Biochemistry pathways and cycles in short understanding way
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Here is a complete, concise guide to all major biochemistry pathways and cycles, sourced from Lippincott Illustrated Reviews: Biochemistry, Harper's Illustrated Biochemistry, Basic Medical Biochemistry, and Mulholland & Greenfield's Surgery.
Biochemistry Pathways & Cycles - Short Understanding Guide
1. Glycolysis
"Glucose → Pyruvate"
Location: Cytoplasm (all cells)
Purpose: Generate ATP from glucose; works with or without oxygen
Two phases:
- Phase I (Preparatory): Glucose → Fructose 1,6-bisphosphate. Spends 2 ATP
- Phase II (ATP-generating): Fructose 1,6-bisphosphate → 2 Pyruvate. Generates 4 ATP + 2 NADH
- Net yield: 2 ATP + 2 NADH per glucose
3 irreversible (rate-limiting) enzymes:
- Hexokinase/Glucokinase
- Phosphofructokinase-1 (PFK-1) - the KEY regulator
- Pyruvate kinase
Pyruvate fate:
- With O₂ → acetyl-CoA (enters TCA cycle)
- Without O₂ → Lactate (lactic acid fermentation; regenerates NAD⁺)
2. Citric Acid Cycle (TCA / Krebs Cycle)
"Acetyl-CoA → CO₂ + energy carriers"
Location: Mitochondrial matrix
Purpose: Main ATP-generating hub; oxidizes acetyl-CoA completely
The loop in simple terms:
- Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C)
- Citrate is processed through 8 steps, releasing 2 CO₂
- Oxaloacetate is regenerated to keep the cycle going
Per turn yields:
| Product | Amount |
|---|---|
| NADH | 3 |
| FADH₂ | 1 |
| GTP/ATP | 1 |
| CO₂ | 2 |
- Total: ~10 ATP equivalents per turn (via oxidative phosphorylation)
- The cycle also feeds gluconeogenesis, amino acid synthesis, heme synthesis, and fatty acid synthesis
Key concept - Anaplerosis: Adding carbon to the cycle (e.g., pyruvate → oxaloacetate). Cataplerosis: Removing carbon from the cycle. Both must be equal to sustain the cycle.
3. Oxidative Phosphorylation (Electron Transport Chain)
"NADH/FADH₂ → ATP"
Location: Inner mitochondrial membrane
Purpose: Convert reducing equivalents (NADH, FADH₂) into ATP using oxygen
Flow: NADH/FADH₂ → Complex I/II → Ubiquinone (Q) → Complex III → Cytochrome c → Complex IV → O₂ → H₂O
- NADH yields ~2.5 ATP
- FADH₂ yields ~1.5 ATP
- Total from 1 glucose (complete oxidation): ~30-32 ATP
Key concept: The proton gradient across the inner mitochondrial membrane drives ATP synthase (Complex V). This is called the chemiosmotic mechanism.
Important: If oxygen is absent (anaerobiosis), the chain stops and cells rely only on glycolysis.
4. Gluconeogenesis
"Non-glucose → Glucose"
Location: Mainly liver (also kidney, intestinal epithelium)
Purpose: Maintain blood glucose during fasting when glycogen stores fall
Substrates (gluconeogenic precursors):
- Lactate (from muscle)
- Glycerol (from fat breakdown)
- Amino acids (from protein, especially alanine and glutamine)
Key point: NOT the reverse of glycolysis. Three irreversible glycolysis steps are bypassed by different enzymes:
- Pyruvate carboxylase + PEPCK (bypass pyruvate kinase)
- Fructose-1,6-bisphosphatase (bypass PFK-1)
- Glucose-6-phosphatase (bypass hexokinase) - only in liver/kidney/intestine
Cost: Energy-expensive: uses 6 ATP equivalents per glucose made.
