Biochemistry: Key Terms and Glossary

2,3-Bisphosphoglycerate binds the central cavity of deoxyhaemoglobin and lowers oxygen affinity; fetal haemoglobin binds it less tightly because a histidine in that cavity is serine instead.

The 2′-OH is the ribose hydroxyl that DNA lacks, and these notes use it to explain why alkali can cleave RNA and why RNA can act as a catalyst while DNA is the stabler polymer.

A-DNA is the shorter, wider right-handed helix with tilted bases, the form these notes assign to RNA duplexes and to DNA–RNA hybrids.

The active site is the cleft of side chains, sometimes with a cofactor, that the fold places so the enzyme binds one reaction’s transition state more tightly than the substrate.

Anaplerosis is any reaction that refills a citric-acid-cycle intermediate drained off into biosynthesis, so that acetyl-CoA still has an acceptor.

Anfinsen’s ribonuclease result showed that the amino-acid sequence itself specifies the native fold, including the correct disulphides, once the chain is allowed to search ordinary solvent.

The anion gap is the excess of unmeasured anions over the usual electrolyte tally, and it widens in ketoacidosis because dissociated ketone bodies are not counted in that tally.

An anomer is one of the two configurations, α or β in the D series, at the new stereocentre formed when a sugar carbonyl closes on a hydroxyl of the same molecule.

ATCase is *E. coli* aspartate transcarbamoylase, whose catalytic and regulatory subunits can be separated, with CTP stabilising the low-affinity T state and ATP the high-affinity R state.

B-DNA is the ordinary cellular duplex: right-handed, with about 10.5 base pairs per turn in solution, a rise of about 0.34 nm, and base pairs nearly perpendicular to the axis.

Bicarbonate is the open blood buffer, with an effective pKa near 6.1, that still holds plasma near pH 7.4 because ventilation fixes dissolved CO2; the same ion is consumed when ketone acids dissociate.

A bilayer is the sheet formed by cylindrical, two-tailed lipids, and it closes on itself so that free edges do not leave tails in water.

Binding change is the rotary cycle in which the three catalytic sites pass through open, loose, and tight states, the proton-motive force paying for release of tightly bound ATP and for binding of ADP and phosphate.

The Bohr effect is the shift of haemoglobin towards the low-affinity T state when pH falls or PCO2 rises, so working tissue unloads more oxygen.

Carbamoyl phosphate synthetase I spends two ATP in the mitochondrial matrix to make carbamoyl phosphate from ammonia and bicarbonate, and it requires N-acetylglutamate; it is not the cytosolic synthetase of pyrimidine synthesis.

Carbonic anhydrase makes hydration of CO2 fast in the red cell, so the open bicarbonate buffer can respond on a physiological timescale.

Carnitine palmitoyltransferase I, on the outer mitochondrial membrane, swaps CoA for carnitine on a fatty acyl chain so the acyl group can enter the matrix, and malonyl-CoA inhibits it.

Cellulose is linear β-1,4 glucose, a straight hydrogen-bonded fibre that humans cannot digest because they have no cellulase for that linkage.

A chaperone binds exposed hydrophobic stretches so that a chain in a crowded cell is less likely to aggregate, and it does not supply folding information missing from the sequence.

Chargaff, as used here, names the equalities of adenine with thymine and guanine with cytosine in double-stranded DNA, while the ratio of those pairs to each other is not fixed.

Chemiosmosis is Mitchell’s account of oxidative phosphorylation: electron transport and ATP synthesis meet only through proton flow across a closed membrane, not through a shared chemical intermediate.

Chitin is the β-1,4 polymer of N-acetylglucosamine, the same straight geometry as cellulose with a different sugar, used in fungal walls and arthropod cuticle.

Cholesterol is the compact four-ring lipid that restrains chains above the transition temperature and blocks them from freezing into a gel below it.

A chylomicron is the intestinal lipoprotein, marked by apoB-48, that carries dietary triacylglycerol into the blood by way of the lymph.

Cis unsaturation is a cis double bond in a fatty acyl chain, which kinks packing and lowers the melting temperature relative to the saturated acid.

Citrate synthase condenses acetyl-CoA with oxaloacetate and water to citrate; hydrolysis of the citryl-CoA intermediate pulls the reaction, and ATP is not consumed.

