Cell Biology

Here are the notes for four of the nineteen topics of an upcoming examination.


Cell signalling

The technicalities

Paracrine, endocrine, synaptic.

How does basically anything meaningful happen in a cell?

Reception

Signalling molecules bind to receptors.

G-protein coupled receptors: cell-surface transmembrane receptor which works with G-protein (GTP-binding)

Receptor tyrosine kinases: monomers with intracellular tails containing multiple tyrosines

Ligand-gated ion channels: membrane channel receptor containing a “gate”

Intracellular receptors: for hydrophobic or small signalling molecules which pass through cellular membrane

Transduction

Receptors undergo a conformational change and the signal is converted to a form eliciting cellular response, often via signal transduction pathways

Phosphorylation: phosphate groups added by protein kinases (phosphorylation cascade) and removed by protein phosphatases

Second messengers: small water-soluble non-protein molecules or ions which diffuse throughout cell (less expensive)

Response

just do your thing I guess

Signal amplification: an effect of cascades (every step)

Specificity and coordination: branching pathways, cross-talk, etc

Signalling efficiency: scaffolding proteins attach several relay proteins

Signal termination: binding reverses via several means (conversion of second messengers; phosphatases; G-protein hydrolysis)

Cell cycle and Cancer

Necrosis: accidental cell death; swelling and lysis; results in inflammation

Apoptosis: programmed cell death; membrane blebbing, chromosome condensation, packaging into apoptotic bodies for phagocytosis

Cell cycle

G1: pre-synthesis; S: DNA replication; G2: post-synthesis (prepare for mitosis)

Three important checkpoints: G1 (enter G0), G2 (abort mitosis), M (ensure kinetochore attachment before anaphase)

Cyclin-dependent kinases: a certain class of kinases which are activated by cyclin partner, always present

Cyclin: protein named for its cyclic expression changes, synthesised or degraded at various stages of cell cycle

Cyclin and CDK partnerships not exclusive

Six hallmarks

Cancer occurs when:

1. cells want to live (self-sufficiency in growth signals)

Refer to section Cell Signalling.

Self-sufficiency could develop due to any one of:

2. cells don’t want to die (insensitivity to anti-growth signals)

Ignoring cell checkpoints (continuing mitosis, etc.)

Ignoring typical inhibitions

resulting in chaotic growth.

3. killing them doesn’t kill them (apoptosis evasion)

Ineffectiveness of tumour-suppressor genes (e.g. p53)

4. time doesn’t kill them (replicative potential; telomerase)

Telomerase results in telomeres extending during mitosis; infinite replicative potential

5. food doesn’t kill them (angiogenesis)

Tumours secrete angiogenic factors, enabling angiogenesis (blood vessel formation)

This enables rapid tumour growth and later metastasis.

6. space doesn’t kill them (metastasis)

Cancer cells eventually circulate through bloodstream and form tumours elsewhere.

Multistep progression model

1. Mutations

Tumour-suppressor genes (preventing abnormal cell growth) inactivated / absent.

Example: p53 “guardian of genome”

Inactive form: p53-mdm2 complex

Upon DNA damage or cell cycle abnormalities: p53 is activated and results in:

  • Cell cycle arrest, DNA repair, cell cycle restart
  • Apoptosis, elimination of damaged cell

Recessive loss-of-function mutations: with two mutated genes no normal protein is expressed.

Proto-oncogenes (encouraging cell proliferation etc.) mutate into oncogenes.

This results in overproduction of growth factors; mutant receptors; mutant relay proteins; mutant transcription factors.

Example: Ras (G-protein)

A hyperactive Ras protein issues signals regardless of receptor conformation, resulting in protein overexpression and increased cell division.

2. Activation of telomerase

Telomerase: present in germ cells (elongate telomeres during replication)

Immortal cells: after 10-20 cell doublings, telomerase is reactivated to maintain telomere length

3. Angiogenesis

4. Metastasis

respiration

Okay.

Respiration: synthesis of ATP from glucose (and oxygen).

ATP: energy currency

NADH, FADH2: high-energy electron shuttles

1. Glycolysis: oxidising glucose into pyruvate

Ten-step process; energy investment and payoff phases

Beginning with glucose:

  1. Add 6-phosphate (-ATP)
  2. Convert glucose to fructose
  3. Add 1-phosphate (-ATP)
  4. Cleave into G3P and DHAP
  5. G3P DHAP (never reaches equilibrium, G3P used)

From here on everything happens twice per glucose (once per G3P).

  1. G3P oxidised and 1-phosphate added (+NADH)
  2. Phosphorylation (+ATP)
  3. Relocate 3-P to 2-P
  4. H2O removed to form PEP
  5. Phosphorylation (+ATP) to form pyruvate

Census per glucose:

Occurs as pyruvate enters mitochondrion

Census per glucose:

2. Krebs cycle

Or citric acid cycle or whatever you call it, really.

Census per glucose:

Overall census so far:

3. Oxidative phosphorylation

Electron transport chain

Electrons are passed along membrane proteins with increasing electronegativity.

NADH: I → Q → III → Cytochrome C → IV → O2 (forming H2O)

FADH2: II → Q → III → Cytochrome C → IV → O2 (forming H2O)

I, III, IV are transmembrane proton pumps which pump protons out of the mitochondrion.

II is not; FADH2 is slightly less efficient.

Chemiosmosis

H+ gradient across mitochondrial membrane: protons diffuse back in across ATP synthase due to proton-motive force, forming ATP.

ATP: 4 ATPNADH: 2.5(10)=25 ATPFADH2: 1.5(2)=3 Possible -2

Total: 4 + 25 + 3 − (0 or 2) = 30 or 32 ATP.

Anaerobic respiration

Glycolysis still occurs as usual.

For anaerobic respiration: the electron transport chain still occurs (but not ending in O2).

Alternatively fermentation occurs outside the mitochondrion.

Obligate anaerobes/aerobes; facultative anaerobes

Versatility

Various molecules can undergo catabolism at different points

Regulation

Phosphofructokinase (step 3) used to control respiration

Photosynthesis

…I don’t need to give an introduction, do I?

Chloroplasts

These comprise stroma (fluid), and grana (singular: granum) with folds known as thylakoids.

Chlorophyll comprises a light-absorbing porphyrin ring and hydrocarbon tail.

Chlorophyll α: key light-capturing pigment, participates directly in reactions

Chlorophyll β: accessory pigment (transfers energy to other pigments)

Carotenoids (carotene, xanthophylls): accessory pigments (prevent overexposure; broaden absorption spectra)

1. Light reaction

Photosystem: collection of light-harvesting complexes around a reaction-centre complex in a thylakoid membrane

Photosystem II: reaction-centre chlorophyll α: P680 (absorbs 680nm best)

Photosystem I: reaction-centre chlorophyll α: P700

Process:

Cyclic electron flow

The electron passed to Fd can be passed back to the cytochrome complex, forming a cycle.

2. Dark reaction (Calvin cycle)

Analogous to Krebs cycle

For 3 CO2:

  1. Carbon fixation
    • 3 RuBP + 3 CO2 → 6 3-phosphoglycerate
    • Add 1-phosphate (-6 ATP)
  2. Reduction
    • Reduced (by NADPH) to form 6 G3P (1 G3P output)
  3. Regeneration
    • 5 G3P to 3 RuBP (-3ATP)