Bio chem Chat review

Factors that INCREASE fluidity

More unsaturated fatty acids, Shorter fatty acid chains, Higher temperature

Factors that DECREASE fluidity

More saturated fatty acids, Longer fatty acid chains, Lower temperature

Cholesterol in the membrane

Stabilizes membrane fluidity, Prevents membranes from becoming too rigid or too fluid

Liquid Ordered (Lo)

More tightly packed, More cholesterol, longer saturated fatty acid chains, low temperatures

Liquid Disordered (Ld)

More fluid, More unsaturated fatty acids, Higher temperature

Triacylglycerol

Energy storage, Cannot form bilayers

Phospholipids

Amphipathic, Form bilayers

Sphingomyelin

Common in myelin, Found in lipid rafts

Cholesterol

Membrane fluidity buffer, Present in lipid rafts

Arachidonic acid

Precursor to inflammatory signaling molecules

Phospholipases

PLA1, PLA2, C, D

PLA1

Cuts fatty acid at carbon 1

PLA2

Cuts fatty acid at carbon 2, Often releases arachidonic acid

PLC

Cuts before phosphate group, Produces DAG + phosphorylated head group

PLD

Cuts after phosphate group, Produces phosphatidic acid

Channels

Very fast, Usually not saturable in same way as enzymes, Allow diffusion down gradient

Transporters

Slower, Saturable kinetics, Often undergo conformational changes

P-type ATPases

Become phosphorylated during transport cycle, Example: SERCA

SERCA Mechanism

photo

F-type ATPase

Produces ATP using proton gradient

V-type ATPase

Acidifies intracellular compartments

ABC transporter

ATP-powered transporter, Multidrug resistance

Aquaporin

Water transport

SNARE proteins

facilitate membrane fusion

Caveolin

Caveolae formation

Transmembrane α-helices are rich in

Ile, Val, Leu, Phe

Charged residues are unfavorable in membrane core

Lys, Arg, Asp, Glu

Free Energy Transport Equation

ΔG = RT ln(C2/C1) + zFΔΨ

Key idea of ΔG

Negative ΔG = favorable, Positive ΔG = unfavorable

RTK Key sequence

RTK → IRS-1 gets P → P-IRS-1 binds to Grb2 → Grb2 binds to Sos → Sos bind to Ras → Ras stimulate GDP/GTP exchange →Ras binds to Raf → Raf p-lates MEK → MEK p-lates ERK

Ras

small GTPase

Sos

GEF

Raf

MAPKKK

MEK

MAPKK

ERK

MAPK

Amplification (Signal Transduction)

One signal activates many downstream molecules

Modularity (Signal Transduction)

Scaffold proteins organize pathways

Divergence (Signal Transduction)

One signal activates multiple outputs

Integration (Signal Transduction)

Multiple pathways combine signals

Localized response (Signal Transduction)

Signal confined to specific region

Steps of cell division

G1 → S → G2 → M → G0

G1 (cell division)

cell making RNA and proteins

S (cell division)

DNA synthesis

G2 (cell division)

RNA and protein synthesis

M (cell division)

Nucleus and cell division

G0 (cell division)

terminally differentiated cells

Cyclins

Levels fluctuate, Synthesized and degraded each cell cycle

CDKs

Kinases activated by cyclins

CDK activation Requires

cyclin binding, activating phosphorylation, removal of inhibitory phosphate

Apoptosis Characteristics

Programmed cell death, Caspase activation, DNA fragmentation, Cell shrinkage, Minimal inflammation, can occur during development

Apoptosis can be triggered by

DNA damage, developmental signals, death receptor signaling

Oncogenes

Gain-of-function mutations, Promote cell division

Examples of oncogenes

Ras, erbB2

Tumor suppressors

Loss-of-function mutations, Normally inhibit cell division

Examples of tumor suppressors

p53, Rb, BRCA1

SERCA

P-type ATPase, pumps Ca2+ from cytosol to ER lumen

Lipid rafts

cholesterol + sphingolipids

Unsaturated FA

increase fluidity

Saturated FA

decrease fluidity

Caspases

drive apoptosis

tracrRNA

naturally occurring bacterial immune locus (RNA involved in guide RNA processing)

Cas9

DNA cutting enzyme (breaks double bonds)

PAM

recognized DNA sequence adjacent to target DNA

Homology-directed repair

precise DNA repair mechanism

non-homologous end joining

error prone repair mechanism

sgRNA

synthetic RNA combining two RNA components

Aquaporins

channel proteins that facilitate the passage of water

flippase

requires ATP to transport lipids from one leaflet to another

scramblase

randomized phospholipid distribution across leaflets

caveolin

important in caveolae formation

t-snare

facilitates membrane fusion

voltage-gated channel

open and close in response to changes in membrane potential

ligand-gated channel

binding of ligand causes allosteric transition that opens and closes channel

1 mM

10^-3 M

eicosanoids

lipid derived signaling molecule involved in inflammation

cholesterol

sterol abundant in mammalian plasma membranes

SERCA Pathway

ATP binds to Ca2+ → Asp is P-lated → Ca2+ released into lumen → ADP is released → deP-lation of p domain →original domain conformation is reset

B-adrenergic receptor desensitization pathway

cAMP activate PKA → PKA P-lates BARK → BARK binds to GbGy receptor → receptor is p-lated → Barr binds to receptor → GbGy released → Barr receptor complex is endocytosed (turned off)

cAMP activates

PKA

RTK has

intrinsic tyrosine kinase activity

MAP kinase cascade

signaling pathway that uses RTK, IRS-1, Grb2, Sos, Ras, Raf, MEK, ERK

cyclin

protein synthesized during every cell cycle

ubiquitinated cyclin

tags proteins for degradation

phosphotase

removes inhibitory phosphate from CDK

destruction box recognition protein

triggers cyclin ubiquitination

CDK

cyclin dependent kinase

mutant RTK active even without ligand binding...

promotes cell division, oncogene

loss of p53 =

increase cancer risk

erbB2

oncogene

crRNA

RNA containing sequence complementary to target DNA

phosphatidylcholine

2 fatty acid chains + phosphate, CH2, CH2, N+, 3CH3

phosphatidylethanolamine

2 fatty acid chains + phosphate, CH2, CH2, NH3+

phosphatidic acid

2 fatty acid chains + phosphate, H

phosphatidylserine

2 fatty acid chains + phosphate, CH2, C, NH3+, COO-, H

Phosphatidylinositol 4,5-bisphosphate

2 fatty acid chains + phosphate, 6 carbon ring, -OH on C 2 3 and 6, OP on C 4 and 5

floppase

moves phospholipids from cytosol to outer leaflet

sphingomyelin

membrane lipid abundant in myelin

lipid derived signal molecules involved in inflammation

prostaglandins, leukotrienes, thromboxanes

lipids that can form bilayers

phospholipids and sphingolipids

signaling pathway that activates Akt

PI3K