Structures, Names, and Pathways, from Amino Acids to the Electron Transport Chain
by Professor Stephen T. Abedon Steve Abedon, Ph.D., has taught well over 100 individual classes and ~10 individual courses (including introductory biology, microbiology, physiology, biochemistry, etc.) over his 30+ years as a college professor. He has over 150 publications, including multiple monographs, and is ranked in the top 1 or 2 percent among researchers of all disciplines worldwide. His research focuses on bacteriophage biology and phage therapy. (abedon.1@osu.edu)
phage.org | phage-therapy.org | biologyaspoetry.org | abedon.phage.org | google scholar | publications
Jump to: 🗺️ Start Here | 🧬 Amino Acids | 🧩 Nucleotides | 🍬 Glycolysis | 🔄 Krebs Cycle | ⚡ Electron Transport | 🏷️ Enzyme Names | 🔍 Spot the Difference | 📖 Glossary | 🔖 Index | 🧮 More Calculators
biologyaspoetry.org/laboratories/biochemistry/ · Abedon’s Books
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Reading a list of structures is a poor way to learn them. Recognizing a structure when you see it is not the same as producing it, naming it, or knowing what an enzyme does to it. Each tab on this page therefore asks you to do something with the material: sort it, build it, predict it, or find what changed. Mistakes cost nothing here, and every question explains its answer.
The page assumes you are taking, or about to take, a college biochemistry course. It is not a textbook. It covers the structures, names, and reactions that such courses ask students to know cold, so that class time and textbook reading can go to the ideas that sit on top of them.
Textbooks disagree about how to draw biochemical structures. Some show the form a molecule actually takes in a cell, at roughly pH 7.4, with carboxyl groups as negatively charged carboxylates, amino groups as positively charged ammonium groups, and phosphates carrying negative charges. Others show every acid fully protonated and every amine neutral. Rather than pick one, this page lets you switch. The buttons above, the matching buttons at the top of each tab, and the small switch in the corner of the screen all do the same thing, and the page remembers your choice.
Watching a structure flip is itself worth doing. Pyruvic acid and pyruvate, or glutamic acid and glutamate, are not different molecules. They are the same molecule at different pH. That is why the names change along with the drawings:
Each structure shows its predominant form at pH 7.4, the one that more molecules are in than any other. A few cases deserve a note:
Names change only where common usage changes: carboxylic acids (“-ic acid” un-ionized, “-ate” ionized). Phosphate esters keep the same name either way, so “glucose 6-phosphate” is used for both forms.
Structures are skeletal (line) formulas. Every corner and line end without a label is a carbon, and hydrogens on carbon are not shown. Solid wedges point toward you and hashed wedges point away. Amino acids are drawn as their L forms, and sugars as their D forms. Ring sugars are drawn as specific anomers: glucose and glucose 6-phosphate as β-D-glucopyranose, and fructose 6-phosphate and fructose 1,6-bisphosphate as β-D-fructofuranose. Many textbooks draw sugars instead as Haworth projections, which show the same molecules as flat rings seen edge-on.
Click any tab to open it.
Your answers are kept as you go. In most browsers they are still here if you leave and come back on the same device, though a private window, a different device, or cleared browser data will start you fresh. When you are done, download a summary to hand in or keep. It lists your answers and, for each, whether it was right the first time.
The genetic code specifies twenty amino acids, and nineteen of them share the same backbone: a central carbon, the α carbon, carrying an amino group, a carboxyl group, a hydrogen, and a side chain, the R group. Proline is the exception. Its side chain loops back and bonds to the amino nitrogen, closing a five-membered ring, so its nitrogen carries one hydrogen fewer than the others’ do. Proline is sometimes called an imino acid for that reason, though strictly its nitrogen is a secondary amine, not an imine. Because it has no hydrogen on that nitrogen once it is in a protein chain, proline cannot donate the hydrogen bond that other residues use in α helices. That, together with the rigidity of its ring, is why proline so often bends or ends a helix. (Two more amino acids, selenocysteine and pyrrolysine, are built into the proteins of some organisms, including selenocysteine in humans, by reading particular stop codons in a special context.)
