FCPS Part 1 biochemistry: the high-yield guide
Biochemistry questions reward a small set of facts asked again and again: rate-limiting enzymes, vitamin cofactors, inborn errors and a handful of lab techniques. Learn those as pairs.
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Why biochemistry feels harder than it is
Biochemistry has a reputation for endless pathways. In the paper, the pathways almost never appear as full diagrams. What appears is a single link in the chain: the enzyme that controls a pathway, the vitamin an enzyme needs, the disease that follows when one enzyme is missing.
So the subject shrinks once you stop trying to draw glycolysis from memory and start learning it as pairs:
- pathway to rate-limiting enzyme
- enzyme to vitamin cofactor
- missing enzyme to disease and its one striking sign
- drug to enzyme it blocks
Rate-limiting enzymes
Learn this table until you can recite it backwards. It carries more marks per minute than anything else in biochemistry.
| Pathway | Rate-limiting enzyme |
|---|---|
| Glycolysis | Phosphofructokinase-1 |
| Gluconeogenesis | Fructose-1,6-bisphosphatase |
| TCA cycle | Isocitrate dehydrogenase |
| Glycogen synthesis | Glycogen synthase |
| Glycogen breakdown | Glycogen phosphorylase |
| HMP shunt | Glucose-6-phosphate dehydrogenase |
| Fatty acid synthesis | Acetyl-CoA carboxylase |
| Fatty acid oxidation | Carnitine palmitoyltransferase I |
| Ketogenesis | HMG-CoA synthase |
| Cholesterol synthesis | HMG-CoA reductase (statins) |
| Urea cycle | Carbamoyl phosphate synthetase I |
| Haem synthesis | ALA synthase |
| Purine synthesis | Glutamine-PRPP amidotransferase |
| Pyrimidine synthesis | Carbamoyl phosphate synthetase II |
| Catecholamine synthesis | Tyrosine hydroxylase |
Two common traps: CPS I is in the urea cycle (mitochondria), CPS II is in pyrimidine synthesis (cytoplasm). And the liver makes ketones but cannot use them.
Vitamins: cofactor and deficiency
Vitamin questions come in two shapes. Either the stem describes a deficiency and asks for the vitamin, or it names an enzyme and asks for its cofactor.
| Vitamin | Works as | Deficiency picture |
|---|---|---|
| B1 thiamine | Pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, transketolase | Beriberi, Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia) |
| B2 riboflavin | FAD, FMN | Angular stomatitis, cheilosis, magenta tongue |
| B3 niacin | NAD, NADP | Pellagra: dermatitis, diarrhoea, dementia |
| B6 pyridoxine | Transamination, ALA synthase, decarboxylation | Neuropathy (isoniazid), sideroblastic anaemia, infant seizures |
| B12 | Methionine synthase, methylmalonyl-CoA mutase | Megaloblastic anaemia with neurological damage |
| Folate | One-carbon transfer, thymidine synthesis | Megaloblastic anaemia, neural tube defects |
| Biotin | Carboxylases | Dermatitis, alopecia (raw egg whites) |
| Vitamin C | Collagen hydroxylation | Scurvy: bleeding gums, perifollicular haemorrhage, corkscrew hairs |
| Vitamin K | γ-carboxylation of II, VII, IX, X, proteins C and S | Bleeding with prolonged PT |
The single most tested contrast: B12 deficiency raises methylmalonic acid; folate deficiency does not. Both raise homocysteine.
The second: in a confused alcoholic, give thiamine before glucose.
Inborn errors that repeat
You do not need every rare disease. You need the ones that come with a clue the examiner can put in one line.