A cofactor is a metal or an organic group, often derived from a vitamin, that carries chemical steps amino-acid side chains cannot manage on their own.

Competitive inhibition means the inhibitor binds free enzyme rather than the enzyme–substrate complex, so apparent Km rises and enough substrate can still reach the original Vmax.

Complexes I–IV are the inner-membrane respiratory enzymes; in the usual count of these notes, I, III, and IV move about four, four, and two protons per electron pair, and II moves none.

The Cori cycle returns lactate from muscle or red cells to the liver for gluconeogenesis, and the liver spends six ATP equivalents to remake glucose that yielded only two ATP in the periphery.

Cortisol is the slower hormone of stress and prolonged fasting; it raises the amounts of gluconeogenic enzymes and supports muscle protein breakdown, and it restrains glucose uptake in several tissues.

Cytochrome c is the small peripheral haem protein that carries one electron at a time from complex III to complex IV.

Linoleate and α-linolenate are the essential fatty acids in these notes, required in the diet because mammals cannot introduce double bonds beyond Δ9.

F0 is the membrane portion of ATP synthase, including the c-ring that returning protons turn.

F1 is the catalytic head of ATP synthase in the matrix, whose β subunits make ATP as the rotating shaft changes their conformation.

FAD, usually bound as a prosthetic group, can accept one electron or two and delivers them at a more positive potential than NADH, which is why succinate reduces ubiquinone rather than NAD+.

Flip-flop is the uncatalysed movement of a lipid from one leaflet to the other, slow because the polar head must cross the hydrocarbon core.

Fructose 1,6-bisphosphatase hydrolyses fructose 1,6-bisphosphate to fructose 6-phosphate, the bypass of phosphofructokinase-1 in gluconeogenesis.

Fructose 2,6-bisphosphate is a regulator, not a glycolytic intermediate, that turns phosphofructokinase-1 on and fructose 1,6-bisphosphatase off; glucagon lowers it in liver.

Glucagon is the fasted-state hormone of the pancreatic α cells, read mainly by liver, which has no glucagon receptor on muscle, and it promotes hepatic glycogen breakdown, gluconeogenesis, and fat oxidation.

Glucogenic describes an amino acid whose carbon skeleton can become pyruvate or a four- or five-carbon cycle intermediate and therefore support net glucose; leucine and lysine, ketogenic only in these notes, cannot.

Gluconeogenesis is the making of glucose from lactate, glycerol, and glucogenic amino acids by bypassing the irreversible steps of glycolysis, not by running that pathway backwards.

Glucose 6-phosphatase hydrolyses glucose 6-phosphate to free glucose in liver and kidney; muscle and brain lack it and cannot release glucose into the blood.

Glucose 6-phosphate dehydrogenase is the first enzyme of the oxidative pentose phosphate pathway, and the red cell depends on the NADPH it makes to keep glutathione reduced.

GLUT2 is the high-Km glucose transporter of liver, which insulin does not translocate, so hepatic glucose uptake follows the concentration in the blood.

GLUT4 is the glucose transporter that insulin moves to the surface of muscle and adipose tissue.

Glutamate dehydrogenase frees ammonium from glutamate in the mitochondrial matrix, the step that sends most collected amino-acid nitrogen towards urea.

Glutathione is the cysteine-containing tripeptide that reduces peroxides in the red cell and is restored to its thiol form by NADPH.

Glycogen is the branched storage polymer of glucose, α-1,4 chains with α-1,6 branches about every 8–12 residues, so many non-reducing ends can be used at once.

Glycogen synthase adds the glucose of UDP-glucose to a non-reducing end as an α-1,4 link, and phosphorylation by protein kinase A switches it off.

A glycosidic bond joins the anomeric carbon to an alcohol, another sugar, or a nitrogen, locking that anomer so the ring can no longer open freely.

The glyoxylate cycle converts two acetyl-CoA into a four-carbon acid by skipping the two decarboxylations of the citric acid cycle; animals lack it, so even-chain acetyl-CoA is not a net source of glucose.

Group-transfer potential is the free energy of hydrolysis used as a rank order, so a donor higher on the scale can phosphorylate an acceptor lower down.

A hairpin is a short A-form stem of Watson–Crick pairs closed by a loop of unpaired bases, the usual folding unit of a single RNA strand.

