Biochemistry · Topic
Mitochondrial NADH shuttles !
Glycolytic NADH cannot cross the inner membrane; two shuttles carry its electrons into the mitochondrion, with different ATP yields.
Updated 2026-11-01
Key facts
- Malate–aspartate: liver, kidney and heart; electrons arrive as matrix NADH and yield about 2.5 ATP.
- Glycerol-3-phosphate: skeletal muscle and brain; electrons arrive as FADH₂ at ubiquinone and yield about 1.5 ATP.
- That is why the total per glucose is given as 30 or 32 ATP depending on the shuttle.
- The malate–aspartate shuttle is reversible and needs transaminases (AST) with vitamin B6.
In detail
- Malate–aspartate, step 1: in the cytosol, malate dehydrogenase reduces oxaloacetate to malate using NADH.
- Step 2: malate enters the matrix on a carrier in exchange for α-ketoglutarate.
- Step 3: in the matrix, malate dehydrogenase oxidises it and regenerates NADH, which goes to complex I.
- Step 4: oxaloacetate is transaminated to aspartate, which leaves for the cytosol and becomes oxaloacetate again.
- Glycerol-3-phosphate: the cytosolic enzyme reduces dihydroxyacetone phosphate to glycerol-3-phosphate using NADH.
- Mitochondrial glycerol-3-phosphate dehydrogenase (GPD2, with FAD) on the outer face of the inner membrane passes the electrons to ubiquinone.
- Also called
- Malate–aspartate shuttle, Glycerol-3-phosphate shuttle
Clinical notes
- When the shuttles cannot keep up (intense exercise), cytosolic NADH is reoxidised by making lactate.
- The AST of the malate–aspartate shuttle is the same transaminase measured in liver tests.
Pathways
Related
- NAD⁺ (nicotinamide adenine dinucleotide)
- FAD (flavin adenine dinucleotide)
- Ubiquinone (coenzyme Q₁₀)
- Complex I (NADH dehydrogenase)
- Glycolysis
Test yourself
Think of the answer, then tap the question to see it.
Why do NADH shuttles exist?
The inner mitochondrial membrane is impermeable to NADH; the shuttles move only its electrons.
Which shuttle yields less ATP, and why?
The glycerol-3-phosphate shuttle: it delivers the electrons as FADH₂ to ubiquinone and skips complex I (about 1.5 ATP).
In which tissues does the malate–aspartate shuttle predominate?
In the liver, kidney and heart.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Malate-aspartate shuttle (Reactome, 2026); GPD2: Glycerol-3-phosphate dehydrogenase, mitochondrial (human) (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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Representative model, for educational purposes only.