| Disorder | Missing enzyme | The clue |
|---|---|---|
| Phenylketonuria | Phenylalanine hydroxylase | Musty odour, fair skin, intellectual disability |
| Alkaptonuria | Homogentisate oxidase | Urine turns black on standing, dark ear cartilage |
| Maple syrup urine disease | Branched-chain keto acid dehydrogenase | Sweet urine, sick neonate |
| Homocystinuria | Cystathionine β-synthase | Lens dislocates downwards, thrombosis, marfanoid |
| Von Gierke (GSD I) | Glucose-6-phosphatase | Severe fasting hypoglycaemia, big liver, lactic acidosis |
| Pompe (GSD II) | Lysosomal acid maltase | Big heart in an infant |
| McArdle (GSD V) | Muscle phosphorylase | Exercise cramps, no lactate rise |
| Galactosaemia | Galactose-1-phosphate uridyltransferase | Jaundice, cataracts, E. coli sepsis |
| Hereditary fructose intolerance | Aldolase B | Hypoglycaemia after fruit or sugar |
| Tay–Sachs | Hexosaminidase A | Cherry-red spot, no hepatosplenomegaly |
| Niemann–Pick | Sphingomyelinase | Cherry-red spot with hepatosplenomegaly |
| Gaucher | Glucocerebrosidase | Bone crises, big spleen, "crumpled paper" cells |
| Lesch–Nyhan | HGPRT | Self-mutilation, gout |
Inheritance is a frequent second question on the same stem. Most enzyme defects are autosomal recessive. The X-linked exceptions worth remembering are Fabry, Hunter, Lesch–Nyhan, G6PD deficiency and ornithine transcarbamylase deficiency.
Enzyme kinetics in one picture
Kinetics questions are almost always about how an inhibitor changes Km and Vmax.
| Inhibitor | Km | Vmax | Example |
|---|---|---|---|
| Competitive | Rises | Unchanged | Methotrexate on DHFR, statins, ethanol for methanol poisoning |
| Non-competitive | Unchanged | Falls | Heavy metals |
| Irreversible | — | Falls | Aspirin on COX, organophosphates, omeprazole |
Remember that Km is inversely related to affinity. A low Km means the enzyme grabs its substrate tightly.
Lipoproteins and dyslipidaemias
- Chylomicrons carry dietary fat (apo B-48). LDL carries cholesterol to tissues (apo B-100). HDL brings cholesterol back to the liver (apo A-I).
- Lipoprotein lipase needs apo C-II. Its deficiency causes massive chylomicronaemia and pancreatitis, not heart disease.
- Familial hypercholesterolaemia is an LDL receptor defect. The clue is tendon xanthomas in a young person with early heart disease.
- Statins work mainly by increasing hepatic LDL receptors.
Molecular techniques
These are easy marks if you learn one line for each.
- Southern blot detects DNA, Northern detects RNA, Western detects protein.
- PCR runs denature (about 94 °C), anneal, then extend (about 72 °C) with heat-stable Taq polymerase.
- RT-PCR is for RNA viruses, because reverse transcriptase makes DNA first.
- FISH finds microdeletions such as 22q11 that a karyotype misses.
- ELISA is sensitive, so it is used for screening.
Common traps
- Glucokinase (liver, high Km) is not inhibited by its product. Hexokinase (other tissues, low Km) is.
- Muscle lacks glucose-6-phosphatase, so muscle glycogen cannot raise blood glucose.
- Leucine and lysine are the only purely ketogenic amino acids.
- Lead blocks ALA dehydratase and ferrochelatase, giving basophilic stippling and microcytic anaemia.
- Cyanide and carbon monoxide both act on complex IV. Uncouplers such as high-dose aspirin increase heat and oxygen use but stop ATP production.
How to revise biochemistry in 10 days
- Days 1 to 2: rate-limiting enzymes and the vitamin table. Write both out from memory each morning.
- Days 3 to 4: carbohydrate and lipid metabolism, including the glycogen storage diseases and dyslipidaemias.
- Days 5 to 6: amino acids, urea cycle and the inborn errors table.
- Day 7: haem, porphyrias and iron.
- Day 8: nucleotides, DNA replication, repair defects and molecular techniques.
- Days 9 to 10: mixed question sets, then rewrite every pair you got wrong on one page.
Practise these in the FCPS-1 Prep question bank. Every biochemistry question links to a full topic review, so a missed enzyme leads straight to the whole pathway.
Read next: Physiology high-yield · Pharmacology high-yield · Haematology high-yield
Frequently asked questions
Do I need to memorise full pathways for FCPS Part 1?
No. Learn the controlling enzyme, the cofactors and what happens when an enzyme is missing. Full diagrams are rarely asked.
Which vitamin topics come most often?
B12 versus folate, thiamine in alcoholics, vitamin K and clotting, vitamin D metabolism and vitamin A deficiency signs.
Is molecular biology worth studying?
Yes, briefly. The blots, PCR steps, FISH and the DNA repair diseases are short topics that appear regularly.