Apart from proline, then, learning the amino acids means learning their R groups. The grouping below follows the common textbook scheme of five groups based on the R group’s polarity and charge. Textbooks differ on where a few amino acids belong, notably glycine, cysteine, histidine, tyrosine, and tryptophan.
Twenty unrelated R groups are hard to memorize. Twenty R groups that are mostly variations on a few are easier. The table builds each amino acid from a simpler one, following the approach in the lecture below. How you memorize is up to you, though; what works for one person need not work for anyone else.
The Amino Acids, from Biology as Poetry on YouTube (open on YouTube).
| Amino acid | Build it from |
|---|---|
| glycine | Nothing: the R group is a single hydrogen. |
| alanine | A methyl group, –CH3. The starting point for most of the rest. |
| valine | A branched R group: one carbon carrying two methyl groups. |
| leucine | Valine’s branch moved one carbon farther out, by an extra –CH2–. |
| isoleucine | The same atoms as leucine, but branching at the first side-chain carbon. |
| methionine | Carbon, carbon, sulfur, carbon: –CH2–CH2–S–CH3. |
| proline | Three –CH2– groups that loop back to bond to the amino nitrogen. |
| serine | Alanine with an –OH. |
| threonine | Serine with an added methyl group on its side-chain carbon. |
| cysteine | Serine with sulfur in place of the oxygen. |
| aspartate (aspartic acid) | Alanine with a carboxyl group on the end: –CH2–COO−. |
| glutamate (glutamic acid) | Aspartate with one more –CH2–. |
| asparagine and glutamine | Aspartate and glutamate with an amide, –CONH2, in place of the side-chain carboxyl. |
| lysine | Four –CH2– groups, then an amino group (–NH3+ at pH 7.4). |
| arginine | Three –CH2– groups (A-R-G: three letters, three carbons), then the guanidinium group. |
| histidine | Alanine with a five-membered ring containing two nitrogens (imidazole), the same ring as the five-membered ring of the purines. |
| phenylalanine | Alanine with a benzene (phenyl) ring. |
| tyrosine | Phenylalanine with an –OH at the far end of the ring. |
| tryptophan | Alanine with a two-ring indole group: a five-membered ring containing a nitrogen, fused to a benzene ring. |
The structures on this page are drawn one way. Textbooks, instructors, and exams draw them in many others: turned on the page, flipped over, with the backbone running across or down, as bare lines or with every carbon and hydrogen written out, ionized or not. A structure learned as a picture can look unfamiliar the moment it is turned around. So learn what is attached to what, rather than what the drawing looks like. Find the α carbon, the one carrying both the amino group and the carboxyl group, and then read the R group outward from it.
One caution about turning drawings over. Flipping a drawing over in the plane of the page, without changing its wedges, would turn an L amino acid into its D mirror image. In the drawings below the wedges change along with the drawing, so every version is still the L form. To tell which mirror image a drawing shows, look at its wedges and hashes, not at its shape, and remember that a drawing with no wedges at all does not say which mirror image is meant.
The one-letter code was approved in 1968 by the joint IUPAC–IUB nomenclature commission, from proposals by a subcommittee that included Margaret Dayhoff, who was compiling protein sequences and needed a compact notation. The commission’s own explanations for the letters are short, and for four of them it gave none. The table separates the official reasons from the mnemonics that students have used ever since.
