Here are the notes for four of the nineteen topics of an upcoming examination.
Paracrine, endocrine, synaptic.
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
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)
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)
Necrosis: accidental cell death; swelling and lysis; results in inflammation
Apoptosis: programmed cell death; membrane blebbing, chromosome condensation, packaging into apoptotic bodies for phagocytosis
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
Cancer occurs when:
Refer to section Cell Signalling.
Self-sufficiency could develop due to any one of:
Ignoring cell checkpoints (continuing mitosis, etc.)
Ignoring typical inhibitions
resulting in chaotic growth.
Ineffectiveness of tumour-suppressor genes (e.g. p53)
Telomerase results in telomeres extending during mitosis; infinite replicative potential
Tumours secrete angiogenic factors, enabling angiogenesis (blood vessel formation)
This enables rapid tumour growth and later metastasis.
Cancer cells eventually circulate through bloodstream and form tumours elsewhere.
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.
Telomerase: present in germ cells (elongate telomeres during replication)
Immortal cells: after 10-20 cell doublings, telomerase is reactivated to maintain telomere length
Respiration: synthesis of ATP from glucose (and oxygen).
ATP: energy currency
NADH, FADH2: high-energy electron shuttles
Ten-step process; energy investment and payoff phases
Beginning with glucose:
From here on everything happens twice per glucose (once per G3P).
Census per glucose:
Occurs as pyruvate enters mitochondrion
Census per glucose:
Or citric acid cycle or whatever you call it, really.
Census per glucose:
Overall census so far:
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.
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.
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
Various molecules can undergo catabolism at different points
Phosphofructokinase (step 3) used to control respiration
…I don’t need to give an introduction, do I?
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)
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
The electron passed to Fd can be passed back to the cytochrome complex, forming a cycle.
Analogous to Krebs cycle
For 3 CO2: