BIOL 2021 · Molecular Cell Biology
Midterm 1 — Study Guide
Everything for Midterm 1 in one place: six topic guides (Topics 2–6) with instant-feedback practice built into every topic, plus a 120-question mock exam. Content is lecture-scoped and verified against Alberts, Molecular Biology of the Cell , 7th ed. Expand any concept below for a cheat sheet: what to know and what to memorize .
Scope: Topics 2–6 + Midterm 1 Mock ExamMidterm 2: ~2 weeks outFinal: ~4 weeks out
✦ Topics & Cheat SheetsEach section links straight into the guide. Tap Expand all cheat sheets
Ch. 1 · the universal cell, the tree of life, endosymbiosis
Know
All cells share four things: DNA storage, transcription→translation, a plasma membrane, and ATP as energy currency. Templated polymerization is one mechanism reused three times (DNA→DNA, DNA→RNA, RNA→protein). The genetic code is a “frozen accident” (arbitrary), so its universality is evidence of common descent from LUCA. Memorize
LUCA · central dogma directionality (never protein→nucleic acid, except RNA→DNA in retroviruses) The 3 uses of templated polymerization ~525 genes = minimal-cell estimate (Mycoplasma) Know
Cells are small because diffusion is only fast over short distances, and surface-area-to-volume limits exchange. Resolution, not magnification, is the real microscopy limit. Memorize
Bacterium ~1–2 µm · animal cell ~10–30 µm Light-microscope resolution ~0.2 µm; EM resolves to nm µm vs nm order of magnitude Know
Eukaryotes have a nucleus + membrane-bound organelles; prokaryotes have neither. The nucleus separates transcription (nucleus) from translation (cytosol), permitting RNA processing. Cell walls differ by lineage — this is a favourite MCQ distinction. Memorize
Nucleus, ER, Golgi, mitochondria = eukaryote-only Walls: bacteria peptidoglycan · plants cellulose · fungi chitin Compartmentalization Know
Woese used rRNA to define Bacteria, Archaea, Eukarya; Archaea are closer to Eukarya than to Bacteria. Homology = shared ancestry; orthologs (speciation) vs paralogs (duplication); HGT moves individual genes, not whole decoding systems. Memorize
3 domains · rRNA (16S/18S) as the molecular ruler Archaea⟷Eukarya sisterhood Horizontal gene transfer (HGT) Know
Trophic category = (energy source: photo/chemo) × (carbon source: auto/hetero). Extremophiles occupy defined niches along steep gradients; each band hosts distinct organisms. Memorize
photoautotroph / chemoautotroph / photoheterotroph / chemoheterotroph Vent core ~350 °C (textbook; lecture’s 380 is wrong) N-fixation and C-fixation Know
Mitochondria came first (aerobic bacterium engulfed by an archaeal host); chloroplasts second (cyanobacterium into a cell that already had mitochondria). Evidence: double membrane, own circular DNA, own 70S (bacterial) ribosomes, binary fission. Memorize
Margulis 1967 (NOT 1981) Human mtDNA 16,569 bp, 13 proteins Order: mito → chloroplast · glycolysis is CYTOSOLIC, not mitochondrial Know
Fungi (chitin walls, absorptive feeders) and protozoa (single-celled eukaryotes) are eukaryotic microbes. Model organisms are studied because shared descent makes findings transferable. Memorize
Plasmodium = protozoan (NOT a virus) C. elegans = 959 somatic cells Gene counts don’t track complexity (Arabidopsis > human) Know
Viruses are not cells and not alive — no metabolism, obligate intracellular parasites. Structure = genome + capsid (± envelope); retroviruses reverse the flow via reverse transcriptase. Memorize
Capsid · obligate intracellular parasite Reverse transcriptase (RNA→DNA) DNA vs RNA viruses; some cause cancer Know
Astrobiology asks what non-Earth life might look like and how we’d detect it (biosignatures). Extremophiles set the boundaries of habitability and guide where to look. Memorize
Biosignature Targets: Mars, Europa, Enceladus Ch. 10 · the bilayer, fluidity, proteins, rafts
Know
Membranes self-organize because hydrophobic tails avoid water; the driving force is the hydrophobic effect. It is ENTROPY-driven (water minimizes ordered cage formation) — not an attractive “hydrophobic bond.” Memorize