| Code | Amino acid | Official reason | Memory aid |
|---|---|---|---|
| C H I M S V | Cys, His, Ile, Met, Ser, Val | First letter, with no competition | — |
| A G L P T | Ala, Gly, Leu, Pro, Thr | First letter, given to the most common and simplest of the amino acids sharing it | — |
| F | Phe | Phonetic | “Fenylalanine” |
| R | Arg | Phonetic | “aRginine” |
| W | Trp | The bulky letter W for its bulky double ring | “tWyptophan” |
| K | Lys | Close in the alphabet to L | K comes just before L |
| Y | Tyr | Close in the alphabet to T | “tYrosine” |
| N | Asn | None given | “asparagiNe” |
| D | Asp | None given | “asparDic acid”; D comes before E, as Asp is one carbon shorter than Glu |
| Q | Gln | None given | “Q-tamine” |
| E | Glu | None given | “glutEmic acid” |
Most three-letter codes are simply the first three letters of the name. Four are not: Ile for isoleucine, Asn for asparagine, Gln for glutamine, and Trp for tryptophan.
The commission also explained why some letters went unused: U looks too much like V in handwriting, O is easily mistaken for several other characters on poor printouts, and J is missing from several languages. B, Z, and X were assigned to ambiguous cases: B for “Asp or Asn,” Z for “Glu or Gln,” and X for unknown.
Whether a group carries a charge depends on its pKa and the pH. When the pH is below a group’s pKa, the group holds onto its proton; when the pH is above it, the proton is mostly gone. At pH 7.4, then, groups with low pKa values have lost their protons and groups with high pKa values still have them. The values below are typical for free amino acids; they differ somewhat among textbooks, and they can shift substantially inside proteins.
| Group | Approximate pKa | At pH 7.4 |
|---|---|---|
| α-carboxyl (all amino acids) | about 2 | −COO−, negative |
| Asp side chain | 3.9 | negative |
| Glu side chain | 4.1 | negative |
| His side chain | 6.0 | mostly uncharged |
| Cys side chain | 8.3 | mostly uncharged |
| α-amino (all amino acids) | about 9 to 10 | −NH3+, positive |
| Tyr side chain | 10.1 | uncharged |
| Lys side chain | 10.5 | positive |
| Arg side chain | 12.5 | positive |
A nucleotide has three parts: a nitrogenous base, a five-carbon sugar, and one or more phosphates. Without any phosphate it is a nucleoside. Choose the parts and see what you have built, what it is called, and where it is found. Atoms of the sugar are numbered with primes (1′, 2′, 5′) to keep them apart from the atoms of the base.
The purines, adenine and guanine, have two fused rings. The pyrimidines, cytosine, thymine, and uracil, have one. A purine always pairs with a pyrimidine, so the two strands of a double helix stay the same distance apart. Adenine pairs with thymine in DNA, or with uracil in RNA, through two hydrogen bonds, and guanine pairs with cytosine through three.
NAD+ (nicotinamide adenine dinucleotide) is two nucleotides joined through their phosphates. Only the nicotinamide ring changes when NAD+ accepts electrons. It takes a hydride ion (a proton with two electrons) at the ring carbon across from the nitrogen; the ring stops being aromatic, and the nitrogen loses its positive charge. The second proton removed from the substrate goes into solution, which is why the reaction is often written NAD+ + 2 H → NADH + H+.
FAD (flavin adenine dinucleotide) works the same way with a different ring. Its working part is the three-ring flavin of riboflavin, vitamin B2, just as the nicotinamide of NAD+ comes from niacin, vitamin B3. The flavin accepts two electrons together with two protons, one at each of two ring nitrogens (N1 and N5), to become FADH2. Unlike NAD+, it can also take them one at a time, passing through a half-reduced form called a semiquinone. That is why flavins sit where a two-electron donor, such as NADH or succinate, meets the one-electron iron–sulfur clusters of Complexes I and II. The name “dinucleotide” is a little loose: the flavin half carries ribitol, an open-chain sugar alcohol, rather than a ribose ring.
Glycolysis splits one glucose into two pyruvates in ten steps, in the cytoplasm, without oxygen. The first five steps spend two ATP to make the sugar easier to split (the investment phase). The last five run twice for each glucose, once for each three-carbon half, and make four ATP and two NADH (the payoff phase). The ledger beside each step keeps the running totals for one glucose.
