Biochemistry

Metabolic pathways as maps you can tap, every enzyme in 3D with its active site, reactions atom by atom, and the disease when a step fails. Open data (PDB, PubChem, Reactome), in our own words.

31 pathways · 104 molecules · 131 enzymes and proteins

Metabolic pathways

Build a molecule

Join amino acids into a peptide and fold it into an α-helix, or build a DNA strand with its complement.

Molecules

• Ammonia (ammonium)Ammonia comes from breaking down amino acids. It is toxic to the brain, so the liver turns it into urea.
• UreaUrea is how the body gets rid of spare nitrogen: the liver makes it and the kidney excretes it.
• Glutamate (glutamic acid)Glutamate gathers the nitrogen of amino acids and hands it on for urea; in the brain it is the main excitatory neurotransmitter.
• GlutamineGlutamine is the most abundant amino acid in blood: it carries ammonia safely and feeds the gut, the kidney and immune cells.
• AlanineAlanine carries nitrogen from muscle to the liver, where it becomes pyruvate again to make glucose (glucose–alanine cycle).
• PhenylalaninePhenylalanine is an essential aromatic amino acid. The liver turns it into tyrosine; if it cannot, it builds up and damages the brain.
• TyrosineTyrosine comes from phenylalanine and is the starting point of dopamine, adrenaline, melanin and thyroid hormones.
• TryptophanTryptophan is an essential amino acid that gives serotonin, melatonin and part of our niacin (vitamin B3).
• HomocysteineHomocysteine forms when methionine donates methyl groups. If it builds up, it damages vessels and favours thrombosis.
• S-adenosylmethionine (SAM)SAM is the body's main methyl-group donor: it methylates DNA, neurotransmitters, phospholipids and creatine.
• Tetrahydrobiopterin (BH4)BH4 is the cofactor of the phenylalanine, tyrosine and tryptophan hydroxylases and of nitric oxide synthase.
• GlucoseGlucose is the sugar carried in the blood and the main fuel of the brain and the red blood cells.
• Glucose 6-phosphateGlucose 6-phosphate is glucose trapped in the cell: from here it can go to energy, to glycogen or to the pentose pathway.
• Fructose 1,6-bisphosphateFructose 1,6-bisphosphate is the two-phosphate sugar made by the committed step of glycolysis; aldolase splits it in two.
• PyruvatePyruvate is where glycolysis ends: with oxygen it enters the mitochondria and is burned; without oxygen it becomes lactate.
• LactateLactate is made when cells work without enough oxygen; the liver turns it back into glucose. Measuring it helps spot shock.
• ATP (adenosine triphosphate)ATP is the cell's energy currency: giving up its last phosphate pays for movement, transport and building.
• NAD⁺ (nicotinamide adenine dinucleotide)NAD⁺ picks up electrons in glycolysis and the Krebs cycle and carries them to the mitochondria as NADH. It is made from niacin.
• Acetyl-CoAAcetyl-CoA is where sugars, fats and proteins meet: it enters the Krebs cycle or is used to make fat, cholesterol and ketone bodies.
• CitrateCitrate is the first molecule of the Krebs cycle; it also carries acetyl to the cytosol to make fat and slows glycolysis when energy is plentiful.
• GlycogenGlycogen is the body's glucose store: a highly branched polymer kept in liver and muscle.
• NADPHNADPH is the electron currency for building molecules and fighting oxidative damage; it comes mainly from the pentose pathway.
• Ribose 5-phosphateRibose 5-phosphate is the five-carbon sugar the cell uses to build DNA, RNA, ATP, NAD and coenzyme A.
• UDP-glucoseUDP-glucose is activated glucose: the form enzymes use to build glycogen and to swap sugars with galactose.
• FructoseFructose is the sugar of fruit and honey, and half of table sugar; the liver handles almost all of it.
• GalactoseGalactose is half of lactose, the sugar of milk; the liver turns it into glucose through the Leloir pathway.
• CeramideCeramide is the core of every sphingolipid: sphingosine joined to a fatty acid. It also acts as a stress and cell-death signal.
• SphingomyelinSphingomyelin is the sphingolipid with phosphate: rich in myelin and the outer leaflet of membranes. It builds up in Niemann–Pick disease.
• Phosphatidylcholine (lecithin)Phosphatidylcholine, or lecithin, is the most abundant membrane phospholipid and the basis of the surfactant that keeps alveoli open.
• Glucosylceramide (glucocerebroside)Glucosylceramide is a ceramide carrying one glucose. It is the lipid that builds up in macrophages in Gaucher disease.
• Galactosylceramide (galactocerebroside)Galactosylceramide is a ceramide with one galactose and a main myelin lipid. Failure to break it down causes Krabbe disease.
• SulfatideSulfatide is a galactosylceramide with a sulfate group. It is part of myelin and builds up in metachromatic leukodystrophy.
• GM2 gangliosideGM2 ganglioside is a sialic acid-containing glycolipid of neuronal membranes. It builds up in neurons in Tay–Sachs disease.
• Hyaluronic acid (hyaluronan)Hyaluronic acid is a giant, sulfate-free glycosaminoglycan that holds water: it lubricates joints and gives bulk to the vitreous and skin.
• CholesterolCholesterol is a 27-carbon sterol that stiffens membranes and is the raw material for steroid hormones, bile acids and vitamin D.
• MevalonateMevalonate is the product of HMG-CoA reductase: a six-carbon compound that commits carbon to cholesterol and isoprenoids.
• Isopentenyl pyrophosphate (IPP)Isopentenyl pyrophosphate is the five-carbon building block (active isoprene) used to build cholesterol and many other isoprenoids.
• SqualeneSqualene is a linear 30-carbon hydrocarbon, with no oxygen, that folds up to form the first sterol.
• LanosterolLanosterol is the first sterol of the pathway: it already has the four rings but carries three extra methyl groups.
• Cholic acidCholic acid is one of the two primary bile acids: the liver makes it from cholesterol to emulsify fats in the gut.
• Palmitate (palmitic acid)Palmitate is the 16-carbon saturated fatty acid the body makes and the most common one in human fat.
• Malonyl-CoAMalonyl-CoA is both the building block of fat synthesis and the signal that stops fat being burned at the same time.
• Carnitine (L-carnitine)Carnitine is the carrier that takes long-chain fatty acids into the mitochondrion to be burned.
• Acetoacetate (acetoacetic acid)Acetoacetate is the first ketone body the liver makes; other tissues turn it back into acetyl-CoA.
• β-Hydroxybutyrateβ-Hydroxybutyrate is the most abundant ketone body in blood; it is measured to diagnose and follow ketoacidosis.
• Propionyl-CoAPropionyl-CoA is the 3-carbon remnant left by odd-chain fatty acids and some amino acids; it ends up as succinyl-CoA.
• CreatineCreatine is a small nitrogen compound that muscle and brain use as a quick energy reserve, stored as phosphocreatine.
• CreatinineCreatinine is the waste product of muscle creatine. It is made at a steady rate and cleared by the kidneys, so it is the main blood marker of filtration.
• Nitric oxide (NO)Nitric oxide is a short-lived gas made in the body that widens blood vessels, acts as a nerve messenger and is used by immune cells to kill microbes.
• Globotriaosylceramide (Gb3)Gb3 is a ceramide carrying three sugars. α-Galactosidase A breaks it down; in Fabry disease it builds up in vessels, kidney, heart and nerves.
• HemeHeme is a porphyrin ring with an iron at its centre; it lets hemoglobin carry oxygen and cytochromes move electrons.
• BilirubinBilirubin is the yellow pigment left when heme is broken down; when it builds up, it turns skin and eyes yellow (jaundice).
• Protoporphyrin IXProtoporphyrin IX is the heme ring before it receives iron; it is red, fluorescent and builds up in protoporphyria.
• PorphobilinogenPorphobilinogen is the first pyrrole ring of heme synthesis; high in urine, it points to an acute porphyria attack.
• δ-Aminolevulinic acid (ALA)ALA is the first committed molecule of heme synthesis; it rises in acute porphyrias and lead poisoning.
• Cyclic AMP (cAMP)The classic second messenger: adenylyl cyclase makes it from ATP when a hormone arrives, and phosphodiesterase destroys it.
• CortisolThe main glucocorticoid: it raises glucose, mobilises reserves in fasting and stress, and damps down inflammation.
• AldosteroneThe zona glomerulosa mineralocorticoid: it makes the kidney keep sodium and water and excrete potassium and hydrogen ions.
• 17-Hydroxyprogesterone (17-OHP)An intermediate of cortisol synthesis; it piles up when 21-hydroxylase is missing, which is why newborn screening measures it.
• Thyroxine (T4)The hormone the thyroid makes most; it is mainly a prohormone that tissues turn into active T3.
• Triiodothyronine (T3)The active form of thyroid hormone: it binds nuclear receptors and speeds up metabolism, the heart and brain development.
• AdrenalineThe adrenal medulla hormone for acute stress: it raises glucose and fatty acids and speeds up the heart.
• 5-Methylcytosine5-Methylcytosine is cytosine with an extra methyl group; it is the main epigenetic mark on DNA and usually switches genes off.
• α-Amanitinα-Amanitin is the toxin of mushrooms such as Amanita phalloides; it blocks RNA polymerase II and destroys liver cells.
• PRPP (phosphoribosyl pyrophosphate)PRPP is activated ribose: the starting point for making and recycling every nucleotide.
• IMP (inosine monophosphate)IMP is the first complete purine the cell makes; AMP and GMP come from it.
• Uric acidUric acid is the final product of purines in humans; when it builds up, it forms crystals that cause gout and stones.
• HypoxanthineHypoxanthine is a purine the cell can either recycle (HGPRT) or break down to uric acid (xanthine oxidase).
• Orotic acidOrotic acid is the newly made pyrimidine ring before it joins the sugar; in urine it signals a block in the pathway or the urea cycle.
• dTMP (thymidine monophosphate)dTMP is the thymine nucleotide, unique to DNA; many cancer drugs work by preventing its formation.
• Ubiquinone (coenzyme Q₁₀)Ubiquinone is a fatty molecule that moves within the mitochondrial membrane and carries electrons from complexes I and II to complex III.
• Glutathione (GSH)Glutathione is a tripeptide with a thiol group that neutralises oxidants and toxins; it is the main antioxidant inside the cell.
• FAD (flavin adenine dinucleotide)FAD is the riboflavin-derived coenzyme that collects electrons in the Krebs cycle and β-oxidation and hands them to ubiquinone.
• Arachidonic acidArachidonic acid is a 20-carbon omega-6 fatty acid stored in cell membranes. Released on demand, it is the source of all eicosanoids.
• DopamineDopamine is a catecholamine neurotransmitter for movement, reward and prolactin control, and the precursor of norepinephrine.
• L-DOPA (levodopa)L-DOPA is the first product of catecholamine synthesis. Given as levodopa, it crosses into the brain and replaces dopamine in Parkinson disease.
• LeucineLeucine is an essential branched-chain amino acid. It is purely ketogenic and a strong signal for muscle protein synthesis.
• MelatoninMelatonin is the pineal hormone of darkness. It rises at night and tells the body's clock that it is time to sleep.
• MethionineMethionine is an essential sulfur amino acid. It starts every protein and is the source of SAM, the body's main methyl donor.
• Norepinephrine (noradrenaline)Norepinephrine is the transmitter of sympathetic nerves and a hormone of the adrenal medulla. It raises blood pressure and alertness.
• Prostaglandin H₂ (PGH₂)PGH₂ is the unstable product of COX. Each cell type turns it into its own prostanoid: TXA₂, PGI₂, PGE₂, PGD₂ or PGF₂α.
• S-Adenosylhomocysteine (SAH)SAH is what is left of SAM after it gives away its methyl group. It must be cleared quickly because it blocks methylation.
• Serotonin (5-hydroxytryptamine)Serotonin is made from tryptophan. It is a brain neurotransmitter for mood and sleep, and in the gut it controls motility.
• SphingosineSphingosine is the amino alcohol backbone of all sphingolipids. It is released when lysosomes break down ceramide.
• Thromboxane A₂ (TXA₂)TXA₂ is the platelet signal that calls more platelets and narrows vessels. Aspirin blocks its synthesis for the platelet's whole life.
• HistidineHistidine is an essential amino acid with an imidazole ring that gains or loses protons at physiological pH: it buffers and takes part in catalysis.
• HydroxyprolineHydroxyproline is a proline with an added OH group inside collagen; without vitamin C it is not formed and collagen falls apart.
• EthanolThe alcohol in drinks: a small molecule that crosses every membrane and that the liver oxidises to acetaldehyde and acetate.
• AcetaldehydeThe first product of alcohol in the liver: highly reactive, it causes hangover symptoms, flushing and part of the liver damage and cancer.
• NAPQI (N-acetyl-p-benzoquinone imine)The toxic metabolite of acetaminophen: glutathione neutralises it, but when glutathione runs out it destroys liver cells.
• N-acetylcysteine (NAC)A cysteine derivative that refills liver glutathione; it is the antidote for acetaminophen poisoning.
• Fomepizole (4-methylpyrazole)An alcohol dehydrogenase inhibitor: it stops methanol and ethylene glycol from being turned into their toxic acids.
• Vitamin A (retinol)Vitamin A lets you see in dim light, keeps the linings of the eye, skin and gut healthy, and supports immunity.
• Vitamin D (calcitriol)Vitamin D is made in sunlit skin and activated in the liver and kidney; it raises calcium and phosphate to mineralise bone.
• Vitamin E (α-tocopherol)Vitamin E is the membrane antioxidant: it slows the oxidation of cell fats, especially in nerves and red blood cells.
• Vitamin K (phylloquinone)Vitamin K lets the liver activate clotting factors; without it blood takes too long to clot.
• Thiamine (vitamin B1)Thiamine, as thiamine pyrophosphate, is essential for drawing energy from glucose, especially in the brain and heart.
• Riboflavin (vitamin B2)Riboflavin forms FAD and FMN, the electron carriers of many oxidation reactions in the cell.
• Niacin (vitamin B3)Niacin forms NAD⁺ and NADP⁺, the coenzymes that move electrons in hundreds of reactions; its lack causes pellagra.
• Pantothenic acid (vitamin B5)Pantothenic acid forms coenzyme A, which carries acyl groups such as acetyl in fat, sugar and protein metabolism.
• Vitamin B6 (pyridoxal phosphate)Vitamin B6, as pyridoxal phosphate, is the coenzyme of amino acid metabolism: transamination, neurotransmitters and heme.
• Biotin (vitamin B7)Biotin is the coenzyme of the carboxylases, the enzymes that add CO₂ in gluconeogenesis and fatty acid synthesis.
• Folate (vitamin B9)Folate carries one-carbon groups to build DNA; its lack causes megaloblastic anaemia and neural tube defects.
• Vitamin C (ascorbic acid)Vitamin C is needed to make stable collagen, absorb iron and protect against oxidative damage; its lack causes scurvy.

Enzymes and proteins

• Carbamoyl phosphate synthetase I (CPS-I)CPS-I opens the urea cycle in liver mitochondria: it joins ammonia and CO₂ using 2 ATP to make carbamoyl phosphate.
• Ornithine transcarbamylase (OTC)OTC joins carbamoyl phosphate to ornithine to make citrulline. Its X-linked deficiency is the most common urea cycle disorder.
• Argininosuccinate synthetase (ASS)Argininosuccinate synthetase joins citrulline and aspartate in the cytosol; this is how the second nitrogen of urea enters.
• Argininosuccinate lyase (ASL)Argininosuccinate lyase splits argininosuccinate into arginine and fumarate; the fumarate links the urea cycle to the Krebs cycle.
• Arginase 1Arginase 1 closes the urea cycle in the liver cytosol: it releases urea and regenerates ornithine.
• Alanine aminotransferase (ALT, GPT)ALT moves the amino group of alanine to α-ketoglutarate. Measured in blood, it is the most used marker of liver damage.
• Aspartate aminotransferase (AST, GOT)AST swaps aspartate and oxaloacetate with glutamate and α-ketoglutarate. It supplies urea cycle aspartate and marks liver injury.
• Glutamate dehydrogenase (GDH)Glutamate dehydrogenase frees ammonia from glutamate in liver mitochondria and links amino acid breakdown to the Krebs cycle.
• Glutamine synthetaseGlutamine synthetase traps free ammonia by joining it to glutamate. This protects the brain and carries nitrogen safely in the blood.
• Phenylalanine hydroxylase (PAH)Phenylalanine hydroxylase turns phenylalanine into tyrosine in the liver. If it fails, phenylalanine builds up: phenylketonuria.
• Branched-chain α-keto acid dehydrogenase (BCKDH)BCKDH breaks down leucine, isoleucine and valine after their transamination. If it fails, urine smells like maple syrup.
• Cystathionine β-synthase (CBS)Cystathionine β-synthase joins homocysteine and serine on the route to cysteine. Its deficiency causes classic homocystinuria.
• Methionine synthaseMethionine synthase moves a methyl from 5-methyltetrahydrofolate to homocysteine. It links the folate cycle with vitamin B12.
• Tyrosine hydroxylaseTyrosine hydroxylase makes L-DOPA from tyrosine: the rate-limiting step for making dopamine, noradrenaline and adrenaline.
• HexokinaseHexokinase opens glycolysis: it puts a phosphate on glucose and traps it inside the cell.
• Phosphofructokinase-1 (PFK-1)Phosphofructokinase-1 is the main switch of glycolysis: it decides whether glucose is burned according to the cell's energy.
• Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)GAPDH is the glycolysis enzyme that makes NADH and builds a high-energy bond; arsenic fools it.
• Pyruvate kinasePyruvate kinase makes the last step of glycolysis and its second ATP; if it fails in red cells, they are destroyed too early.
• Hemoglobin and 2,3-BPGHemoglobin carries oxygen in the blood; 2,3-BPG, made by a side branch of red-cell glycolysis, helps it let go in the tissues.
• Pyruvate dehydrogenase complex (PDH)Pyruvate dehydrogenase is the gate between glycolysis and the Krebs cycle; it needs five coenzymes and four B vitamins.
• Citrate synthaseCitrate synthase opens each turn of the Krebs cycle: it joins acetyl-CoA to oxaloacetate to make citrate.
• Isocitrate dehydrogenaseIsocitrate dehydrogenase sets the pace of the Krebs cycle; its mutated relatives in some cancers make an oncometabolite.
• α-Ketoglutarate dehydrogenaseα-Ketoglutarate dehydrogenase is PDH's twin inside the cycle: it releases the second CO₂ and uses the same vitamins.
• Succinate dehydrogenase (complex II)Succinate dehydrogenase is the Krebs cycle enzyme that is also part of the respiratory chain; if it fails, stored succinate favours tumours.
• Pyruvate carboxylasePyruvate carboxylase turns pyruvate into oxaloacetate inside the mitochondrion: the first step in making glucose and in topping up the Krebs cycle.
• Phosphoenolpyruvate carboxykinase (PEPCK)PEPCK turns oxaloacetate into phosphoenolpyruvate using GTP; it is a key gluconeogenic enzyme switched on by glucagon and off by insulin.
• Fructose-1,6-bisphosphatase (FBPase-1)Fructose-1,6-bisphosphatase removes a phosphate from fructose 1,6-bisphosphate and is the main control point of gluconeogenesis.
• Glucose-6-phosphataseGlucose-6-phosphatase releases glucose into the blood from liver and kidney; it is the last step of both gluconeogenesis and glycogenolysis.
• Glycogen synthaseGlycogen synthase lengthens glycogen chains with glucose taken from UDP-glucose; insulin activates it after a meal.
• Glycogen phosphorylaseGlycogen phosphorylase releases glucose 1-phosphate from glycogen; it controls glycogen breakdown in liver and muscle.
• Glycogen debranching enzymeThe debranching enzyme removes glycogen's branches so phosphorylase can keep going; it has two activities in a single protein.
• Glucose-6-phosphate dehydrogenase (G6PD)G6PD makes NADPH in the pentose pathway; in the red blood cell it is the only defence against oxidative damage.
• TransketolaseTransketolase swaps two-carbon units between sugars in the pentose pathway; it needs thiamine (vitamin B1).
• Aldolase BLiver aldolase B splits fructose 1-phosphate into two trioses; if it is missing, dietary fructose becomes toxic.
• Galactose-1-phosphate uridylyltransferase (GALT)GALT is the central enzyme of the Leloir pathway: it turns galactose 1-phosphate into a sugar the body can use. Its absence causes classic galactosaemia.
• Glucocerebrosidase (acid β-glucosidase)Glucocerebrosidase is the lysosomal enzyme that removes glucose from glucosylceramide. Its absence causes Gaucher disease.
• Hexosaminidase A (β-hexosaminidase A)Hexosaminidase A is the lysosomal enzyme that cleaves GM2 ganglioside. Without its α subunit, neurons fill with GM2: Tay–Sachs disease.
• α-Galactosidase Aα-Galactosidase A removes the terminal galactose from globotriaosylceramide in the lysosome. Its X-linked loss causes Fabry disease.
• Acid sphingomyelinaseAcid sphingomyelinase splits sphingomyelin into ceramide and phosphocholine inside the lysosome. Its absence causes Niemann–Pick types A and B.
• α-L-Iduronidaseα-L-Iduronidase removes iduronic acid from the end of dermatan and heparan sulfate in the lysosome. Its absence causes mucopolysaccharidosis I (Hurler).
• LDL receptorThe LDL receptor pulls LDL particles out of the blood into the cell; when it fails, LDL cholesterol is high from birth.
• Lipoprotein lipase (LPL)Lipoprotein lipase, anchored in capillaries, cuts the triglycerides of chylomicrons and VLDL so muscle and fat can take up the fatty acids.
• LCAT (lecithin–cholesterol acyltransferase)LCAT esterifies free cholesterol on HDL; the ester sinks into the particle core, which matures from a disc into a sphere.
• CETP (cholesteryl ester transfer protein)CETP moves cholesteryl esters from HDL to ApoB lipoproteins and brings triglycerides back.
• PCSK9PCSK9 binds the LDL receptor and sends it to be destroyed; blocking it leaves more receptors and lowers LDL cholesterol sharply.
• Squalene epoxidaseSqualene epoxidase activates squalene with oxygen so it can close into rings; it is the second control point of cholesterol synthesis.
• Cholesterol 7α-hydroxylase (CYP7A1)Liver CYP7A1 takes the first step in turning cholesterol into bile acids and sets the pace of that pathway.
• Apolipoprotein B (ApoB-100 and ApoB-48)ApoB is the structural protein of chylomicrons, VLDL, IDL and LDL: each of these particles carries a single copy.
• Apolipoprotein E (ApoE)ApoE is the key that lets chylomicron remnants and IDL into the liver; its variants change cholesterol and Alzheimer risk.
• Acetyl-CoA carboxylase (ACC)Acetyl-CoA carboxylase decides whether the body makes fat: it turns acetyl-CoA into malonyl-CoA using biotin and ATP.
• Fatty acid synthase (FAS)Fatty acid synthase is one giant protein with seven activities that builds palmitate two carbons at a time.
• Carnitine palmitoyltransferase I (CPT-I)CPT-I is the gate for fat into the mitochondrion: it moves the fatty acid from CoA to carnitine so it can cross.
• Medium-chain acyl-CoA dehydrogenase (MCAD)MCAD carries out the first β-oxidation step for fatty acids of 6 to 12 carbons; its lack is the most common defect in the group.
• Mitochondrial HMG-CoA synthase (HMGCS2)Mitochondrial HMG-CoA synthase is the enzyme that switches on ketone body production in the liver during fasting.
• β-Hydroxybutyrate dehydrogenase (BDH1)This enzyme turns acetoacetate into β-hydroxybutyrate in the liver, and back again in tissues that burn ketones.
• Succinyl-CoA:3-ketoacid CoA transferase (SCOT)SCOT lets muscle, heart and brain use ketones: it moves CoA from succinyl-CoA onto acetoacetate.
• Hormone-sensitive lipase (HSL)Hormone-sensitive lipase releases fatty acids from stored fat when the body needs energy (fasting, stress, exercise).
• Proteasome (26S, β5 subunit)The proteasome is the cell's shredder for proteins tagged with ubiquitin. Myeloma drugs such as bortezomib block its cutting site.
• Nitric oxide synthase (NOS)Nitric oxide synthase turns arginine into citrulline and nitric oxide, a gas that relaxes blood vessels, carries nerve signals and helps kill microbes.
• Iduronate 2-sulfatase (I2S)Iduronate 2-sulfatase strips the sulfate off iduronic acid in dermatan and heparan sulfate. Its loss causes Hunter syndrome (MPS II).
• Arylsulfatase A (ARSA)Arylsulfatase A removes the sulfate from sulfatide in the lysosome, helped by saposin B. Without it sulfatide destroys myelin: metachromatic leukodystrophy.
• Galactocerebrosidase (GALC)Galactocerebrosidase breaks down galactosylceramide and the toxic psychosine in lysosomes. Its deficiency kills myelin-forming cells: Krabbe disease.
• Hexosaminidase B (β-hexosaminidase B)Hexosaminidase B is the ββ form of β-hexosaminidase. It trims amino sugars from glycolipids and oligosaccharides; losing the β subunit causes Sandhoff disease.