Amphipathic (hydrophilic head + hydrophobic tail) Entropy-driven, NOT enthalpy/“bond” Phospholipid as the building block Know
Molecular shape decides the structure: cylindrical lipids → bilayers, cone-shaped → micelles. Bilayers are self-sealing; torn edges reseal to bury tails (they don’t form hemi-micelle caps). Memorize
Bilayer / micelle / liposome Self-assembly is spontaneous Edges reseal to avoid tail exposure Know
Fluidity rises with temperature, unsaturation (cis kinks), and shorter tails. Cholesterol is bidirectional — fluidizes below the transition temp, stiffens above it. Memorize
cis double bonds ↑ fluidity Cholesterol buffers fluidity (both ways) Phase-transition temperature Know
Membranes carry several lipid classes — phospholipids (which differ by head group), glycolipids, and cholesterol. Memorize
PC, PE, PS, sphingomyelin Cholesterol as a bilayer component Know
Types: transmembrane (α-helix or β-barrel), lipid-anchored, and peripheral. A single-pass TM segment is ~20 hydrophobic residues; hydropathy plots predict them. Memorize
β-barrel = porins GPI-anchor (non-cytosolic face) vs farnesyl/myristoyl/palmitoyl (cytosolic) Detergents solubilize membrane proteins Know
Singer–Nicolson model: proteins float in a fluid lipid sea. Lateral diffusion is fast; flip-flop is very slow and enzyme-dependent; mobility is restricted by the cortex, rafts, and junctions. Memorize
Lateral diffusion fast; flip-flop slow FRAP measures mobility Diffusion barriers (tight junctions, cortex) Know
Rafts are cholesterol- and sphingolipid-enriched microdomains that are more ordered and concentrate specific proteins. Memorize
Raft = cholesterol + sphingolipid Ordered nanodomain Platform for signaling Know
Carbohydrate sits only on the non-cytosolic (external) face — glycoproteins and glycolipids. Roles: protection, cell–cell recognition, adhesion. Sugars NEVER face the cytosol. Memorize
Glycocalyx external-only Lectins bind carbohydrate Sidedness is preserved through trafficking Know
Membranes are bent by proteins that scaffold or wedge into the bilayer, and by lipid composition. Memorize
Curvature-generating proteins (e.g., BAR domains) Lipid shape contributes to bending Ch. 11 · permeability, pumps, channels, membrane potential
Know
Small nonpolar molecules cross freely; small polar cross slowly; ions and large polar molecules need transporters. Memorize
Order: nonpolar > small polar > large polar > ions O₂/CO₂ free; ions strongly excluded Know
Channels are gated pores — fast, passive only, and don’t show classic saturation. Carriers bind and change conformation — can be active and saturate (Km). Memorize
Only carriers can pump (active) Carriers saturate (Km/Vmax); channels don’t Facilitated diffusion = passive carrier Know
Passive transport runs down the electrochemical gradient (chemical + electrical). For ions, equilibrium ≠ equal concentration — the membrane potential balances the concentration difference (Nernst). Memorize
Electrochemical gradient = concentration + charge Nernst equation Equilibrium can hold at unequal concentrations Know
Active transport moves solutes against their gradient using ATP or a coupled ion gradient. The Na⁺/K⁺ pump moves 3 Na⁺ out / 2 K⁺ in per ATP and is electrogenic. Memorize
Na⁺/K⁺-ATPase 3Na:2K P-type / V-type / ABC transporters Pump contributes <~10% directly to resting potential — K⁺ leak dominates Know
Symport = both solutes same direction; antiport = opposite. The driving ion is usually Na⁺ or H⁺. Flipping a symporter’s orientation does NOT convert it to an antiporter. Memorize
Symport vs antiport Na⁺–glucose symporter (SGLT) Coupling character is set by mechanism, not orientation Know
Ion channels are selective for particular ions and are gated — they open and close rather than staying permanently open. Memorize
Selective + gated Setting resting potential → §7 · firing action potentials → §8 Know