The enzymes are given by their full names, with the common abbreviations only alongside, because each name says what its enzyme does to which compound. Learned together, the structures, the names of the compounds, and the names of the enzymes explain one another, and the pathway becomes something you can work out rather than a list to recall. Learning abbreviations instead of names trades that understanding for memorization.
Hover over (or tap) ⚗️ The chemistry at any step to see why the step happens the way it does. You do not need it to learn the pathway, and at this level it is better not to get lost in it, but it often explains what would otherwise just have to be memorized.
In Quiz me mode, the enzyme and the product’s name are hidden, and each step asks you to name the product, the kind of reaction, and the enzyme, and to say what happens to the ledger. Tick Hide the product’s structure too to work out the product itself from the substrate and what happens to it. In Explore mode, everything is shown.
Three steps, those catalyzed by hexokinase, phosphofructokinase-1, and pyruvate kinase, release so much free energy that they are essentially irreversible in the cell. They are where glycolysis is controlled, and they are the three steps that gluconeogenesis must get around with different enzymes when it runs the pathway in reverse.
In the mitochondrial matrix, pyruvate is first converted to acetyl-CoA, losing one carbon as carbon dioxide. The cycle then joins the two-carbon acetyl group to four-carbon oxaloacetate, making six-carbon citrate, and over seven more steps removes two carbons as carbon dioxide and regenerates oxaloacetate. The cycle was worked out by Hans Krebs and William Arthur Johnson in 1937. Its energy is captured mostly as NADH and FADH2, which feed the electron transport chain, plus one GTP per turn.
Quiz me works as it does on the Glycolysis tab: name the product, the kind of reaction, and the enzyme, and say what happens to the ledger. So do the ⚗️ The chemistry notes; in the Krebs cycle especially, each step’s chemistry sets up the next.
The ledger counts one turn of the cycle, starting from one pyruvate. One glucose makes two pyruvates, so double everything for one glucose.
Notice that the two carbons that leave as carbon dioxide in one turn are not the two that entered as acetyl-CoA in that turn. Carbon atoms from acetyl-CoA are lost only in later turns.
Electrons from NADH pass through a series of carriers in the inner mitochondrial membrane before they reach oxygen. Click the carriers in the order the electrons visit them, starting with NADH.
Each carrier holds its electrons a little less tightly than the next one does. That tendency is measured as a standard reduction potential, E°′, in volts: the more positive the value, the more strongly a carrier pulls electrons toward itself. Electrons therefore run downhill, from NADH at about −0.32 V to oxygen at about +0.82 V. Three of the complexes use the energy released along the way to pump protons out of the matrix. The values shown are approximate standard values; they differ a little among sources and differ more inside a working mitochondrion.
Imagine mitochondria isolated in a buffer with ADP, phosphate, oxygen, and a fuel. Add an inhibitor. What happens to oxygen consumption, to ATP synthesis, to the proton gradient, and to the electron carriers? Make your predictions before checking them. This is the kind of reasoning that experiments with these inhibitors made possible, and it is how the order of the carriers was worked out in the first place.
The idea that a proton gradient, rather than some high-energy chemical intermediate, links electron transport to ATP synthesis is the chemiosmotic hypothesis of Peter Mitchell. Uncouplers such as 2,4-dinitrophenol were among the strongest evidence for it: they let protons back across the membrane without passing through ATP synthase, so electrons flow faster than ever while ATP synthesis stops.