• ALA synthaseALA synthase opens and controls heme synthesis: it joins glycine and succinyl-CoA in the mitochondrion.
• ALA dehydrataseALA dehydratase joins two ALA into the first pyrrole ring; it is the enzyme most sensitive to lead.
• Porphobilinogen deaminasePorphobilinogen deaminase strings four pyrroles together; its deficiency causes acute intermittent porphyria.
• Uroporphyrinogen decarboxylaseUroporphyrinogen decarboxylase removes four carboxyls from the ring; when it fails in the liver, porphyria cutanea tarda appears.
• FerrochelataseFerrochelatase puts iron inside protoporphyrin and finishes heme synthesis in the mitochondrion.
• Heme oxygenaseHeme oxygenase breaks the heme ring, releasing biliverdin, iron and carbon monoxide.
• Biliverdin reductaseBiliverdin reductase turns green biliverdin into yellow bilirubin using NADPH.
• UGT1A1 (bilirubin UDP-glucuronosyltransferase)Liver UGT1A1 attaches glucuronic acid to bilirubin so it dissolves in bile; its failure causes Gilbert and Crigler-Najjar.
• MyoglobinMyoglobin stores oxygen inside muscle; it has a single heme and gives it up only when oxygen falls very low.
• Adenylyl cyclaseThe enzyme that turns ATP into cAMP when a hormone activates a Gs-coupled receptor; it is the signal's amplifier.
• Protein kinase A (PKA)The kinase that turns cAMP into action: it phosphorylates glycogen, fat and glucose enzymes during fasting and stress.
• AMP-activated protein kinase (AMPK)The cell's fuel gauge: when ATP falls and AMP rises, it switches off what spends energy and switches on what makes it.
• mTOR (mechanistic target of rapamycin)A kinase that decides whether the cell grows: with enough nutrients, insulin and energy it switches on protein synthesis and stops autophagy.
• Insulin receptorA receptor tyrosine kinase: insulin switches it on and it phosphorylates the proteins that move GLUT4 to the membrane and store glucose.
• Aromatase (CYP19A1)The enzyme that turns androgens into oestrogens; it is in the ovary, placenta, fat, bone and brain.
• 21-Hydroxylase (CYP21A2)An adrenal enzyme needed to make cortisol and aldosterone; its deficiency causes 95 % of congenital adrenal hyperplasia.
• 11β-Hydroxylase (CYP11B1)It makes the last step of cortisol in fasciculata mitochondria; its deficiency causes adrenal hyperplasia with hypertension.
• 17α-Hydroxylase/17,20-lyase (CYP17A1)One enzyme with two activities that decide whether pregnenolone goes to cortisol, to androgens or only to aldosterone.
• Thyroid peroxidase (TPO)The thyroid's key enzyme: it oxidises iodide, attaches it to thyroglobulin and joins iodinated tyrosines to form T4 and T3.
• Iodothyronine deiodinases (DIO1, DIO2, DIO3)Three selenoenzymes that activate T4 to T3 or inactivate it; they decide how much active thyroid hormone each tissue gets.
• DNA polymerasesDNA polymerases copy DNA by adding nucleotides one by one to the 3' end of the new strand, following the template strand.
• DNA helicasesHelicases are motors that separate the two DNA strands using ATP; they open the replication fork and help repair DNA.
• Topoisomerases (I and II)Topoisomerases cut and rejoin DNA to remove the twists that build up when it opens; they are the target of several anticancer drugs.
• Bacterial DNA gyrase (target of fluoroquinolones)DNA gyrase is a bacteria-only topoisomerase II that introduces negative supercoils; fluoroquinolones block it.
• TelomeraseTelomerase lengthens chromosome ends (telomeres) using its own RNA as a template; it is active in stem cells and in most cancers.
• RNA polymerases I, II and IIIRNA polymerases copy DNA into RNA; human cells have three in the nucleus, each dedicated to a type of RNA.
• SpliceosomeThe spliceosome is a large RNA–protein machine that cuts introns out of pre-mRNA and joins the exons; its catalytic core is RNA.
• Ribosome (and the antibiotics that target it)The ribosome is the protein factory: it reads mRNA and joins amino acids. Bacterial ribosomes differ from human ones, so many antibiotics target them.
• PRPP synthetaseMakes PRPP, the activated ribose needed to build and recycle every nucleotide.
• Glutamine-PRPP amidotransferaseThe main switch of purine synthesis: the committed step that turns off when there are enough nucleotides.
• Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)Recycles the bases hypoxanthine and guanine so they need not be built again; its loss causes Lesch-Nyhan syndrome.
• Adenine phosphoribosyltransferase (APRT)Recycles free adenine; when it is missing, adenine turns into an insoluble compound that forms kidney stones.
• Xanthine oxidasePerforms the last two steps of purine breakdown and makes uric acid; it is the target of allopurinol and febuxostat.
• Adenosine deaminase (ADA)Clears adenosine and deoxyadenosine; without it lymphocytes die and a severe combined immunodeficiency appears.
• Ribonucleotide reductaseTurns ribonucleotides into deoxyribonucleotides, the building blocks of DNA; it is the target of hydroxyurea.
• CAD (carbamoyl phosphate synthetase II)A single protein performs the first three steps of pyrimidine synthesis; its CPS-II part is the pathway's control point.
• Dihydroorotate dehydrogenase (DHODH)The only mitochondrial enzyme of pyrimidine synthesis; leflunomide, used in rheumatoid arthritis, blocks it.
• UMP synthaseFinishes the first pyrimidine: joins orotate to ribose phosphate and turns it into UMP. Its loss causes orotic aciduria.
• IMP dehydrogenase (IMPDH)Opens the route from IMP to GMP; lymphocytes rely on it heavily, so mycophenolate blocks it to prevent rejection.
• Complex I (NADH dehydrogenase)Complex I is NADH's entry door to the respiratory chain: it passes NADH's electrons to ubiquinone and pumps protons.
• Complex III (cytochrome bc₁)Complex III passes electrons from ubiquinol to cytochrome c and, through the Q cycle, pumps protons.
• Cytochrome c oxidase (complex IV)Cytochrome c oxidase is the last complex of the chain: it hands the electrons to oxygen, makes water and pumps protons.
• ATP synthase (complex V)ATP synthase is a molecular motor: protons flowing back into the matrix spin it, and each turn makes ATP from ADP and phosphate.
• UCP1 (thermogenin)UCP1 is a proton channel in brown fat: it lets the gradient discharge without making ATP, so the energy leaves as heat.
• Superoxide dismutase (SOD)Superoxide dismutase turns the superoxide radical into hydrogen peroxide and oxygen; it is the first antioxidant line.
• CatalaseCatalase breaks hydrogen peroxide down into water and oxygen; it works mainly in peroxisomes and in red blood cells.
• Glutathione peroxidase (GPX)Glutathione peroxidase removes hydrogen peroxide and lipid peroxides using glutathione; it contains selenium.
• Cytochrome cCytochrome c is a small heme protein that carries one electron at a time from complex III to complex IV; out of place, it triggers apoptosis.
• CollagenCollagen is the body's most abundant protein: three braided chains that give strength to bone, skin, tendons and vessels.
• ElastinElastin lets arteries, lungs and skin stretch and spring back; it is built on a scaffold of fibrillin.
• Fibrillin-1Fibrillin-1 forms microfibrils that support elastic fibres and store TGF-β; its variants cause Marfan syndrome.
• AlbuminAlbumin is the most abundant plasma protein: it keeps water inside vessels and carries fatty acids, bilirubin, calcium and drugs.
• Immunoglobulins (antibodies)Immunoglobulins are antibodies: Y-shaped proteins made by plasma cells to recognise and tag anything foreign.
• α1-antitrypsinα1-antitrypsin, made in the liver, restrains neutrophil elastase and protects the lung; when it misfolds, it damages the liver too.
• Transthyretin (prealbumin)Transthyretin carries thyroxine and vitamin A in blood; if its tetramer falls apart, it forms amyloid in the heart and nerves.
• Prion protein (PrP)The normal prion protein sits on neurons; its misfolded form turns the others into copies of itself and destroys the brain.
• HMG-CoA reductaseHMG-CoA reductase makes mevalonate, the slow step that sets how much cholesterol the cell builds. Statins block it.
• Cyclooxygenase (COX-1 and COX-2)Cyclooxygenase turns arachidonic acid into the parent of all prostaglandins and thromboxanes. Aspirin and NSAIDs block it.
• Angiotensin-converting enzyme (ACE)ACE makes angiotensin II, which narrows vessels, and breaks down bradykinin, which widens them. ACE inhibitors block it.
• Vitamin K epoxide reductase (VKORC1)VKORC1 recycles used vitamin K so the liver can keep activating clotting factors. Warfarin blocks it.
• Dihydrofolate reductase (DHFR)DHFR turns dihydrofolate back into tetrahydrofolate, the carrier of one-carbon units for DNA building blocks. Methotrexate blocks it.
• Thymidylate synthaseThymidylate synthase makes dTMP, the thymine building block that only DNA needs. Fluorouracil blocks it.
• Na⁺/K⁺-ATPase (sodium pump)The sodium pump spends ATP to push Na⁺ out of the cell and bring K⁺ in. Digoxin blocks it in the heart.
• H⁺/K⁺-ATPase (gastric proton pump)The gastric proton pump spends ATP to swap H⁺ for K⁺ and makes stomach acid. Proton pump inhibitors block it.
• Alcohol dehydrogenase (ADH)A liver enzyme that starts alcohol removal: it turns it into acetaldehyde using NAD⁺ and a zinc atom.
• Aldehyde dehydrogenase 2 (ALDH2)A mitochondrial enzyme that clears the acetaldehyde made from alcohol; when it fails, drinking causes flushing, nausea and palpitations.
• Cytochrome P450 2E1 (CYP2E1, MEOS)A liver enzyme that oxidises ethanol in heavy drinkers and turns acetaminophen and other toxins into harmful products.
• Cytochrome P450 3A4 (CYP3A4)The most abundant P450 enzyme in liver and gut; it transforms about half of all drugs and is the key to many interactions.

Topics

• Transamination and deaminationThis is how amino acids lose their nitrogen: transaminases collect it on glutamate and glutamate dehydrogenase releases it as ammonia.
• One-carbon metabolism (folate, B12 and SAM)Folate and vitamin B12 move one-carbon groups to make DNA and methylate molecules; when they fail, megaloblastic anaemia and high homocysteine appear.
• Molecules derived from amino acidsBesides building proteins, amino acids give hormones, neurotransmitters, pigments and key molecules such as nitric oxide, creatine and haem.
• Glucogenic and ketogenic amino acidsDepending on where its carbon skeleton ends up, an amino acid can be used to make glucose, ketone bodies or both.
• Cori cycleIn the Cori cycle, lactate made by muscle and red cells travels to the liver, is turned back into glucose and returns to the blood.
• Glucose–alanine cycleMuscle sends its spare nitrogen to the liver as alanine; the liver turns it into urea and sends back glucose.
• Carbohydrate chemistrySugars differ by their carbonyl group, their number of carbons and the direction of their OH groups; glycosidic bonds join them together.
• Lipid chemistryLipids are water-insoluble molecules: fatty acids, triacylglycerols for energy storage, and phospholipids, sphingolipids and steroids for membranes.
• PhospholipidsPhospholipids have a phosphate head that attracts water and two fatty tails that avoid it, so they form the bilayers of every membrane.
• Sphingolipids and sphingolipidosesSphingolipids are built on ceramide and are rich in myelin and neurons; when a lysosomal enzyme that breaks them down fails, they build up.
• Membrane structureThe cell membrane is a lipid bilayer with embedded proteins that move within it, like a fluid mosaic.
• Membrane transportMolecules cross membranes by simple diffusion, through channels and carriers down a gradient, or with energy against it.
• Cell organelles and their metabolismEach organelle has its own metabolic job: mitochondria make ATP, lysosomes recycle, peroxisomes oxidise, and the ER and Golgi build.
• Lysosomal storage diseasesWhen a lysosomal enzyme is missing, the molecule it should break down stays inside, the lysosome swells and the cell eventually fails.
• Glycosaminoglycans (mucopolysaccharides)Glycosaminoglycans are long, negatively charged sugar chains that hold water and give bulk and toughness to cartilage and connective tissue.
• Mannose 6-phosphate tagging (sending enzymes to the lysosome)In the Golgi, lysosomal enzymes get a mannose 6-phosphate tag; without it they leave the cell instead of reaching the lysosome.
• Lipoprotein metabolismLipoproteins carry fat in the blood: the exogenous pathway delivers dietary fat, the endogenous pathway liver fat, and HDL returns cholesterol to the liver.
• ChylomicronChylomicrons are the largest lipoproteins: they carry dietary fat from the gut, through the lymph, to the tissues.
• VLDL (very-low-density lipoprotein)VLDL carries the triglycerides made by the liver to the tissues; as it empties it becomes IDL and then LDL.
• LDL (low-density lipoprotein)LDL delivers cholesterol to the tissues; when there is too much in the blood it settles in the arteries, hence the name "bad" cholesterol.
• HDL (high-density lipoprotein)HDL collects cholesterol from tissues and returns it to the liver (reverse transport); it also stores apolipoproteins for other particles.
• Bile acid synthesisThe liver turns cholesterol into bile acids, which help digest fat and are the body's main way out for cholesterol.
• Steroid hormone synthesis (overview)The adrenals, ovaries, testes and placenta turn cholesterol into steroid hormones; everything starts with pregnenolone.
• Acid–base interpretation (step by step)A fixed order for reading a blood gas: pH, primary cause, compensation, anion gap and mixed disorders.
• Bicarbonate–CO₂ buffer systemThe bicarbonate–CO₂ pair buffers blood acids; the lungs control CO₂ and the kidneys control bicarbonate.
• Anion gap and delta ratioThe anion gap estimates unmeasured acids and splits metabolic acidoses into two broad groups.
• Serum osmolality and osmolar gapThe difference between measured and calculated osmolality reveals extra substances in the blood, such as methanol.
• Acid–base compensation rulesFormulas that tell whether the lungs or kidneys compensated as expected or a second disorder is hiding.
• Liver function tests: reading the patternThe liver panel mixes markers of cell injury, cholestasis and true function; the pattern points to the cause.
• Aminotransferases (ALT and AST) as lab testsALT and AST leak into the blood when liver cells break; ALT is liver-specific, AST also comes from muscle.
• Alkaline phosphatase (ALP) as a lab testAlkaline phosphatase rises when bile flow is blocked or bone turns over fast; GGT tells which source it is.
• Gamma-glutamyl transferase (GGT) as a lab testGGT is very sensitive to cholestasis and alcohol but not specific; its main use is confirming that a high ALP is from the liver.
• Creatine kinase (CK) and CK-MB as lab testsCK leaks from damaged muscle; it is the key marker of rhabdomyolysis, and its MB fraction was used for heart attack before troponin.
• Cardiac troponin as a lab testCardiac troponin marks heart muscle injury; calling it a heart attack needs a rise or fall and a setting of ischaemia.
• Amylase as a lab testAmylase rises in acute pancreatitis but also from the salivary glands and other causes; lipase is now preferred.
• Lipase as a lab testPancreatic lipase is the preferred marker of acute pancreatitis: more specific than amylase and high for more days.
• Creatinine and estimated glomerular filtration rate (eGFR)Creatinine comes from muscle and is filtered by the kidney; it is used to estimate how much the glomeruli filter.
• Urea and blood urea nitrogen (BUN) as lab testsUrea is the waste form of protein nitrogen; it rises when the kidney filters less, but also with dehydration or gut bleeding.
• Serum albumin as a lab testAlbumin is the most abundant plasma protein; it falls in liver, kidney and inflammatory disease and in malnutrition.
• C-reactive protein (CRP) as a lab testCRP is a liver protein that rises within hours with inflammation or infection; it does not say where the problem is.
• Tumour markers: principles of useTumour markers help follow a cancer already diagnosed; almost none can diagnose or screen for it on its own.
• Alpha-fetoprotein (AFP)AFP is the 'fetal albumin'; in adults it rises in liver cancer and germ cell tumours, and in pregnancy it flags neural tube defects.
• Carcinoembryonic antigen (CEA)CEA is a fetal gut glycoprotein; it is used to follow colorectal cancer after treatment, not to screen for it.
• Prostate-specific antigen (PSA)PSA is a prostate enzyme; it rises in cancer but also with benign growth, infection and handling of the gland.
• CA-125CA-125 is a mucin of coelomic linings; it follows epithelial ovarian cancer but rises in many benign conditions.
• Glycated haemoglobin (HbA1c)HbA1c reflects average glucose over the past 2–3 months, because glucose sticks to haemoglobin over a red cell's life.
• Newborn screeningA few drops of heel blood detect treatable diseases before they cause harm, such as congenital hypothyroidism and PKU.
• UrinalysisUrinalysis combines appearance, dipstick and microscopy; it points to infection, kidney disease, diabetes and liver problems.
• Carnitine shuttleThe inner mitochondrial membrane does not let long-chain acyl-CoA through: carnitine carries it across in four steps.
• Odd-chain fatty acids and propionate metabolismOdd-numbered fatty acids end as propionyl-CoA, which biotin and vitamin B12 turn into succinyl-CoA.
• Peroxisomal oxidation (β- and α-oxidation)The peroxisome shortens very-long-chain fatty acids and breaks down phytanic acid, which mitochondria cannot process.
• Eicosanoids: prostaglandins, thromboxanes and leukotrienesEicosanoids are local messengers made from arachidonic acid: they control inflammation, pain, fever, clotting and airways.
• Energy requirements and basal metabolic rate (BMR)The body spends energy to stay alive at rest (BMR), to handle food and to move. A person's energy requirement is the sum of these three parts.
• Specific dynamic action (thermic effect of food)After a meal the body burns extra energy to digest, absorb, process and store the nutrients. Protein costs the most.
• Macronutrients and the energy value of foodCarbohydrates, fats and proteins supply energy: about 4, 9 and 4 kcal per gram. Alcohol gives 7 kcal per gram with no nutrients.
• Dietary fibreFibre is the part of plant food that human enzymes cannot digest. It adds bulk to stools, slows sugar absorption and helps lower cholesterol.
• Protein quality and essential amino acidsA protein is good quality when it supplies all the essential amino acids in the right amounts and is easy to digest. Mixing cereals and legumes fixes the gaps.
• Nitrogen balanceNitrogen balance compares the nitrogen eaten (as protein) with the nitrogen lost, mostly as urea. It shows whether the body is building or losing protein.
• Balanced dietA balanced diet gives enough energy for a healthy weight and every nutrient the body needs, from varied foods, with little sugar, salt and unhealthy fat.
• pH, buffers and the Henderson–Hasselbalch equationA buffer is a weak acid with its salt that soaks up added acid or base, keeping pH steady. Blood stays near pH 7.4 thanks to several buffers.
• ChromatographyChromatography separates the parts of a mixture as it flows over a material that holds each part with a different strength.
• Spectrophotometry and colorimetry (Beer–Lambert law)A coloured solution absorbs light in proportion to how much substance it contains. Measuring that absorbed light tells the concentration.
• Centrifugation and ultracentrifugationSpinning a sample very fast pushes heavier or denser particles to the bottom first. It separates blood cells, organelles and lipoproteins.
• Radioisotopes and radioimmunoassay (RIA)Radioisotopes are unstable atoms that give off radiation and can be traced. Radioimmunoassay used them to measure tiny amounts of hormones.
• Glycoproteins and protein glycosylation (N- and O-linked)Many proteins get sugar chains attached in the ER and Golgi. The sugars help folding, sorting, stability, cell recognition and blood groups.
• Protein targeting and signal sequencesEach new protein carries an 'address label' in its sequence that tells the cell where to send it: ER, nucleus, mitochondrion, peroxisome or lysosome.
• Molecular chaperones and heat shock proteinsChaperones are helper proteins that stop new or damaged proteins from clumping and help them fold. Heat and stress switch many of them on.
• Ubiquitin–proteasome systemCells mark unwanted proteins with chains of a small protein, ubiquitin. The proteasome, a barrel-shaped machine, recognises the mark and chops them up.
• Creatine, phosphocreatine and creatinineCreatine is made from three amino acids and stores quick energy in muscle as phosphocreatine. Its waste product, creatinine, shows how well the kidneys filter.
• Polyamines (putrescine, spermidine, spermine)Polyamines are small, strongly positive molecules made from ornithine. Growing cells need them, so blocking their synthesis slows parasites and some tumours.
• Purine nucleotide cycle (muscle)In working muscle, AMP is deaminated to IMP and then rebuilt. The loop keeps ATP high, feeds the Krebs cycle and releases ammonia.
• Fredrickson classification of hyperlipoproteinaemiasThe Fredrickson system sorts high blood fats into five types by which lipoprotein particle is raised. Each type points to typical causes and risks.
• Uronic acid pathwayThis side route of glucose makes UDP-glucuronic acid for detoxification and for building connective tissue. It explains why humans cannot make vitamin C.
• Lactate dehydrogenase (LDH) as a lab markerLDH is in almost every cell, so a high blood LDH means tissue damage somewhere. It is sensitive but not specific, and haemolysis in the tube raises it falsely.
• Iron metabolismThe body has no way to excrete iron: it controls how much it absorbs with hepcidin, carries it on transferrin and stores it in ferritin.
• Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)Hemoglobin changes chains from fetus to adult, and a single amino-acid change is enough to cause diseases such as sickle cell anemia.
• Fed, fasting and starvation statesThe body switches fuel with the time since the last meal: it stores in the fed state and draws on reserves while fasting.
• Insulin signallingInsulin is the fed-state hormone: it makes muscle and fat take up glucose and makes the liver store instead of release.
• Glucagon signallingGlucagon is the fasting hormone: it tells the liver to release glucose and make ketone bodies.
• G protein-coupled receptors and cAMPThe largest receptor family: the hormone binds outside, a G protein switches on inside and a second messenger amplifies the signal.
• IP₃, DAG and calcium pathwaySome hormones activate phospholipase C: IP₃ releases calcium from the reticulum and DAG activates protein kinase C.
• Receptor tyrosine kinasesReceptors that are enzymes: when they bind the hormone they phosphorylate tyrosines and switch on growth and metabolic pathways.
• JAK–STAT pathwayReceptors for cytokines and some hormones (GH, prolactin, leptin, erythropoietin) use attached JAK kinases and STAT factors.
• Nuclear receptorsFat-soluble hormones (steroids, thyroid hormone, vitamin D, retinoic acid) enter the cell and activate receptors that switch genes on or off.
• Hormone classes and mechanismsIts chemistry decides whether a hormone travels free or protein-bound and whether it acts on membrane receptors or inside the cell.
• Adrenal enzymes and congenital adrenal hyperplasiaWhich adrenal cortex enzyme makes each hormone, and what happens when one is missing: what comes before piles up and spills into another branch.
• Catecholamines: synthesis and breakdownTyrosine becomes dopamine, noradrenaline and adrenaline in four steps; the adrenal medulla releases mostly adrenaline.
• Exercise metabolismMuscle switches fuel with intensity and duration: phosphocreatine, glycogen with lactate, and then oxidised glucose and fat.
• Leptin, appetite and obesityLeptin comes from fat tissue and tells the hypothalamus how much fat there is; in obesity it is plentiful but the brain responds poorly.
• DNA structure and chromatinDNA is a double helix of two antiparallel strands held by base pairs; it wraps around histones to fit inside the nucleus.
• Central dogma of molecular biologyInformation flows from DNA to RNA and from RNA to protein; replication copies DNA and reverse transcription goes back from RNA to DNA.
• DNA replication: the replication forkTo copy DNA the double helix opens into a fork: one strand is copied continuously and the other in pieces (Okazaki fragments).
• DNA repairCells fix thousands of DNA lesions every day with several repair systems; when one fails, cancer and inherited diseases appear.
• TranscriptionTranscription copies a DNA gene into an RNA molecule; in eukaryotes three RNA polymerases do it with the help of transcription factors.