HDL picks cholesterol up from cell membranes and returns it to the liver, the opposite direction of travel from LDL.

The Henderson–Hasselbalch equation, pH = pKa + log10([A−]/[HA]), converts a buffer ratio into pH and shows why capacity collapses once that ratio is far from 1.

HGPRT salvages hypoxanthine to IMP and guanine to GMP, each with PRPP; without it, PRPP rises, de novo purine synthesis accelerates, and uric acid is overproduced.

Histidine is the side chain whose pKa lies near neutrality, which is why it accounts for most protein buffering around pH 7 and is often only partly protonated in active sites.

HMG-CoA reductase reduces cytosolic HMG-CoA to mevalonate, the committed step of cholesterol synthesis, and it is a different enzyme from the mitochondrial HMG-CoA route of ketogenesis.

Hormone-sensitive lipase is the adipose enzyme that prefers diacylglycerol and is switched on by phosphorylation when glucagon or adrenaline raises cAMP.

A hydrogen bond is the attraction between a partially positive hydrogen and a lone pair, which lets water dissolve ions and polar metabolites and is also used inside proteins and nucleic acids.

The hydrophobic effect, at physiological temperature, is largely the gain in solvent entropy when nonpolar surfaces cluster and free ordered water, not a long-range attraction between the hydrocarbons.

The hyperchromic effect is the rise in ultraviolet absorbance near 260 nm when bases unstack as a duplex melts.

Induced fit is closure of the active site around the substrate so that catalytic groups line up for the transition state and water is excluded, not a tighter grip on the ground state as catalysis in itself.

Insulin is the fed-state hormone of the pancreatic β cells; it promotes glucose uptake through GLUT4, glycogen and fat storage, and liver glycolysis, and it restrains gluconeogenesis, lipolysis, and ketogenesis.

kcat is the turnover number, Vmax divided by the enzyme concentration, the maximum number of product molecules each active site can make per second.

Keq is the equilibrium constant; a value greater than 1 means ΔG°′ is negative, which still leaves the sign of the cellular ΔG dependent on concentrations.

Ketoacidosis is the metabolic acidosis of absent insulin, in which unrestrained lipolysis drives hepatic ketone acids that consume bicarbonate even though blood glucose is already high.

Ketogenesis is the hepatic production of ketone bodies from acetyl-CoA when β-oxidation runs ahead of the citric acid cycle, as in fasting and when insulin is absent.

A ketone body is acetoacetate or D-3-hydroxybutyrate, or the acetone that acetoacetate can lose, made in liver mitochondria when acetyl-CoA exceeds the citric acid cycle; the liver cannot oxidise the acids it exports.

Km is the substrate concentration at half Vmax, and it equals a dissociation constant only in the limit where the catalytic step is much slower than substrate leaving the enzyme.

Kw is the ion-product [H+][OH−] of water, 1.0 × 10−14 at 25°C, so neutrality is pH 7 at that temperature and a little below 7 at body temperature.

Lactate dehydrogenase reduces pyruvate to lactate and returns NAD+, so glycolysis can continue when the respiratory chain is not reoxidising NADH.

LDL is the cholesterol-ester-rich particle produced from VLDL that delivers cholesterol to tissues and back to the liver through the receptor that recognises apoB-100.

The Lineweaver–Burk plot is the double-reciprocal graph of the Michaelis–Menten equation, still used to recognise inhibition patterns and a poor way to estimate constants because the noisiest low-substrate points are exaggerated.

Lipoamide is the disulphide on a flexible lysyl arm of pyruvate dehydrogenase that carries the acyl group between the active sites of the complex.

The major groove is the wider groove of a duplex, wide enough for a protein to read the edge pattern of the bases without separating the strands.

The malate–aspartate shuttle carries reducing power from cytosolic NADH into matrix NADH, so the electrons enter at complex I and are worth about 2.5 ATP, rather than about 1.5 ATP when the electrons reach ubiquinone instead.

Malonyl-CoA is the product of acetyl-CoA carboxylase, the two-carbon donor for fatty-acid synthesis, and it also shuts carnitine palmitoyltransferase I so synthesis and mitochondrial oxidation do not run together.

The methyl trap is the pile-up of folate as methyl-tetrahydrofolate when B12-dependent methionine synthase cannot pass the methyl group on, so other one-carbon reactions starve even if total folate looks adequate.

