Glycogen and gluconeogenesis
Introduced| English | Meaning |
|---|---|
| glycogen/ˈɡlaɪkədʒn/ | A highly branched glucose polysaccharide used for energy storage in animals and fungi. |
| glycogen phosphorylase | glycogen phosphorylase |
| glucose-6-phosphatase | glucose-6-phosphatase |
| glucagon/ˈɡluːkæɡən/ | A hormone from pancreatic alpha cells that helps raise blood glucose concentration. |
| insulin/ˈɪnsjuːlɪn/ | A hormone produced by pancreatic beta cells that helps lower blood glucose concentration. |
| gluconeogenesis | Making new glucose from lactate, glycerol or amino acids, mainly in the liver during fasting. |
A brain with no pantry
- The brain burns about 120 g of glucose a day and stores almost none.
- Between meals the body lives on two glucose banks with different owners, and in a longer fast it must make glucose from scratch.
Two banks of glycogen
- Glycogen 糖原 is a branched glucose polymer: α1→4 chains with an α1→6 branch every 8–12 residues.
- The liver stores about 100 g and exports glucose to the blood. Muscle stores about 400 g and keeps it for itself.
Which glycogen store keeps blood glucose up between meals?
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The liver's ~100 g is exported as glucose; muscle's larger ~400 g is used only by the muscle itself.
Taking it apart, building it up
- Glycogen phosphorylase 糖原磷酸化酶 cuts α1→4 bonds using phosphate, not water, so the glucose comes off already phosphorylated and no ATP is spent. Debranching enzyme deals with the α1→6 stubs.
- Glycogen synthase and branching enzyme build it back up when glucose is plentiful.
Match each enzyme to its job.
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Two enzymes take glycogen apart and two build it, and hormones decide which pair is active.
One enzyme decides the owner
- Liver has glucose-6-phosphatase 葡萄糖-6-磷酸酶: glycogen → glucose-1-P → glucose-6-P → free glucose → blood.
- Muscle lacks it, so its glucose-6-P is trapped and burned in place. You cannot export what you cannot dephosphorylate.
Put the route from liver glycogen to blood glucose in order.
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Glucose-6-phosphatase makes the last chemical step, and only the liver (and kidney) has it.
Hormones set the direction
- Glucagon 胰高血糖素 tells the liver to break glycogen down; muscle has no glucagon receptors. Adrenaline acts on both.
- Insulin 胰岛素 tells liver and muscle to store glucose as glycogen.
During a fast, glucagon makes muscle release its glycogen as glucose into the blood.
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Muscle has no glucagon receptors and no glucose-6-phosphatase; its glycogen is only for its own use.
Making new glucose
- Gluconeogenesis 糖异生 runs glycolysis backwards, using different enzymes around the three one-way gates. Its raw materials are lactate (the Cori cycle), amino acids from muscle and glycerol from fat.
- It costs 4 ATP + 2 GTP + 2 NADH per glucose: 6 high-energy phosphates, against glycolysis's net gain of 2.
Gluconeogenesis uses 4 ATP and 2 GTP per glucose. How many high-energy phosphates is that?
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4 + 2 = 6, against glycolysis's net gain of 2. Making glucose costs three times what breaking it down earns.
Worked example: the overnight budget
- Liver glycogen: about 100 g × 4 kcal per g = 400 kcal. The brain needs about 120 g = 480 kcal a day.
- So the liver bank covers well under a day of the brain's needs, and less once other tissues share it. After 12–24 h of fasting, gluconeogenesis must take over.
A liver holds 80 g of glycogen (4 kcal per g). The brain uses 480 kcal a day. If the brain alone used this bank, how many hours would it last?
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80 × 4 = 320 kcal, and 320/480 × 24 h = 16 h. In reality other tissues share it, so gluconeogenesis starts earlier.
Worked example: the bank that cannot be opened
- (Fictional runner) Cramps and dark urine after sprinting. Muscle glycogen phosphorylase is missing (the McArdle pattern): glycogen is stored but cannot be reached.
- ATP falls, myoglobin leaks out, and the lactate rise that hard exercise should cause never comes. No lactate with maximal effort points to a break before glycolysis.
In McArdle disease, why does blood lactate not rise during a sprint?
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Without phosphorylase, stored glycogen cannot feed glycolysis, so pyruvate and lactate stay low; the break is before glycolysis.
Three common slips
- One bank. Muscle glycogen never becomes blood glucose.
- "Gluconeogenesis is free." It costs 6 high-energy phosphates per glucose.
- Glucagon on muscle. Muscle has no glucagon receptors; adrenaline mobilises its glycogen.
Recap
- Liver (~100 g) exports glucose because it has glucose-6-phosphatase; muscle (~400 g) keeps it.
- Phosphorylase and debrancher break glycogen down; synthase and branching enzyme build it.
- Gluconeogenesis costs 4 ATP + 2 GTP + 2 NADH per glucose.