Metabolism is every chemical reaction happening in a cell. It splits into two directions: catabolism breaks complex molecules into simpler ones and harvests energy, and anabolism builds complex molecules from simpler ones using energy.
Glucose-6-phosphateThe first fork. G6P can be stored as glycogen, burned through glycolysis, or diverted to the pentose phosphate pathway for NADPH and ribose-5-P. It cannot leave the cell: only liver and kidney have glucose-6-phosphatase to turn it back into free glucose.
PyruvateThe last cytosolic fork. With oxygen it crosses into the mitochondrion for PDH; without oxygen it becomes lactate; in muscle it is transaminated to alanine; and in the fasting liver it is carboxylated to oxaloacetate to start gluconeogenesis.
Acetyl-CoAThe great convergence: carbohydrate, fat, and ketogenic amino acids all arrive here. It burns in the TCA cycle, leaves as citrate for fatty acid and cholesterol synthesis, or condenses into ketone bodies. It can never become glucose, which is why fat is not a gluconeogenic fuel.
OxaloacetateGatekeeper of the TCA cycle and the doorway out of it. Acetyl-CoA cannot enter the cycle without OAA, so when OAA is drained for gluconeogenesis during fasting, acetyl-CoA backs up and is shunted into ketone bodies. OAA also trades with the urea cycle as aspartate and fumarate.
Read it top to bottom for catabolism, bottom to top for anabolism. Fuels enter at the top, carbon funnels through four junction metabolites, and the electron carriers cash out at the electron transport chain. The four navy pills are the only molecules you need to reason from: know what enters and leaves each one and you can rebuild the rest of the map from memory.
For this chapter and the next two, keep this simple map in your head for catabolism:
NADH and FADH2 → electron transport chain → proton gradient.
Proton gradient → ATP synthase → ATP.
Fatty acids and amino acids plug into the same pipeline at acetyl-CoA (or a TCA intermediate). The TCA cycle’s main job is not ATP - it is making NADH and FADH2 to feed the ETC. Think of the TCA cycle as the electron loader and the ETC as the ATP maker.
From food to fuel: digestion and absorption
Pathway map
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Scroll sideways to see the whole map.
Fuel that reaches the master map Lumen and enterocyte Rate-setting or clinically tested step Intermediate
Only fat skips the liver firstSugars and amino acids go straight into the portal vein, so the liver sees them before anyone else and can buffer the load. Dietary fat leaves in chylomicrons through the lymphatics and enters the bloodstream at the thoracic duct, which means muscle and adipose get first refusal on it. That is why a fatty meal raises plasma triglyceride for hours while a sugary one is cleared much faster.
The two lipases students confusePancreatic lipase works in the gut lumen on food you have just eaten. Lipoprotein lipase sits on the capillary wall of muscle and adipose and unloads triglyceride out of circulating chylomicrons and VLDL. Hormone-sensitive lipase is different again: it is inside the fat cell and releases stored fat during fasting, which is the arrow that feeds β-oxidation.
Lactose intolerance in one lineLactase is a brush border enzyme and the first one to be lost with age. Undigested lactose stays in the lumen, pulls in water osmotically, and is fermented by colonic bacteria into gas and short-chain acids. Nothing is wrong with absorption itself, which is why the symptoms are bloating and diarrhea rather than malnutrition.
Three fuels, three routes, one destination. Carbohydrate and protein are broken to their monomers and go to the liver by the portal vein. Fat is emulsified, cut, ferried in micelles, rebuilt inside the enterocyte, and shipped out in chylomicrons through the lymph. Everything here arrives at the top of the master map as glucose, fatty acids, or amino acids.
Catabolism vs. Anabolism
| Process | Direction | Energy | Examples |
|---------|-----------|--------|----------|
| Catabolism | Large → small | Releases energy (captured as ATP, NADH, FADH2) | Glycolysis, beta-oxidation, amino acid catabolism |
| Anabolism | Small → large | Consumes energy (ATP, NADPH) | Gluconeogenesis, fatty acid synthesis, protein synthesis |
Acetyl-CoA - The Central Hub
All major fuels converge to acetyl-CoA, which enters the TCA cycle:
Some amino acids → directly or via pyruvate → acetyl-CoA.
Energy Carriers
Cells store catabolic energy in three main molecules:
ATP: immediate energy currency. Hydrolysis of ATP to ADP releases ~7.3 kcal/mol.
NADH and FADH2: electron carriers. Deliver electrons to the ETC, which makes ATP.
NADPH: like NADH but used for biosynthetic reductions (fatty acid synthesis, antioxidant regeneration) and made by the pentose phosphate pathway.
What is the difference between catabolism and anabolism?
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Catabolism breaks down complex molecules to simpler ones and releases energy (captured as ATP, NADH, FADH2). Anabolism builds complex molecules from simpler ones and consumes energy (ATP, NADPH). Cells run both simultaneously and regulate the balance based on energy needs and hormonal signals.
How do glucose, fatty acids, and amino acids converge metabolically?
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All three ultimately produce acetyl-CoA, which enters the TCA cycle. Glucose does so via glycolysis → pyruvate → pyruvate dehydrogenase. Fatty acids via beta-oxidation. Amino acids enter at various points depending on their carbon skeleton, but many converge on acetyl-CoA. Acetyl-CoA is the central junction of catabolism.
Why do cells maintain separate NADH and NADPH pools?
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NADH is primarily oxidized back to NAD+ by the electron transport chain to make ATP (catabolism). NADPH is used as a reducing agent in biosynthetic reactions (fatty acid synthesis, cholesterol synthesis) and in antioxidant systems (reducing glutathione). Keeping them separate lets the cell independently control catabolic energy production and anabolic/reductive reactions.