5. Glycogenesis & Glycogenolysis
"Glucose ↔ Glycogen (storage)"
Location: Liver and muscle
Glycogenesis (storage)
Glucose → Glucose-6-phosphate → Glucose-1-phosphate → UDP-glucose → Glycogen chain (via glycogen synthase)
- Costs 1 ATP per glucose stored
- Storage is ~97% efficient
Glycogenolysis (release)
Glycogen → Glucose-1-phosphate → Glucose-6-phosphate
- Enzyme: Glycogen phosphorylase (activated by glucagon/epinephrine via cAMP cascade)
- Glucose-6-phosphatase then releases free glucose (only in liver/kidney/intestine - NOT in muscle)
- Triggered by low blood glucose, exercise, or stress
6. Beta-Oxidation of Fatty Acids
"Fatty acids → Acetyl-CoA"
Location: Mitochondrial matrix (peroxisomes for very long-chain FAs)
Purpose: Break down fatty acids to fuel the TCA cycle; major energy source during fasting
Steps (per cycle, removes 2 carbons as acetyl-CoA):
- Activation: Fatty acid → Fatty acyl-CoA (costs 2 ATP)
- Transport into mitochondria via carnitine shuttle (rate-limiting step)
- Repeated cycles: each produces 1 acetyl-CoA + 1 NADH + 1 FADH₂
Example - Palmitate (16C): 7 rounds → 8 acetyl-CoA → ~106 ATP net
Key regulation: Malonyl-CoA (the first intermediate of FA synthesis) inhibits the carnitine shuttle - so FA synthesis and oxidation don't run simultaneously.
7. Fatty Acid Synthesis
"Acetyl-CoA → Fatty acids"
Location: Cytoplasm (liver, adipose, mammary gland)
Purpose: Store excess energy as fat
Key points:
- Acetyl-CoA must first exit mitochondria as citrate (citrate shuttle)
- Acetyl-CoA → Malonyl-CoA (by acetyl-CoA carboxylase - rate-limiting; activated by insulin)
- Fatty acid synthase (FAS) adds 2C units at a time
- Requires NADPH (supplied by pentose phosphate pathway)
- End product: Palmitate (16:0)
Remember: Opposite of beta-oxidation but uses different enzymes, different location, different cofactors.
8. Urea Cycle
"NH₃ → Urea (detox)"
Location: Liver - partly mitochondria, partly cytosol
Purpose: Convert toxic ammonia (from amino acid catabolism) into urea for urinary excretion
5 steps (mnemonic: "Ordinarily, Careless Crappers Are Also Frivolous About Urination"):
| Step | Compound | Location |
|---|---|---|
| 1 | NH₃ + HCO₃⁻ → Carbamoyl phosphate | Mitochondria |
| 2 | Carbamoyl phosphate + Ornithine → Citrulline | Mitochondria |
| 3 | Citrulline + Aspartate → Argininosuccinate | Cytosol |
| 4 | Argininosuccinate → Arginine + Fumarate | Cytosol |
| 5 | Arginine → Ornithine + Urea | Cytosol |
Key facts:
- 1 nitrogen from NH₃, 1 nitrogen from aspartate
- Carbon and oxygen of urea come from CO₂ (as HCO₃⁻)
- Rate-limited by CPS I (requires N-acetylglutamate as activator)
- Ornithine regenerates - just like oxaloacetate in TCA
- Defects cause hyperammonemia (toxic to brain)
9. Pentose Phosphate Pathway (HMP Shunt)
"Glucose-6-P → NADPH + Ribose-5-P"
Location: Cytoplasm (liver, RBCs, adrenal glands, mammary tissue)
Purpose: Produce NADPH (for reductive biosynthesis and antioxidant defense) and ribose-5-phosphate (for nucleotide synthesis)
Two branches:
- Oxidative branch: Produces NADPH (irreversible)
- Non-oxidative branch: Produces ribose-5-phosphate; reversible, connects to glycolysis
Clinical link: G6PD deficiency → insufficient NADPH → can't regenerate glutathione → RBCs susceptible to oxidative hemolysis
10. Ketone Body Synthesis & Use (Ketogenesis)
"Excess acetyl-CoA → Ketone bodies"
Location: Liver mitochondria (synthesis); extrahepatic tissues (use)
Purpose: Alternative fuel during prolonged fasting/starvation, especially for brain
Ketone bodies:
- Acetoacetate
- Beta-hydroxybutyrate (main form in blood)
- Acetone (exhaled)
Key point: Liver makes ketones but CANNOT use them (lacks thiophorase/succinyl-CoA transferase). Brain, heart, and muscle use them instead.