• RNA processing (cap, poly-A tail and splicing)Newly made RNA matures in the nucleus: it gets a cap and a poly-A tail and loses its introns by splicing before it leaves for the cytoplasm.
• Translation and the genetic codeIn translation the ribosome reads the mRNA three bases at a time (codons) and joins the amino acids brought by tRNAs into a protein.
• Transfer RNA (tRNA)tRNA is the adaptor of translation: it carries an amino acid at one end and, at the other, an anticodon that reads the mRNA codon.
• The lac operon and gene regulation in bacteriaThe lac operon is the classic model of how bacteria switch genes on only when needed: they use them to eat lactose when glucose runs out.
• Epigenetics: DNA and histone methylationEpigenetics means chemical marks on DNA and histones that switch genes on or off without changing the sequence, and that pass on when cells divide.
• Types of mutationsA mutation is a change in the DNA sequence; depending on where and how it happens it may do nothing, change one amino acid or ruin the whole protein.
• Trinucleotide repeat expansion disordersSome diseases come from a three-base unit repeated too many times; the repeat tends to grow from one generation to the next.
• Recombinant DNA and cloningRecombinant DNA technology cuts and joins DNA from different sources so that a host cell makes a protein or copies a gene.
• Gene therapyGene therapy treats a disease by adding, silencing or correcting a gene inside the patient's cells.
• Polymerase chain reaction (PCR)PCR copies one chosen piece of DNA millions of times in a few hours; it underpins molecular diagnosis of infections and genetic diseases.
• ELISA (enzyme-linked immunosorbent assay)ELISA detects and measures antibodies or antigens in a sample using an enzyme that makes colour when the antibody binds its target.
• Southern, Northern and Western blotsBlots separate molecules by size in a gel, move them to a membrane and detect them with a probe: DNA (Southern), RNA (Northern) or protein (Western).
• FISH (fluorescence in situ hybridization)FISH uses fluorescent DNA probes that stick to one exact place on a chromosome, to see under the microscope whether a piece is missing, extra or moved.
• DNA microarraysA microarray is a chip with thousands of DNA probes that measures the expression of many genes at once or looks for gains and losses of genetic material.
• CRISPR-Cas9 and genome editingCRISPR-Cas9 is RNA-guided 'molecular scissors' that cut DNA at an exact spot to switch off, correct or insert a gene.
• DNA sequencingSequencing means reading the exact order of DNA bases; today you can read one gene, all exons (exome) or a person's whole genome.
• Nucleotide structureA nucleotide is a nitrogenous base joined to a sugar and one or more phosphates; they build DNA and RNA and serve as the cell's energy currency.
• Drugs acting on nucleotide metabolismMany drugs against cancer, gout and transplant rejection block one specific enzyme of nucleotide synthesis or breakdown.
• Chemiosmosis and the proton gradientChemiosmosis explains how the respiratory chain and ATP synthase are linked: through a proton gradient across the inner membrane.
• Uncouplers of oxidative phosphorylationUncouplers let protons cross the inner membrane without ATP synthase: more fuel is burned, temperature rises and ATP falls.
• Mitochondrial NADH shuttlesGlycolytic NADH cannot cross the inner membrane; two shuttles carry its electrons into the mitochondrion, with different ATP yields.
• Reactive oxygen species and antioxidantsReactive oxygen species are forms of oxygen with extra electrons that damage lipids, proteins and DNA; antioxidant enzymes keep them in check.
• Amino acids: structure, charge and pKaThe 20 amino acids share one backbone and differ in their side chain; their charge changes with pH, which decides how a protein folds and migrates.
• Protein structure and foldingA protein is a chain of amino acids that folds into a precise shape; if it misfolds, it stops working or piles up and damages tissues.
• Enzyme kinetics (Michaelis–Menten and Lineweaver–Burk)An enzyme's rate rises with substrate until it reaches a maximum; two numbers, Km and Vmax, sum up how it works and how drugs change it.
• Types of enzyme inhibitionMany drugs and poisons work by slowing an enzyme; depending on where they bind, they change Km, Vmax or both, which shows on the Lineweaver–Burk plot.
• Allosteric and covalent regulation of enzymesThe cell switches its enzymes on and off within seconds using molecules that bind outside the active site or chemical changes such as phosphorylation.
• IsoenzymesIsoenzymes carry out the same reaction but are different proteins; each tissue has its own set, so in blood they reveal which organ is damaged.
• Oxygen binding: haemoglobin versus myoglobinMyoglobin stores oxygen and releases it late; haemoglobin picks it up in the lung and delivers it to tissues thanks to its S-shaped curve.
• Collagen synthesisCollagen is built in steps inside and outside the cell; each step needs an enzyme or a vitamin, and each failure causes a different disease.
• Plasma proteins and electrophoresisElectrophoresis splits serum proteins into five bands; their shape helps recognise inflammation, cirrhosis, nephrotic syndrome or myeloma.
• Cytochrome P450 systemA family of haem enzymes that oxidise drugs, toxins, hormones and vitamins; their induction and inhibition explain many drug interactions.
• Xenobiotic biotransformation: phases I, II and IIIThe body turns fat-soluble drugs and toxins into water-soluble molecules it can pass in urine or bile, in three phases.
• GlucuronidationThe most important phase II conjugation: UGT enzymes attach glucuronic acid to drugs, bilirubin and hormones so they can be excreted.
• Acetaminophen metabolism and NAPQIAt therapeutic doses acetaminophen is conjugated and excreted; in overdose those routes saturate and NAPQI destroys the liver.
• Oncogenes and tumour suppressor genesCancer arises from mutations that speed up division (oncogenes) or remove its brakes (tumour suppressors); this is the basic outline.
• Warburg effect (aerobic glycolysis in cancer)Many tumour cells burn glucose and make lactate even with oxygen present; this gives them building blocks to grow fast.
• Cobalamin (vitamin B12)Vitamin B12 contains cobalt and only two enzymes use it, but its lack causes megaloblastic anaemia and spinal cord damage.
• IronIron carries oxygen in haemoglobin and moves electrons in mitochondria; the body has no way to excrete it, so it controls absorption.
• ZincZinc is part of hundreds of enzymes and of the proteins that read DNA; it is key for growth, wound healing and fighting infection.
• CopperCopper powers enzymes that use oxygen, build collagen and melanin and move iron; two genetic diseases show its lack and its excess.
• IodineIodine is the raw material of thyroid hormones; its lack causes goitre, hypothyroidism and, in pregnancy, brain damage in the baby.
• Calcium and phosphateCalcium and phosphate form bone mineral and control nerves, muscles and energy; three hormones keep their blood levels steady.
• MagnesiumMagnesium partners ATP in almost every energy-using reaction and steadies nerves and muscles, including the heart.
• SeleniumSelenium is part of antioxidant enzymes and of the enzymes that activate thyroid hormone; both lack and excess are harmful.
• FluorideFluoride hardens tooth enamel and protects it from decay; too much in childhood stains the teeth and harms bone.

