Biochemistry · Short notes

Carbohydrate Metabolism: Short Notes & Cheat Sheet

Glycolysis, the TCA cycle and oxidative phosphorylation, gluconeogenesis, glycogen metabolism, the HMP shunt and related disorders.

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Short notes

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From glucose to ATP

Most ATP is made at the end, by oxidative phosphorylation; glycolysis gives only 2 ATP net.

Glycolysis and the link reaction

Glycolysis happens in the cytoplasm and turns one glucose into two pyruvate, with a net gain of 2 ATP and 2 NADH.
Regulatory enzymes: hexokinase (glucokinase in liver), phosphofructokinase-1 (the rate-limiting step) and pyruvate kinase.
Without oxygen, and always in red cells (which have no mitochondria), pyruvate becomes lactate.
Pyruvate dehydrogenase converts pyruvate to acetyl-CoA. It needs thiamine (B1), lipoic acid, CoA (B5), FAD (B2) and NAD (B3).

TCA cycle and ATP production

The TCA (Krebs) cycle runs in the mitochondrial matrix. Each acetyl-CoA yields 3 NADH, 1 FADH₂, 1 GTP and 2 CO₂.
The electron transport chain on the inner mitochondrial membrane makes about 2.5 ATP per NADH and 1.5 ATP per FADH₂.
Complete oxidation of one glucose gives about 30–32 ATP (older textbooks say 36–38).
Inhibitors: rotenone (complex I), antimycin A (complex III), cyanide and carbon monoxide (complex IV), oligomycin (ATP synthase). Uncouplers such as 2,4-dinitrophenol produce heat instead of ATP.

Gluconeogenesis and glycogen

Gluconeogenesis (liver and kidney) makes glucose from lactate (Cori cycle), alanine, glycerol and propionate, but not from even-chain fatty acids.
Its bypass enzymes: pyruvate carboxylase (needs biotin), PEP carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase.
Muscle lacks glucose-6-phosphatase, so muscle glycogen cannot supply blood glucose.
Glycogen synthase (stimulated by insulin) and glycogen phosphorylase (stimulated by glucagon and adrenaline) are the rate-limiting enzymes.
Glycogen storage diseases: von Gierke (type I, glucose-6-phosphatase), Pompe (type II, lysosomal acid maltase; affects the heart), McArdle (type V, muscle phosphorylase).

HMP shunt and sugar disorders

The pentose phosphate (HMP) pathway produces NADPH (for fatty acid and steroid synthesis and for keeping glutathione reduced) and ribose-5-phosphate.
G6PD is its rate-limiting enzyme. In G6PD deficiency, oxidant drugs (primaquine, dapsone, sulfonamides, nitrofurantoin) and fava beans cause haemolysis.
Galactosaemia is caused by GALT deficiency, and hereditary fructose intolerance by aldolase B deficiency.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Rate-limiting enzymes

Pathway	Enzyme
Glycolysis	Phosphofructokinase-1
TCA cycle	Isocitrate dehydrogenase
Gluconeogenesis	Fructose-1,6-bisphosphatase
Glycogen synthesis	Glycogen synthase
Glycogen breakdown	Glycogen phosphorylase
HMP shunt	Glucose-6-phosphate dehydrogenase

Energy yield

Step	Yield
Glycolysis (net)	2 ATP + 2 NADH
Pyruvate → acetyl-CoA (×2)	2 NADH
TCA cycle (×2)	6 NADH, 2 FADH₂, 2 GTP
Per NADH / FADH₂	≈ 2.5 / 1.5 ATP
Total per glucose	≈ 30–32 ATP

Memory aids

PDH needs 'Tender Loving Care For Nancy': Thiamine, Lipoic acid, CoA, FAD, NAD: the five cofactors of pyruvate dehydrogenase.

Exam traps

Red blood cells rely on glycolysis alone because they have no mitochondria.
Acetyl-CoA from even-chain fatty acids cannot be turned into glucose.
Pompe disease is a lysosomal disorder and mainly affects the heart.
G6PD deficiency causes haemolysis because red cells cannot make enough NADPH.

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