Week 2 Flashcards
(57 cards)
Major lipids of the plasma membrane
1) PE
2) PS
3) PI
4) PC
5) SM
6) Cholesterol
7) Glycolipids
1) Phosphatidyl ethanolamine- inner leaflet, neutral
2) Phosphatidyl serine- net negative charge, inner leaflet
3) Phosphatidyl Inositol- net negative charge, inner leaflet, can be phosphorylated in cell signaling
4) Phosphatidyl Choline- Neutral, outer leaflet
5) SPhingomyelin-outer leaflet, non-glycerol back bone
6) rigid planar structure that fits between kinks in phospholipid. Adds stiffness to membrane and lowers permeability
7) component of outer membrane, heavily involved in cell recognition and signaling. (ABO antigens)
Proteoglycans
Separate class of glycolipids that have longer unbranched glycosylation. Important in ECM formation, glycocaalyx formation and cell-cel signaling/recognition.
What is the site of the cytochrome p450 enzymes?
What is the main function of them?
Membrane proteins found in the SER membrane in the liver.
Detoxify many drugs and toxins, particularly lipid soluble ones in two phases.
First phase is oxidation, reduction, or hydrolysis.
Second phase tags the molecule with a polar group to make it water soluble and excretable through kidneys.
What affect does acetylcholine have on the following cells?
Skeletal muscle, cardiac muscle, salivary glands.
Contraction of skeletal muscle
Secretion from salivary glands
Decreased contractility in cardiac muscle
Myasthenia Gravis
Cause, symptoms, and treatment
Autoimmune disorder that creates antibodies for acetylcholine receptors on skeletal muscle.
Fatigue, weakness, droopy mouth, and single droopy eyelid, double vision, unsteady walking, difficulty swallowing
Steroids to inhibit immune system, acetylcholinesterase inhibitor to up Ach in synapse.
G-proteins Gs Gi Gq
Gs=stimulates Adenylyl cyclase
Gi= inhibits adenylyl cyclase
Gq activates phospholipase C
What is the most numerous type of enzyme linked receptors, how does it work, and what processes is it typically involved in?
Tyrosine kinases, dimerized upon ligand (growth factor) binding with cross phosphorylation. Phosphorylated intracellular domains activate other proteins.
Typically involved in growth, survival
Ion channel linked receptors are typically found where?
Receptors in synapse on neuron dendrites
How does NO result in vasodilation?
Made by NO synthase from, diffuses easily across membranes where it binds and activates guanylyl cyclase to upregulate cGMP production to then signal relaxation of smooth muscle.
Good for angina, and high BP.
Very powerful and unstable. Short lived paracrine
What two hormones activate the cAMP/PKA system?
Epinephrine and norepinephrine both bind GPCRs to activate cAMP system.
Explain the PI phospholipase C pathway.
Phospholipase C breaks down phosphorylated PI (PIP2) to then form IP3 and DAG. IP3 goes in to trigger Ca2+ release from ER. DAG and Ca2+ then activate protein kinase C.
RAS
Monomeric G-protein activated by nearly all tyrosine kinase receptors.
Activate RAS-MAPK cascade (3 successive kinases that result in altered gene expression and protein activity)
RAS mutations are present in 30% of all cancers (oncogene, typically stimulate overactive cell proliferation)
PI-3 Kinase pathway
PI is phosphorylated at position 3 to make PI3P.
PI3P stays attached to lipid membrane. Stimulates cell growth and survival
This pathway is stimulated by RAS as well
JAK STAT pathway
Short pathway important in immunity and inflammation.
No intrinsic tyrosine kinase
Receptor is phosphorylated by JAK after binding cytokines(protein signals), attracts and activates STAT proteins that go on to nucleus to affect gene expression.
JAK inhibitors used to treat arthritis and othe inflammatory diseases
TGF-Beta Pathway
Short pathway involved in development.
Receptor is a serine threonine kinase.
Ligand binding leads to phosphorylation TGF-beta receptors. SMADS is then activated which travels to nucleus to affect expression of genes.
Desensitization
COnstant activation of receptors leads to decreased activation of proteins.
Best studied in GPCRs where GPCR kinases can come in to cause arrestin to bind to GPCR and blockchain activity.
Other mechanisms are down regulation of receptor synth, increased receptor turnover, endocytosis of receptor.
Beta adrenergic receptors
Bind epi and norepi to regulate contractility in heart. Associate Gs to stimulate cAMP pathway.
Damage to heart can cause activation of sympathetic nervous system leading to constant epi/norepi levels leading to desensitization of GPCR receptors. Vicious cycle.
Ironically beta blockers can ease this problem.
INsulin receptor
Pre-dimerized tyrosine kinase receptor. Activates MAPK and PI-3K pathways for cell growth/proliferation. and upregulation of insulin receptors
AKT
Downstream in PI-3K pathway. Has many effects. Don’t know why we have to know this.
Name the proteins and steps involved in vesicle formation
Cargo receptors bind adaptin and then clathrin protein molecules as invagination occurs. Dynamin pinches off the vesicle and then the clathrin and adaptin fall off to be recycled to the membrane.
Enzyme and amino acid residue typically associated with glycosylation
Asn, oligosaccharyl transverse
How are acid hydrolases tagged for transport to lysosomes?
Diseases associated with this?
Acid hydrolases are tagged with a mannose 6 phosphate that docks them into a receptor in the Golgi apparatus that then buds off. Resulting vesicles go on to fuse with an early endosome.
Lysosomal storage diseases typically result in death before 15 years. Child is born normal but accumulation of substrates results in cell death.
Inclusion cell disease= mannose is never phosphorylated and hydrolases are not properly marked for transport to endosome. Excreted from cell.
Familial Hypercholesteremia
Mutations in LDL receptor result in excessive cholesterol levels in blood.
Systemic deposits and atherosclerosis result
Inert binding site
Endogenous binding site of a drug that does not result in any relevant chemical response.
Blood albumin is a common site of this.