A micelle is the sphere formed by conical, single-tailed amphiphiles, with tails inside and no water-filled compartment.

Mutarotation is the equilibration, in water, of the open-chain sugar with its α and β ring forms.

N-Acetylglutamate is the obligate activator of carbamoyl phosphate synthetase I, and arginine stimulates the synthase that makes it.

N-linked describes a glycan attached through N-acetylglucosamine to the side-chain nitrogen of asparagine in a sequon.

NAD is the nicotinamide cofactor that accepts a hydride in catabolism, and the cell keeps the NAD+/NADH ratio high so that fuels can be oxidised.

NADP carries hydride by the same chemistry as NAD but with an extra phosphate, and its pool is kept mostly reduced to supply NADPH for biosynthesis.

Pure non-competitive inhibition binds free enzyme and the enzyme–substrate complex equally, leaving Km unchanged while Vmax falls; binding the two forms unequally is the mixed pattern these notes keep separate.

O-linked describes sugars built on the side-chain oxygen of serine or threonine, without the single sequon used for N-linked glycans.

Oligomycin blocks proton return through F0, so the gradient rises and electron transport slows even though the respiratory chain itself is intact.

P/O is the ATP formed per pair of electrons passed to oxygen; these notes use about 2.5 for mitochondrial NADH and about 1.5 for FADH2, and they treat about 30 ATP per glucose as an estimate that depends on the shuttle, not as a fixed constant.

PEPCK decarboxylates and phosphorylates oxaloacetate to phosphoenolpyruvate at the cost of GTP, completing the bypass of pyruvate kinase.

A peptide bond is the planar amide that joins amino acids; partial double-bond character confines backbone rotation to the two bonds around the α-carbon.

Phosphatidate is glycerol with fatty acyl chains at C1 and C2 and a phosphate at C3, the parent structure of the glycerophospholipids.

A phosphoanhydride is the linked-phosphate arrangement in ATP whose hydrolysis is favourable because the products are more stable, not because the bond stores energy like a loaded spring.

A phosphodiester is the 3′,5′ linkage of a nucleic-acid backbone, negatively charged near pH 7, which gives every chain a 5′ end and a 3′ end.

Phosphofructokinase-1 transfers a phosphate from ATP to fructose 6-phosphate and is the principal control point of glycolysis, inhibited by ATP and citrate and activated by AMP and fructose 2,6-bisphosphate.

Phosphorylase kinase, activated by protein kinase A and by calcium–calmodulin, phosphorylates glycogen phosphorylase and converts it to the active a form.

pKa is −log10 of the acid dissociation constant, and it is the pH at which the acid and its conjugate base are equal and buffering is strongest.

The proton-motive force is the electrochemical gradient of protons across the inner membrane, membrane potential plus the pH difference, that links electron transport to ATP synthesis.

Pyridoxal phosphate is the vitamin B6 prosthetic group of aminotransferases; it holds the amino acid as a Schiff base so the amino group can be moved without free ammonia appearing.

Pyrophosphatase hydrolyses inorganic pyrophosphate, ΔG°′ about −19 kJ/mol in these notes, and thereby pulls reactions that have split ATP as far as AMP.

Pyruvate carboxylase is the biotin enzyme that carboxylates pyruvate to oxaloacetate when acetyl-CoA is high, both to refill the citric acid cycle and to bypass pyruvate kinase in gluconeogenesis.

Pyruvate dehydrogenase kinase phosphorylates the E1 subunit and switches the complex off when NADH, acetyl-CoA, and ATP are already abundant.

The Q cycle is the complex III route that splits the electrons of quinol, one towards cytochrome c and the other back through the membrane, so that protons appear on the outer face.

The R state is the high-affinity conformation of haemoglobin that oxygen binding favours once the bridges that hold the T state have broken.

Ramachandran angles are φ and ψ, the two backbone rotations still allowed by a planar peptide, and regular helices and strands occupy narrow regions of that map.

A reducing sugar still has a free anomeric carbon that can open to an aldehyde; if every anomeric carbon is tied up in a glycosidic bond, the sugar is non-reducing.

The reduction potential ranks a redox couple so that electrons move towards the more positive partner, which is why NADH can reduce oxygen and succinate cannot reduce NAD+.

Ribonucleotide reductase reduces ribonucleoside diphosphates to deoxyribonucleotides, and an activity site turns the animal enzyme on with ATP and off with dATP.