Metabolic diseases

• Ornithine transcarbamylase (OTC) deficiency
• Hyperammonaemia
• Cirrhosis
• Portal hypertension
• Phenylketonuria (PKU)
• Tyrosinaemia type I (hepatorenal)
• Alkaptonuria
• Oculocutaneous albinism
• Chronic kidney disease
• Acute kidney injury
• Helicobacter pylori gastritis
• Ischaemic stroke
• Epilepsy and seizures
• Lactic acidosis
• Pyruvate dehydrogenase deficiency
• Phaeochromocytoma
• Hypothyroidism
• Carcinoid syndrome
• Hartnup disease
• Homocystinuria
• Deep vein thrombosis
• Methylmalonic acidaemia
• Propionic acidaemia
• Viral hepatitis
• Myocardial Infarction (Heart Attack)
• Maple syrup urine disease
• Parkinson disease
• Spina bifida (myelomeningocele)
• Diabetic ketoacidosis
• Pyruvate kinase deficiency
• Tarui disease (muscle phosphofructokinase deficiency)
• Arsenic poisoning
• Type 2 diabetes mellitus
• Type 1 diabetes mellitus
• Sepsis and septic shock
• Hypovolaemic shock
• Iron deficiency anaemia
• Wernicke encephalopathy (thiamine deficiency)
• Fumarase deficiency
• Hereditary paraganglioma and pheochromocytoma (SDH)
• Fluoroacetate poisoning
• Glioblastoma
• Von Gierke disease (glycogen storage disease type I)
• Hereditary fructose intolerance
• Pompe disease (glycogen storage disease type II)
• Cori disease (glycogen storage disease type III)
• Andersen disease (glycogen storage disease type IV)
• McArdle disease (glycogen storage disease type V)
• Hers disease (glycogen storage disease type VI)
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Essential fructosuria
• Diabetic retinopathy
• Cataract
• Classic galactosaemia
• Lactose intolerance
• Cushing syndrome
• Gout
• Malaria
• Obesity
• Atherosclerosis and dyslipidaemia
• X-linked adrenoleukodystrophy
• Acute respiratory distress syndrome (ARDS)
• Gaucher disease
• Tay–Sachs disease
• Niemann–Pick disease
• Fabry disease
• Krabbe disease (globoid cell leukodystrophy)
• Metachromatic leukodystrophy
• Cystinuria
• Primary carnitine deficiency
• Zellweger syndrome (Zellweger spectrum)
• MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)
• I-cell disease (mucolipidosis II)
• Hurler syndrome (mucopolysaccharidosis type I)
• Hunter syndrome (mucopolysaccharidosis type II)
• Sandhoff disease
• Sanfilippo syndrome (mucopolysaccharidosis type III)
• Morquio syndrome (mucopolysaccharidosis type IV)
• Knee Osteoarthritis
• GM2 activator deficiency (GM2 gangliosidosis, AB variant)
• Smith–Lemli–Opitz syndrome
• Familial hypercholesterolemia
• Familial chylomicronemia syndrome (lipoprotein lipase deficiency)
• Acute pancreatitis
• Tangier disease
• Metabolic syndrome
• Gallstones (cholelithiasis)
• Abetalipoproteinemia (Bassen–Kornzweig syndrome)
• Familial dysbetalipoproteinemia (type III hyperlipoproteinemia)
• Alzheimer disease
• Crohn disease
• Adrenal insufficiency
• Polycystic ovary syndrome
• High anion gap metabolic acidosis
• Normal anion gap (hyperchloraemic) metabolic acidosis
• Metabolic alkalosis
• Respiratory acidosis
• Respiratory alkalosis
• Chronic obstructive pulmonary disease (COPD)
• Hyponatraemia
• Hypernatraemia
• Choledocholithiasis
• Gilbert syndrome
• Hepatocellular carcinoma
• Wilson disease
• Hereditary hemochromatosis
• Rickets and osteomalacia
• Primary hyperparathyroidism
• Pancreatic cancer
• Acute cholangitis
• Acute compartment syndrome
• Carnitine palmitoyltransferase II (CPT-II) deficiency
• Pulmonary embolism
• Heart failure
• Chronic pancreatitis
• Mumps
• Small bowel obstruction
• Ectopic pregnancy
• Arterial hypertension
• Autosomal dominant polycystic kidney disease
• Upper gastrointestinal bleeding
• Hypocalcaemia
• Refeeding syndrome
• Community-acquired pneumonia
• Rheumatoid arthritis
• Acute appendicitis
• Colorectal cancer
• Prostate cancer
• Ovarian cancer
• Testicular cancer
• Lung cancer
• Ulcerative colitis
• Benign prostatic hyperplasia
• Prostatitis
• Urinary tract infection (acute cystitis)
• Endometriosis
• Pelvic inflammatory disease
• Uterine fibroids (leiomyomas)
• Sickle cell disease
• Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
• Kidney stones (urolithiasis)
• Acute pyelonephritis
• Jamaican vomiting sickness (ackee poisoning)
• Refsum disease (adult)
• Asthma
• Peptic ulcer disease
• Patent ductus arteriosus
• Dysmenorrhoea
• Graves disease (hyperthyroidism)
• Kwashiorkor
• Marasmus
• Diverticular disease and diverticulitis
• Irritable bowel syndrome
• Coeliac disease
• Thalassemias (α and β)
• Methemoglobinemia
• Carbon monoxide poisoning
• Thyroid nodule
• Thyroid cancer (papillary)
• Congenital disorder of glycosylation type Ia (PMM2-CDG)
• α1-antitrypsin deficiency
• Primary hyperoxaluria
• Amyloidosis
• Prion diseases (Creutzfeldt–Jakob)
• Multiple myeloma
• Cervical cancer
• Human papillomavirus (HPV) infection
• Guanidinoacetate methyltransferase (GAMT) deficiency
• Duchenne muscular dystrophy
• Stable angina
• Erectile dysfunction
• Preeclampsia
• Myoadenylate deaminase deficiency (AMP deaminase deficiency)
• Familial combined hyperlipidaemia
• Familial hypertriglyceridaemia
• Scurvy (vitamin C deficiency)
• Crigler-Najjar syndrome
• Rhabdomyolysis
• Megaloblastic anaemia (B12 or folate deficiency)
• Infectious mononucleosis
• Pneumocystis pneumonia (PCP)
• Tumour lysis syndrome
• Acute intermittent porphyria
• Porphyria cutanea tarda
• Erythropoietic protoporphyria
• Lead poisoning
• Dubin-Johnson syndrome
• Rotor syndrome
• Neonatal jaundice
• Goitre
• Pituitary adenoma
• Breast cancer
• Adenosine deaminase deficiency (ADA-SCID)
• Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
• Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
• Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
• Anaphylaxis
• Obstructive sleep apnoea
• Gynaecomastia
• HIV infection and AIDS
• Bloom syndrome
• Xeroderma pigmentosum
• Lynch syndrome (hereditary non-polyposis colorectal cancer)
• Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)
• Ataxia-telangiectasia
• Fanconi anaemia
• Tuberculosis
• Systemic lupus erythematosus
• Fragile X syndrome
• Huntington disease
• Dengue
• Interstitial lung disease
• Lesch-Nyhan syndrome
• Hereditary xanthinuria
• Hereditary orotic aciduria
• Pleural effusion
• Multiple sclerosis
• Cyanide poisoning
• Leber hereditary optic neuropathy (LHON)
• Leigh syndrome
• Menkes disease
• Pernicious anaemia
• Pellagra (niacin deficiency)
• GM1 gangliosidosis
• Farber disease (Farber lipogranulomatosis)
• Migraine
• Osteogenesis imperfecta
• Ehlers–Danlos syndrome
• Osteoporosis
• Abdominal aortic aneurysm
• Aortic dissection
• Carpal tunnel syndrome
• Hypertensive heart disease
• Atrial fibrillation
• Intracerebral haemorrhage
• Molar pregnancy (hydatidiform mole)
• Gastric cancer
• Gastro-oesophageal reflux disease (GERD)
• Alcoholic liver disease (biochemistry)
• Disulfiram–ethanol reaction
• Methanol poisoning
• Ethylene glycol poisoning
• Oesophageal cancer
• Acetaminophen toxicity
• Vitamin A deficiency (night blindness and xerophthalmia)
• Hypervitaminosis A (vitamin A toxicity)
• Vitamin K deficiency bleeding of the newborn
• Beriberi (thiamine deficiency)
• Zinc deficiency (acrodermatitis enteropathica)
• Acute (viral) gastroenteritis
• Dental caries

Sources: RCSB PDB (CC0), PubChem (public domain), Reactome, UniProt, MedlinePlus.

Representative model, for educational purposes only.