvate, lactate, alanine
  • Congenital lactic acidosis
  • Progressive neurological signs

Clinical · vitamin B1

Thiamine deficiency

  • PDH & α-keto acid DH complexes fail
  • Energy failure in the hungriest tissues

Critical thinking

Thiamine before glucose. Why?

03

The Cycle

Citric acid cycle · TCA cycle · Krebs cycle

Citrate — the first product of the cycle · hover

Background

The central hub

  • Oxidizes acetyl CoA → CO2
  • Stage 2 of aerobic respiration · matrix
  • Amphibolic: breaks down & builds
  • Final common pathway for all fuels

Steps · L.13.1

One turn,
eight steps

Drag to rotate · hover an enzyme

Interactive

Fill in the cycle

control points · click any ?

Energetics

One turn = 10 ATP

Critical thinking

One glucose = how many ATP?

Regulation

Three control points

L.13.2 · L.13.3

Amphibolic hub

04

The Power Plant

Electron transport chain & oxidative phosphorylation

Vocabulary

Four terms to own

L.10.2 · Location

Electron
transport chain

  • Protein complexes in the inner membrane
  • Carries e−: NADH, FADH2 → O2
  • Released energy → ATP

Hover a membrane · drag to rotate

L.10.1 · Definition

Oxidative phosphorylation

L.10.2 · Components

Meet the chain

  1. INADH dehydrogenase
  2. IISuccinate dehydrogenase
  3. IIICytochrome bc1
  4. IVCytochrome c oxidase
  5. Q · cMobile carriers
  6. VATP synthase

Chemiosmotic theory · Peter Mitchell

Protons do
the work

  • e− flow down the chain
  • …pumps H+ out: 4 · 4 · 2
  • Gradient: ↓pH + charge outside
  • H+ flow back → ATP

Energetics

ATP per NADH & FADH2

Complex V · F1Fo-ATPase

ATP synthase

  • Fo · membrane · H+ channel + c-ring
  • F1 · matrix · α β γ δ ε · catalytic
  • H+ flow spins the rotor → ATP

Hover a subunit · drag to rotate

L.10.4

Three ways to stop the plant

1 · Site-specific inhibitors

Block the chain

Click an inhibitor

2 · ATP synthase inhibitor

Oligomycin

  • Binds the Fo domain
  • Blocks H+ re-entry to the matrix
  • ATP synthesis stops

3 · Uncouplers

Uncouplers

  • e− flow continues — no ATP
  • Inner membrane leaks H+
  • No proton-motive force
  • Energy → heat
2,4-Dinitrophenol Dicumarol Salicylate Uncoupling protein

Live lab

Poison the
power plant

Recap

The numbers to remember

Sources

References

Textbook

Lippincott Illustrated Reviews: Biochemistry

9th ed. · Abali, Cline, Franklin, Viselli · Wolters Kluwer

Ch. 6 Bioenergetics & oxidative phosphorylation (cited in L.10 as Ch. 5, pp. 85–94) · Ch. 8 Glycolysis, pp. 107–126 · Ch. 9 TCA cycle & PDH complex, pp. 127–135

Lecture · L.10

Oxidative phosphorylation & ETC

Dr. D. Vijaya Marakala, Associate Professor · COMHS, National University of Science & Technology

Lecture · L.11

Glycolysis

Transport, steps, regulation, anaerobic glycolysis & PK deficiency · COMHS, National University of Science & Technology

Lecture · L.12 – L.13

PDH complex & citric acid cycle

Reactions, regulation and energetics · COMHS, National University of Science & Technology

Supporting facts

Hover-card details

NCBI Bookshelf (StatPearls, GeneReviews) · PubMed Central · nobelprize.org

3D models are schematic teaching models, not atomic structures.