A sequon is the local sequence Asn–X–Ser/Thr, X not proline, that marks an asparagine for attachment of an N-linked glycan.

The specificity constant is kcat/Km, the number that decides which of two competing substrates is preferred when both are well below their Km.

Sphingomyelin is ceramide carrying phosphocholine, a sphingolipid that these notes place with phosphatidylcholine in the outer leaflet.

Stacking is the contact between neighbouring aromatic bases, which these notes treat as the larger share of duplex stability, while the hydrogen bonds specify which base is allowed.

A statin is a competitive inhibitor of HMG-CoA reductase; hepatic cholesterol synthesis falls, and the liver responds by displaying more LDL receptors and clearing more LDL from blood.

Substrate-level phosphorylation makes ATP or GTP by direct transfer from a metabolic intermediate, as in the phosphoglycerate kinase step, rather than from the respiratory proton gradient.

Sucrose is glucose joined α1→2 to β-fructose, and it is non-reducing because both anomeric carbons lie in that one bond.

The T state is the low-affinity conformation of haemoglobin, braced by salt bridges, and it is the form stabilised by protons, CO2, and 2,3-bisphosphoglycerate.

Tetrahydrofolate is the folate cofactor that carries one-carbon units at several oxidation levels for thymidylate synthesis and for two steps of purine synthesis.

Thymidylate synthase methylates dUMP to dTMP and, unlike the other folate reactions in these notes, leaves the cofactor as dihydrofolate, which must be reduced again before the pool can continue.

Tm is the temperature at the midpoint of strand separation, raised by GC content and by salt and lowered by mismatches, shorter duplexes, or a denaturing solvent.

TPP is thiamine pyrophosphate, the cofactor whose thiazolium ring stabilises the acyl carbanion in the first step of pyruvate dehydrogenase.

The transition state is the high-energy arrangement whose free energy, relative to the substrate, the enzyme lowers, speeding both directions of the reaction without changing Keq.

The transition temperature is the point at which membrane lipids pass between gel and fluid packing; cis double bonds lower it and longer saturated chains raise it.

A triacylglycerol is glycerol esterified with three fatty acids, a headgroup-free store that forms droplets rather than bilayers, and these notes give fat about 38 kJ/g against about 17 kJ/g for carbohydrate.

UCP1 is the regulated uncoupling protein of brown adipose tissue, which lets protons re-enter without ATP synthase so the proton-motive force is spent as heat.

Uncompetitive inhibition means the inhibitor binds the enzyme–substrate complex and not free enzyme, so apparent Km and Vmax both fall and extra substrate does not displace it.

Urea is the excreted end product that carries two nitrogens, one from free ammonia and one from aspartate, together with the carbon of bicarbonate, at a cost of four high-energy phosphate bonds in these notes.

Watson–Crick pairing is adenine with thymine by two hydrogen bonds and guanine with cytosine by three, pairs of equal width that fit an antiparallel duplex.

Z-DNA is a left-handed duplex with a zigzag backbone, a local form favoured by alternating purine–pyrimidine sequence under negative supercoiling or high salt, not the default helix.

A zymogen is an inactive precursor switched on by peptide cleavage, a change these notes contrast with phosphorylation because it cannot be undone in place when the signal falls.

An α helix, in these notes, is a right-handed coil in which each backbone carbonyl hydrogen-bonds to the N–H four residues ahead, with about 3.6 residues per turn and side chains pointing outwards.

A β sheet is a set of extended strands hydrogen-bonded to one another, with side chains alternating above and below the sheet.

A β turn reverses the polypeptide in about four residues, commonly with a hydrogen bond from residue i to i+3, and it is rich in glycine and proline.

β-Oxidation is the mitochondrial spiral that shortens an acyl-CoA by two carbons at each round, releasing acetyl-CoA and reducing both FAD and NAD+.

ΔG is the free-energy change at the concentrations actually present, equal to ΔG°′ plus RT ln Q, and it is the sign of ΔG, not of the standard value, that decides whether a step can run forward.

ΔG°′ is the standard free-energy change at pH 7, equal to −RT ln Keq; these notes give ATP hydrolysis about −30.5 kJ/mol on that scale, against a typical cellular ΔG of about −50 to −60 kJ/mol.