Glycerol metabolism in the liver
In the liver, glycerol kinase (an enzyme that adds a phosphate group) acts first, then the product is oxidised (it loses hydrogen) to dihydroxyacetone phosphate (DHAP), which joins glycolysis.
Remember
In the liver, glycerol kinase adds a phosphate group to glycerol first, and only then does glycerol-3-phosphate dehydrogenase oxidise that glycerol-3-phosphate to DHAP, the point at which glycerol joins glycolysis.
Memory aid
tag, then take hydrogen
Glycerol is tagged with a phosphate by a kinase, then loses hydrogen to a dehydrogenase, arriving at DHAP.
Stored fat is held as triacylglycerol (three fatty acids attached to one glycerol). In fasting, glucagon activates hormone-sensitive lipase, the fat-cell enzyme that splits triacylglycerol into fatty acids and glycerol. Fat cells cannot reuse glycerol well, so it travels in the blood to the liver, where hepatocytes have plenty of glycerol kinase.
Two steps then let glycerol join the carbohydrate pathways. First, glycerol kinase uses ATP to add a phosphate group to glycerol, which makes glycerol-3-phosphate. A kinase is simply an enzyme that adds a phosphate group. This step also traps glycerol inside the cell, because molecules given a phosphate group cannot easily cross the cell membrane.
Next, glycerol-3-phosphate dehydrogenase (an enzyme that removes hydrogen atoms, here passing them on to make NADH) oxidises glycerol-3-phosphate to dihydroxyacetone phosphate (DHAP). The dehydrogenase cannot act until glycerol has been given its phosphate group.
DHAP is a three-carbon intermediate of glycolysis (the pathway that breaks glucose down to pyruvate), meaning one of the molecules the pathway passes through, so glycerol joins glycolysis in the middle, after the early six-carbon steps. The NADH formed in the second step can feed the electron transport chain to generate ATP. DHAP can also be used to make glucose by gluconeogenesis, which helps to maintain blood glucose in prolonged fasting. The fatty acids from the same triacylglycerol follow a different route.
Key facts
- Release of glycerol
- in fasting, glucagon activates hormone-sensitive lipase, which frees glycerol from triacylglycerol.
- Step one
- glycerol kinase uses ATP to add a phosphate group to glycerol, giving glycerol-3-phosphate.
- Step two
- glycerol-3-phosphate dehydrogenase oxidises glycerol-3-phosphate to dihydroxyacetone phosphate, and NADH is produced.
- Entry point
- glycerol joins glycolysis as DHAP, after the early six-carbon steps.
- Fate of DHAP
- it can go on through glycolysis for energy or be used to make glucose by gluconeogenesis.
- Missing glycerol kinase
- a rare inherited lack of the enzyme shows why the first step matters, because glycerol builds up in the blood.
Exam traps
- Hexokinase, the kinase that adds a phosphate group to glucose, does not act on glycerol, because glycerol needs its own kinase.
- Glycerol-3-phosphate dehydrogenase is not the first enzyme to act on glycerol, because it works second and cannot work until glycerol kinase has made its substrate.
- Hormone-sensitive lipase, which works in fat cells to release glycerol and fatty acids from stored triglyceride, supplies glycerol and does not metabolise it in the liver.
Read the full notes
Tested in 6 SimpleMed+ questions
Practice it in Metabolism, with the answer and a full explanation after every question.
Practice these questions