The potential comes from a tiny charge separation across the membrane capacitor. At rest, K⁺ leak channels dominate, so V sits near E_K; only a minuscule fraction of ions moves. Memorize
Resting ≈ −70 mV E_K ≈ −90 mV, E_Na ≈ +60 mV K⁺ leak dominant; pump <10% direct Know
Depolarization opens voltage-gated Na⁺ (rising phase → toward E_Na); inactivation + K⁺ opening repolarizes. Excitatory synapses depolarize (toward threshold); inhibitory hyperpolarize (away). Memorize
Voltage-gated Na⁺ (rise) / K⁺ (fall) Threshold · all-or-none · refractory period Ball-and-chain inactivation Know
Endocytosis (phago-, pino-, receptor-mediated) and exocytosis move bulk material; at steady state exo = endo (membrane balance). Memorize
Clathrin-coated pits · dynamin (scission) Receptor-mediated endocytosis (LDL) Exocytosis: vesicle fuses with plasma membrane Ch. 12 & 14 · organelles, mitochondria, chloroplasts, nucleus
Know
Organelles separate incompatible reactions, expand membrane surface area, and concentrate components. Memorize
Major organelles + their jobs Topological organization of the cell Know
Mitochondria first, chloroplasts second; both retain bacterial hallmarks. Evidence: double membrane, circular DNA, 70S ribosomes, binary fission. Memorize
Margulis 1967 70S (bacterial-type) ribosomes Order mito → chloroplast Know
Outer membrane (porins, permeable to small molecules), inner membrane (cristae, impermeable, holds the ETC + ATP synthase), and matrix (TCA cycle + mtDNA). Memorize
Outer / inner / IMS / matrix Cristae increase inner-membrane area TCA cycle in the matrix Know
The ETC pumps H⁺ into the IMS, building a proton-motive force that ATP synthase uses (chemiosmosis). Keep compartments straight: glycolysis in the CYTOSOL, TCA in the matrix, oxphos on the inner membrane. Memorize
Chemiosmosis (Mitchell) ATP synthase makes 3 ATP/turn; c-ring sets H⁺/ATP ~30 ATP and 6 O₂ per glucose Know
mtDNA is circular and maternally (cytoplasmically) inherited — non-Mendelian. It encodes only a few proteins; the rest are nuclear-encoded and imported. Memorize
16,569 bp, 13 proteins Maternal / non-Mendelian inheritance Heteroplasmy Know
A chloroplast has THREE membrane systems — outer envelope, inner envelope, and thylakoid — not two. Thylakoids house the light reactions; the stroma holds the dark reactions and cpDNA. Memorize
Three membranes (NOT two) Thylakoid / stroma / grana Own circular DNA Know
The nuclear envelope is a double membrane continuous with the ER; nuclear pores allow selective, bidirectional transport. The nuclear interior is topologically equivalent to the cytosol. Memorize
Nuclear pore complex (NPC) NLS · importin · Ran-GTP gradient · FG-repeats Envelope continuous with ER Know
Peroxisomes run oxidative reactions (fatty-acid β-oxidation; H₂O₂ handled by catalase) and occur in nearly all cells. Their proteins are imported post-translationally — while FOLDED. Memorize
Catalase / H₂O₂ PTS1 (C-terminal SKL) Import of folded proteins Know
The lumen of the ER/Golgi/lysosome is topologically equivalent to the cell exterior. Vesicle budding and fusion preserve sidedness — cytosolic faces stay cytosolic. Memorize
Luminal ≡ outside Sidedness conserved through trafficking Topological equivalence classes Ch. 12 & 13 · signals, ER/mito import, vesicles, targeting
Know
Three routes: nuclear pores (gated transport), transmembrane translocation (ER/mito/peroxisome), and vesicular transport. A protein with no signal stays in the cytosol (the default). Memorize
3 sorting mechanisms Signal sequence vs signal patch Default destination = cytosol Know
Each destination has its own signal; some are cleaved, some aren’t. Memorize
ER signal: N-terminal hydrophobic, cleaved Mito matrix: amphipathic N-terminal NLS: basic, not cleaved · PTS1: C-terminal SKL Know
Import is post-translational and requires the protein to be UNFOLDED (chaperone-held). It needs both the membrane potential and ATP (Hsp70 ratchet). Memorize