Most enzyme names are a substrate followed by what the enzyme does to it, ending in “-ase.” Once you know a few dozen of those action words, most names in metabolism stop being arbitrary. “Phosphofructokinase” is the enzyme that puts a phosphate (“phospho-”) on fructose 6-phosphate (“-fructo-”) using ATP (“-kinase”). “Glyceraldehyde-3-phosphate dehydrogenase” removes hydrogens from glyceraldehyde 3-phosphate.
| Word | What the enzyme does | Examples on this page |
|---|---|---|
| kinase | Moves a phosphate from ATP (or GTP) to something else | hexokinase, phosphofructokinase-1, pyruvate kinase |
| phosphatase | Removes a phosphate by hydrolysis, using water | (the reverse direction of kinases, used in gluconeogenesis) |
| dehydrogenase | Removes hydrogens (oxidizes), handing the electrons to NAD+, NADP+, or FAD | glyceraldehyde-3-phosphate dehydrogenase, malate dehydrogenase |
| isomerase | Rearranges a molecule into an isomer | phosphoglucose isomerase, triose phosphate isomerase |
| mutase | An isomerase that moves a group, often a phosphate, to a new position in the same molecule | phosphoglycerate mutase |
| aldolase | Makes or breaks a carbon–carbon bond by an aldol reaction | aldolase (fructose-bisphosphate aldolase) |
| enolase | Named for its product, an enol, made by removing water | enolase |
| hydratase | Adds water across a double bond | fumarase (fumarate hydratase), aconitase |
| synthase | Joins molecules without using ATP directly | citrate synthase, ATP synthase |
| synthetase | Joins molecules using the energy of ATP or GTP | succinyl-CoA synthetase |
| decarboxylase | Removes CO2 | pyruvate decarboxylase (in yeast fermentation) |
| complex | Several enzymes acting together as one assembly | pyruvate dehydrogenase complex |
Every enzyme has an Enzyme Commission (EC) number whose first digit is one of seven classes. The class says what kind of reaction the enzyme catalyzes.
| EC | Class | Reaction | Example on this page |
|---|---|---|---|
| 1 | Oxidoreductases | Oxidation–reduction | malate dehydrogenase |
| 2 | Transferases | Move a group from one molecule to another | hexokinase |
| 3 | Hydrolases | Break bonds by adding water | phosphatases |
| 4 | Lyases | Break bonds without water or oxidation, often leaving a double bond | aldolase, enolase, fumarase |
| 5 | Isomerases | Rearrange a molecule | triose phosphate isomerase |
| 6 | Ligases | Join molecules using ATP or GTP | succinyl-CoA synthetase |
| 7 | Translocases | Move ions or molecules across membranes | ATP synthase |
Each question shows a reaction from glycolysis or the Krebs cycle. First decide what kind of thing the enzyme does, then build its name.
Each pair differs in one place, or in one small region. Click an atom in either structure where the two differ. Most of biochemistry happens in changes this small, and seeing them quickly is a skill worth practicing.
The named ideas used on this page, in one place. Each entry says which tab it belongs to, so this doubles as a way of finding the part you want.
A phosphate attached to a carbonyl carbon, as on carbon 1 of 1,3-bisphosphoglycerate. It gives up its phosphate more readily than ATP does, which is how glycolysis makes its first ATP.
A reaction that joins two carbonyl compounds by a new carbon–carbon bond, leaving an –OH two carbons from the carbonyl. Run in reverse, it splits such a molecule at that bond, which is what aldolase does to fructose 1,6-bisphosphate.
The central carbon of an amino acid, carrying the amino group, the carboxyl group, a hydrogen, and the R group. In every amino acid but glycine it is chiral.
The two ring forms of a sugar, which differ only at the carbon that closed the ring, the anomeric carbon. This page draws glucose and fructose phosphates as their β anomers.
A carboxylic acid with a ketone on its β carbon, the second carbon out from the carboxyl. Such acids lose CO2 easily, which is why the Krebs cycle oxidizes isocitrate before removing a carbon.
Peter Mitchell’s proposal that electron transport and ATP synthesis are linked by a gradient of protons across a membrane, rather than by a high-energy chemical intermediate.
