lecture 3 biochemistry (week 1)

Question 1

what rate does water exchange H bonds?

Answer 1

10^11s-1

Question 2

what is the exchange of H bonds in water called?

Answer 2

flickering clusters

Question 3

what are the 5 classes of lipid?

Answer 3

fatty acids

glycerophospholipids

sphingolipids

glycerolipids

sterols

Question 4

what are the membrane lipids? what can these be classed as?

Answer 4

phospholipids

glycolipids

cholesterols

they can be classed as amphiphatic

Question 5

what do phospholipids form as a part of the hydrophobic effect?

Answer 5

they can spontaneously form vesicles

Question 6

what can cell membranes be described as?

Answer 6

asymmetric - this is important as it requires energy

Question 7

describe membrane lipids

Answer 7

the biosynthetic pathways are well understood and in some cases they are drug targets (statins)

the majority are synthesized in the ER

Question 8

what occurs at the interface between a water and a CH3 molecule?

Answer 8

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

Question 9

what does clustering non polar groups together do?

Answer 9

an increase of entropy, by minimising the area of contact between H2O and non polar hydrocarbons

Question 10

describe what phospholipases are, and describe what they do

Answer 10

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

Question 11

why is maintenance of lipid bilayer asymmetry?

Answer 11

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.

Question 12

describe the complexity of membrane

Answer 12

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

Question 13

how do lipids function?

Answer 13

lipids function as essential structural components of membranes

lipids function as signalling molecules.

lipids function as the chemical ‘identifiers’ of specific intracellular compartments

lipids also function as intracellular energy stores

Question 14

what do phospholipases do?

Answer 14

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

Question 15

phospholipase A2

Answer 15

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

Question 16

what do prostaglandins do?

Answer 16

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).

Question 17

what is the pathway of converting arachidonic acid into the products?

Answer 17

arachidonic acid –> prostaglandin H2 –> distal enzymes –> prostacyclin (in endothelium), prostaglandins (in kidney, mucosa, etc), thromboxane (in platelets)

Question 18

describe the action of prostaglandins

Answer 18

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

Question 19

describe thromboxane

Answer 19

a vasoconstrictor and a potent hypertensive agent

it facilitates platelet aggregation

in homeostatic balance in the circulatory system with prostacyclin; a related compound

Question 20

describe leukotrienes

Answer 20

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

Question 21

what do specific lipids do?

Answer 21

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)

Question 22

describe the endocannabinoid system

Answer 22

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

Question 23

describe endogenous cannabinoids

Answer 23

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

Question 24

describe cannabinoid receptors

Answer 24

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)

Question 25

functions of the ECS

Answer 25

complicated

linked to appetite, metabolism, pain, inflammation, sleep, motor control, and much more

rimonabant is an inverse agonist of CB1 receptor developed as an anti obesity drug

successfully caused weight loss but had a negative and dramatic effect on mood –> removed from the market on an emergency basis

Question 26

describe phosphoinositides

Answer 26

multiple forms of phosphorylated PIs exist

localised to distinct cellular compartments

bind specific sets of proteins that recognize the head groups

minor component of total lipidome but hugely important in many biological processes

species are inter related, and many of the key enzymes are known and well studied

coloured boxes represent key species with known biological effects, others becoming better understood