TOM (outer) / TIM (inner) Must be unfolded to thread the translocon Two signals cleaved in different compartments Know
Co-translational: SRP binds the emerging signal and PAUSES translation, then docks at the SRP receptor and hands the ribosome to the translocon (Sec61). The signal peptide is cleaved and stays in the translocon. Memorize
SRP + SRP receptor SRP binding pauses translation Sec61 translocon · signal peptidase Know
Start-transfer and stop-transfer signals set orientation; the number of TM segments (odd/even) fixes which side each terminus ends up. Memorize
Start-transfer / stop-transfer signals Signal-anchor sequences Cleaved N-signal → N-terminus in the ER lumen Know
N-linked glycosylation begins in the ER; chaperones check folding, and only correctly folded/assembled proteins exit. Persistent failures are retro-translocated and destroyed (ERAD). Memorize
N-linked glycosylation (on Asn) Calnexin / calreticulin ERAD · unfolded-protein response Know
Transport vesicles bud from one compartment and fuse with the next; a protein coat selects the cargo and shapes the budding vesicle. Memorize
Coated transport vesicles Coat selects cargo + drives budding Know
The Golgi is polarized cis→trans and progressively processes/matures glycosylation as proteins move through the stack. Memorize
cis / medial / trans / TGN Sequential processing across the stack Know
Lysosomal enzymes are tagged with mannose-6-phosphate in the Golgi and captured by the M6P receptor. Failure of M6P tagging causes I-cell disease. Secretion is constitutive or regulated. Memorize
Mannose-6-phosphate (M6P) + M6P receptor I-cell disease Constitutive vs regulated secretion Ch. 3 & 6 · lysosomes, autophagy, ubiquitin–proteasome
Know
Three systems: the lysosome (bulk, organelles, extracellular material), the proteasome (short-lived/misfolded cytosolic proteins, ubiquitin-tagged), and autophagy. Memorize
Lysosome vs proteasome vs autophagy Ubiquitin tag routes to the proteasome Know
A V-ATPase pumps H⁺ INTO the lumen to keep it at ~pH 5. Acid hydrolases work best at low pH — so a leak into the neutral cytosol does little damage (built-in safety). Memorize
V-ATPase pumps H⁺ IN Lumen ~pH 5 Acid hydrolases; low-pH safety mechanism Know
Lysosomes degrade material delivered by phagocytosis (engulfing particles) and by endocytosis; the vesicle fuses with a lysosome and acid hydrolases digest the contents. Memorize
Phagosome fuses with lysosome Acid hydrolases do the digestion Know
A missing hydrolase lets its substrate accumulate (e.g., Tay-Sachs, Gaucher). I-cell disease is a trafficking failure — enzymes are secreted instead of delivered (M6P tagging defect). Memorize
Tay-Sachs (hexosaminidase) I-cell disease (GlcNAc phosphotransferase / M6P) Substrate accumulation Know
Peroxisomes carry out β-oxidation and detoxify H₂O₂ via catalase; their proteins are imported while folded. Memorize
Catalase / H₂O₂ PTS1 (SKL) Import of folded proteins Know
The pathway targets short-lived, misfolded, and regulatory proteins; a K48-linked polyubiquitin chain is the degradation signal; the process is ATP-dependent. Memorize
Ubiquitin = 76 aa, ~96% conserved K48 polyUb = degrade; K63 = signaling ATP-dependent Know
The proteasome degrades ubiquitin-tagged proteins in an ATP-dependent way, chopping them into short peptides (not free amino acids). Memorize
ATP-dependent, ubiquitin-targeted Products are short peptides (NOT free amino acids) Know
Mono- vs poly-ubiquitin and the linkage type set the fate (K48 → degradation, K63 → signaling/trafficking). Ubiquitin is one of the most conserved proteins known. Memorize
~96% identity across 76 residues (~3 differ — NOT “one amino acid”) K48 vs K63 linkages The ubiquitin code Know
E1 activates ubiquitin (ATP), E2 conjugates it, and E3 ligase confers substrate specificity — hundreds of E3s give the system its selectivity. Memorize
E1 (activating) / E2 (conjugating) / E3 (ligase, specificity) ATP is consumed at E1 Degron = the recognition signal