lecture 3 biochemistry (week 1) Flashcards
what rate does water exchange H bonds?
10^11s-1
what is the exchange of H bonds in water called?
flickering clusters
what are the 5 classes of lipid?
fatty acids
glycerophospholipids
sphingolipids
glycerolipids
sterols
what are the membrane lipids? what can these be classed as?
phospholipids
glycolipids
cholesterols
they can be classed as amphiphatic
what do phospholipids form as a part of the hydrophobic effect?
they can spontaneously form vesicles
what can cell membranes be described as?
asymmetric - this is important as it requires energy
describe membrane lipids
the biosynthetic pathways are well understood and in some cases they are drug targets (statins)
the majority are synthesized in the ER
what occurs at the interface between a water and a CH3 molecule?
water molecules have fewer opportunities or H bond exchange (forces are anisotropic) leading to longer than usual lifetime of H bonds, an ice like structure at the interface and a decrease in entropy. thus water at the interface is rotationally and translationally constrained
what does clustering non polar groups together do?
an increase of entropy, by minimising the area of contact between H2O and non polar hydrocarbons
describe what phospholipases are, and describe what they do
cleave glycerophospholipids to generate lipids
act as second messengers
they are a ubiquitous group
diverse in site of hydrolysis
they are of pharmacological interest as they have a role in inflammation
why is maintenance of lipid bilayer asymmetry?
phosphatidylinositol is a key signalling molecules is on the inside of the plasma membrane
during apoptosis a phosphatidylserine specific flippase is activated, revealing this lipid on the surface of the dying cell. This is recognised by macrophages which then consume the corpse
blood platelets sequester phosphatidylserine (PS) in the cytoplasmic leaflet of their plasma membrane, but when activated in response to blood vessel injury, they scramble the lipids in the two leaflets of the membrane to expose PS at the cell surface where it functions as an essential cofactor in the conversion of coagulation proteins into a blood clot
can influence protein targeting, sorting and function (4H material)
there is also asymmetry in the different membrane compartments.
describe the complexity of membrane
it has been estimated eukaryotic cells contain many thousands of different lipid species, based upon different head groups, different fatty acyl chain lengths and saturations
originally thought that this reflected the rather non-specific nature of lipid bilayers (heterogeneous mixtures but fluid platform is ‘all’ that is required for membrane function
how do lipids function?
structural components of membranes
lipids function as signalling molecules.
chemical ‘identifiers’ of specific intracellular compartments
intracellular energy stores
what do phospholipases do?
a phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances by hydrolysis
when membrane lipids are hydrolysed they are removed from the membrane and therefore the structure and integrity and fluidity of the membrane may be altered
in some cases, a chemical moiety derived from the lipid is released from the membrane and acts as a signalling molecule
usually cytosolic proteins
phospholipase A2
PLA2 has a major role in signal transduction as it releases arachidonic acid which serves as a precursor for the biosynthesis of :
prostaglandins
thromboxane
leukotrienes
what do prostaglandins do?
prostaglandins exert only a paracrine (locally active) or autocrine (acting on the same cell from which it is synthesised) function.
they are potent but have a short half-life before being inactivated and excreted.
there are currently nine known prostaglandin receptors on various cell types.
prostaglandins act on a subfamily of cell surface seven-transmembrane receptors, G-protein-coupled receptors (GPCRs).
what is the pathway of converting arachidonic acid into the products?
arachidonic acid –> prostaglandin H2 –> distal enzymes –> prostacyclin (in endothelium), prostaglandins (in kidney, mucosa, etc), thromboxane (in platelets)
describe the action of prostaglandins
dilatation in vascular smooth muscle cells (lower blood pressure)
platelet aggregation
sensitise spinal neurons to pain
constrict smooth muscle (eg uterine contraction RU486/mifepristone)
regulate inflammatory processes
regulate calcium movement
describe thromboxane
a vasoconstrictor and a potent hypertensive agent
it facilitates platelet aggregation
in homeostatic balance in the circulatory system with prostacyclin; a related compound
describe leukotrienes
stimulate proinflammatory activities such as endothelial cell adherence and chemokine production by mast cells
as well as mediating inflammation, they induce asthma and other inflammatory disorders, reducing the airflow to the alveoli
what do specific lipids do?
they exert specific effects with clearly biological consequences
these that tell us that individual lipids, although often very minor components of cell membranes are there for a reason
an example - phosphatidylinositol 4,5-biphosphate (PIP2)
describe the endocannabinoid system
important modulatory system
comprised of cannabinoid receptors, endogenous, cannabinoids(endocannabinoids) and the enzymes responsible for the synthesis and degradation of the endocannabinoids
disruptions in the ECS is linked to schizophrenia and many other conditions
describe endogenous cannabinoids
2-arachidonoyl glycerol (2-AG)
arachidonoyl ethanolamide (anandamide)
have different physiological and pathophysiological roles
synthesized from omega 6 polyunsaturated fatty acids
despite AEA and 2-AG both containing arachidonic acid, their routes of synthesis and degradation in vivo are almost completely distinct and are mediated by different enzymes
describe cannabinoid receptors
CB! and CB2 receptors are both GPCR
principally couple to GI and Go classes
CB1 receptors are abundant in the CNS
CB2 is expressed in the PNS and in immune cells
other receptors - transient receptor potential (TRP) channels
peroxisome proliferator activated receptors (PPARs)