A reaction in which a carbon next to a thioester or ester attacks a carbonyl carbon, joining the two molecules. Citrate synthase uses one to join acetyl-CoA to oxaloacetate.
A carrier of acyl groups, such as acetyl and succinyl, attached through a thioester bond to its sulfur. Drawn on this page simply as “CoA.”
Loss of a carboxyl group as CO2. In an oxidative decarboxylation, an oxidation happens at the same time, and NAD+ is reduced.
An enzyme that oxidizes its substrate by removing hydrogens, handing the electrons to NAD+, NADP+, or FAD.
The sugar of DNA: ribose without the –OH on its 2′ carbon, hence the full name 2′-deoxyribose.
An enzyme’s Enzyme Commission number. Its first digit is one of seven classes, which says what kind of reaction the enzyme catalyzes.
A carbon–carbon double bond with an –OH on one of its carbons. Enols rearrange on their own to the more stable keto form, which is the source of phosphoenolpyruvate’s high-energy phosphate.
Flavin adenine dinucleotide, a carrier of electrons built from riboflavin, vitamin B2. It accepts two electrons and two protons, one pair at a time or both together, becoming FADH2.
A change in an enzyme’s shape brought about by binding its substrate. Hexokinase, which closes around glucose, is the classic example.
Molecules made of the same atoms arranged differently, such as glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Enzymes that interconvert them are isomerases.
An enzyme that moves a phosphate from ATP, or sometimes GTP, to another molecule. Some are named for the reverse of what they do in a pathway.
The two mirror-image forms of a chiral molecule. Proteins are built from L amino acids, and the sugars of metabolism are D sugars.
An isomerase that moves a group, often a phosphate, from one position to another within the same molecule.
Nicotinamide adenine dinucleotide, a carrier of electrons built in part from niacin, vitamin B3. It accepts a hydride ion (a proton with two electrons), becoming NADH.
A base joined to a five-carbon sugar, with no phosphate. Nucleoside names end in -osine or -idine.
Making ATP with ATP synthase, driven by the proton gradient that electron transport builds. Compare substrate-level phosphorylation.
The pH at which half of a group’s molecules carry their removable proton. Below its pKa a group mostly keeps the proton; above it, it mostly loses it.
The two families of bases. Purines (adenine and guanine) have two fused rings; pyrimidines (cytosine, thymine, and uracil) have one.
The side chain of an amino acid, the only part that differs from one amino acid to the next.
How strongly a carrier pulls electrons toward itself, in volts. Electrons flow from carriers with more negative values to carriers with more positive ones.
The dependence of electron transport on ATP synthesis: when protons cannot get back through ATP synthase, the gradient builds and electron flow slows nearly to a stop.
A carbon–nitrogen double bond formed between a carbonyl and an amine. Animal aldolase forms one with a lysine of the enzyme.
A way of drawing structures in which every unlabeled corner or line end is a carbon and hydrogens on carbon are left out.
Making ATP or GTP by transferring a phosphate directly from a high-energy substrate, as phosphoglycerate kinase, pyruvate kinase, and succinyl-CoA synthetase do.
Both join molecules. A synthetase uses the energy of ATP or GTP to do it; a synthase does not.
A carbonyl carbon bonded to a sulfur, as in acetyl-CoA. A high-energy bond whose breaking can drive a reaction or make GTP.
A substance, such as 2,4-dinitrophenol, that lets protons back across the inner mitochondrial membrane without passing through ATP synthase, so that electron transport continues while ATP synthesis stops.
In a structure, a solid wedge points toward you and a hashed wedge points away. They are what distinguish mirror-image forms; a drawing without them does not say which form is meant.
A molecule carrying both a positive and a negative charge, as free amino acids do at pH 7.4: –NH3+ and –COO−.
Every section of every tab is listed below, in order, with its subsections indented beneath it. Click anything to go straight there.
There is also a search box under the tab bar, which looks through the whole page and will usually find what you want faster than scanning this will.
Building the index…