Big Picture: How the Pathways Connect
Diet (glucose, fats, proteins)
|
GLYCOLYSIS
Glucose → Pyruvate → Acetyl-CoA
|
┌────────────── TCA CYCLE ──────────────┐
| NADH / FADH₂ produced |
| ↓ |
| OXIDATIVE PHOSPHORYLATION |
| ATP !!! |
└────────────────────────────────────────┘
Fasting state:
Glycogen → Glucose (glycogenolysis)
OAA, lactate, amino acids → Glucose (gluconeogenesis)
Fatty acids → Acetyl-CoA (beta-oxidation) → TCA
Excess acetyl-CoA → Ketone bodies (brain fuel)
Quick Reference Table
| Pathway | Location | Main Input | Main Output | Key Enzyme |
|---|---|---|---|---|
| Glycolysis | Cytosol | Glucose | Pyruvate, 2 ATP | PFK-1 |
| TCA Cycle | Mitochondria | Acetyl-CoA | NADH, FADH₂, CO₂ | Isocitrate DH |
| Oxid. Phosph. | Inner mito. membrane | NADH/FADH₂ | ~30 ATP | ATP synthase |
| Gluconeogenesis | Liver/Kidney | Lactate/AA/Glycerol | Glucose | PEPCK |
| Glycogenesis | Liver/Muscle | Glucose | Glycogen | Glycogen synthase |
| Glycogenolysis | Liver/Muscle | Glycogen | Glucose | Glycogen phosphorylase |
| Beta-oxidation | Mitochondria | Fatty acids | Acetyl-CoA | Acyl-CoA DH |
| FA Synthesis | Cytosol | Acetyl-CoA | Palmitate | Acetyl-CoA carboxylase |
| Urea Cycle | Liver (mito+cytosol) | NH₃, Aspartate | Urea | CPS I |
| PPP (HMP shunt) | Cytosol | Glucose-6-P | NADPH, Ribose-5-P | G6PD |
| Ketogenesis | Liver mitochondria | Acetyl-CoA | Ketone bodies | HMG-CoA synthase |
Sources: Lippincott Illustrated Reviews: Biochemistry 8e; Harper's Illustrated Biochemistry 32e; Basic Medical Biochemistry - A Clinical Approach 6e; Mulholland & Greenfield's Surgery 7e
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Biochemistry Flashcards
PDF Document · PDF
What's inside - 33 cards across 10 pathways:
| Pathway | Cards | Colour |
|---|---|---|
| Glycolysis | 6 | Blue |
| TCA Cycle | 6 | Green |
| Oxidative Phosphorylation | 3 | Navy |
| Gluconeogenesis | 3 | Red |
| Glycogen Metabolism | 2 | Purple |
| Beta-Oxidation | 3 | Orange |
| Fatty Acid Synthesis | 2 | Teal |
| Urea Cycle | 3 | Red |
| Pentose Phosphate Pathway | 2 | Green |
| Ketone Body Metabolism | 2 | Orange |
Key intermediates covered: G6P, F-1,6-BP, Pyruvate, DHAP, 1,3-BPG, PEP, Acetyl-CoA, Citrate, Isocitrate, α-KG, Succinyl-CoA, OAA, Fumarate, NADH, FADH₂, Lactate, Glycerol, Alanine, UDP-Glucose, Malonyl-CoA, Carnitine, NH₃, Citrulline, Ornithine, Ribose-5-P, HMG-CoA, Acetoacetate, and more.
Each card shows the QUESTION (the intermediate) on top and the ANSWER / FATE below - cover the bottom half to quiz yourself.
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