MP

Biochemistry Final Exam Review Notes

Exam Structure & Logistics

  • Final exam = cumulative in understanding but questions restricted to “new material”
    • Coverage window: irreversible enzyme inhibition (penicillin) → end of Chapter 13
    • Length & format: 8 pages, 105\text{ min}, mix of conceptual & memorization (heavier on rote recall than Exam 2)
    • Uploaded & “feature-locked”; accommodations already forwarded to SLDS
  • No mechanism-drawing or peptide/β-sheet sketching required, yet conceptual fluency with earlier material assumed
    • Eg. expect to reason about protonation states via Henderson–Hasselbalch but not to perform a full calculation
  • Instructor will not re-answer policy questions (refer to recording/email)
  • Common end-of-semester hurdle: fatigue → students under-perform despite exam predictability

Content Map – What the Instructor Explicitly Said WILL Appear

  • Glycolysis (10 rxns + regulation)
  • TCA / Citric Acid Cycle (8 rxns + regulation, incl. pyruvate dehydrogenase)
  • Gluconeogenesis (key bypasses & regulation)
  • Irreversible enzyme inhibition (penicillin exemplar)
  • Lipids & membranes
    • Drawing/identifying a generic phospholipid
    • Membrane transport (passive, channels, carriers, pumps)
  • Signal-transduction receptors
    • G-protein-coupled receptors (GPCRs)
    • Receptor tyrosine kinases (RTKs)
  • Regulation themes: glycolysis ⇄ gluconeogenesis, glycogen metabolism, allosteric vs covalent control

“Road-map is there – if you attended class you know every bullet.”

Foundational Concepts Still Tested Indirectly

  • Acid–base catalysis & serine protease types (recognition of covalent vs acid–base catalysis)
  • Henderson–Hasselbalch intuition
    \mathrm{pH}=\mathrm{pK_a}+\log\left(\frac{[\mathrm{A}^-]}{[\mathrm{HA}]}\right)
  • Amino-acid 1- & 3-letter codes, side-chain chemistries
  • Secondary-structure principles (α-helix, β-sheet) – conceptual, not artistic

Detailed Mechanistic Clarifications from Q&A

1 • Potassium Channel Selectivity (K^+ > Na^+)

  • Channel interior lined by backbone carbonyl oxygens → concentric “rings” of partial negatives
  • For ion passage each ring must simultaneously coordinate the cation
    • K^+ ionic radius is ideal – satisfies all \approx6 carbonyls per ring
    • Na^+ too small → can’t contact every carbonyl → channel does not fully open → low permeability
  • Any ion larger than K^+ is sterically excluded

2 • GPCR Activation Cycle

Ligand binds ▶ receptor conformational change ▶
αβγ trimer (GDP-bound) interacts ▶ α-subunit:
   • Releases GDP, binds GTP
   • Dissociates from βγ & receptor
Active α(GTP) + βγ each modulate effectors
  • Two mandatory events for activation:
    1. α-subunit dissociation
    2. GDP→GTP exchange
  • Switch-off mechanisms
    • Intrinsic α-GTPase hydrolyzes GTP → GDP → re-associates with βγ
    • \text{cAMP} degraded by phosphodiesterase ⇒ PKA regulatory/catalytic subunits re-assemble & shut down cascade

3 • PFK-2 / F-2,6-BPase “Bifunctional Enzyme” Toggle

  • Single polypeptide, two distinct active sites
    • Kinase domain (PFK-2) makes \text{F2,6BP}
    • Phosphatase domain (F-2,6-BPase) degrades \text{F2,6BP}
  • Phosphorylation state (via Protein Kinase A)
    • Unphosphorylated: PFK-2 active → ↑ F2,6BP → activates PFK-1 (glycolysis) & inhibits FBPase-1
    • Phosphorylated: Kinase off / phosphatase on → ↓ F2,6BP → glycolysis off, gluconeogenesis on
  • Tissue specificity: only gluconeogenic tissues (liver) express enzyme; muscle bypasses this layer (AMP alone regulates PFK-1)

4 • Glycogen Metabolism Regulation

  • Synthetic arm: \text{G6P} \to \text{G1P} \to \text{UDP–Glucose} → glycogen synthase adds to non-reducing ends
  • Degradative arm: glycogen phosphorylase (cleaves α-1→4) → G1P → G6P
  • Hormonal control
    • Glucagon / epinephrine (↑ cAMP → PKA): activate glycogen phosphorylase, inhibit glycogen synthase (breakdown predominates)
    • Insulin (↑ phosphatases): activate glycogen synthase, inhibit phosphorylase (synthesis predominates)
  • Allosteric cue: high [AMP] in muscle directly activates phosphorylase & PFK-1

5 • Cytosolic NADH Shuttles

  1. Malate–Aspartate Shuttle (liver & heart)
    • Cytosolic malate dehydrogenase: \text{OAA}+\text{NADH}+H^+ \to \text{Malate}+\text{NAD}^+
    • Malate transported → matrix; re-oxidized to OAA, regenerating mitochondrial \text{NADH} (\approx2.5\,ATP)
    • OAA ↔ aspartate transamination + aspartate transporter closes loop
  2. Glycerol 3-Phosphate Shuttle (muscle & most tissues)
    • Cytosol: DHAP + \text{NADH} → glycerol-3-P + \text{NAD}^+
    • Inner-membrane FAD-dependent G3P dehydrogenase: glycerol-3-P + FAD → DHAP + \text{FADH}2 → \text{Q} \to \text{QH}2 (feeds at Complex II level ⇒ ~1.5\,ATP/pair e^-)

6 • Membrane Lipid Diversity

  • Membranes ≠ pure glycerophospholipids
    • Sphingolipids: use sphingosine backbone (built-in long acyl tail, amide-linked second fatty acid, variable head group)
    • Glycolipids: carbohydrate head groups important for cell recognition & signaling; contribute to membrane asymmetry & microdomains

Study Strategy & Pitfalls

  • Begin with predictable list of pathways; practice recall (structures, enzymes, regulation logic)
  • Re-teach mechanisms aloud; if you can explain PFK-2 toggle or GPCR cycle without notes, you’re exam-ready
  • Manage burnout: schedule spaced sessions; leverage existing review videos
  • Write potential “why/what-if” regulation questions (e.g., “high [cAMP] in liver → glycolysis? gluconeogenesis?”) and answer them verbally

Equations & Values Worth Having Handy

  • Henderson–Hasselbalch (above)
  • Net ATP tallies (know where +2, +2.5, +1.5 come from in shuttles & ETC entry points)
  • Stoichiometries: \text{Glucose} \xrightarrow{\text{glycolysis}} 2\,\text{pyruvate} + 2\,\text{ATP (net)} + 2\,\text{NADH}_{\text{cyt}}

Ethical / Practical Implications Mentioned

  • None explicit; instructor emphasized academic integrity (ask questions publicly), mental well-being, and the transient nature of signaling (biological “switches” must both turn on & off)

Closing Remarks from Instructor

  • Office hours & 1-on-1s praised; students share common questions—don’t hesitate to post publicly
  • Semester wrap-up: stay rested; final success often correlates with simply persisting through exhaustion