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BMB > Control of Metabolism > Flashcards

Control of Metabolism Flashcards

1
Q

how is the atp pool buffered during intense exercise

A

by PCr

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2
Q

powering muscle contraction with glucose

A
  • ATP from glycolysis
  • intense exercise - PCr buffers ATP pool (though PCr is limited so must also mobilise glycogen
  • anaerobic metabolism producing lactate - possible for short periods only
  • prolonged exercise - aerobic metabolism of glucose, producing ATP more slowly, by OXPHOS
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3
Q

liver and blood glucose

A
  • after a meal - insulin stimulates uptake of glucose, which is converted to glycogen, FAs, used as fuel
  • after a fast - glucagon stimulates glycogenolysis, glucose release, mobilisation of FAs from adipose
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4
Q

3 key control points of glycolysis

A

hexokinase, PFK1, pyruvate kinase - irreversible steps with larger changes in gibbs free energy

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5
Q

what happens to lactate and alanine from anaerobic metabolism in muscle

A

released into blood and converted into glucose in the liver - glucose then released into blood and transported to muscle
= the cori cycle

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6
Q

6 ways to control enzyme activity

A
  • substrate level control
  • cooperativity
  • allosteric regulation
  • covalent modification
  • substrate cycling
  • control through changes in enzyme concentration
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7
Q

substrate level control

when most useful?

A
  • enzyme has greatest sensitivity to changes in [S] when [S}
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8
Q

example of substrate level control

A

glucokinase - an isoform of hexokinase with a high Km for glucose

  • B cell - glucokinase is glucose sensor, increase glycolytic flux and insulin release
  • liver - glucose uptake
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9
Q

cooperativity definition

A

binding of first substrate affects binding of subsequent

increases sensitivity

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10
Q

concerted model of cooperativity

A

binding of first substrate shifts equilibrium in favour of relaxed form which has higher affinity for further substrate

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11
Q

sequential model of cooperativity

A

binding of first substrate causes conformational change from T to R (higher aff), this causes second subunit to change from T to R, facilitates binding of 2nd substrate

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12
Q

hill coefficient

protein p with n binding sites for ligand L

A

n=hill coefficient, a measure of cooperativity (< no binding sites)

(read eqn)

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13
Q

allosteric effectors

A

bind to a site on the enzyme other than the substrate binding site and regulate enzyme activity

eg activator could produce a conformational change to stabilise the R state

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14
Q

allosteric effectors in muscle glycolysis

A
  • G6P allosterically inhibits muscle hexokinase
  • PFK1 allosterically inhibited by ATP and activated by AMP
  • PK allosterically activated by F16BP
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15
Q

sensitivity of … substrate level control, cooperativity, allostery

A

substrate level = linear response

others are more sensitive, sigmoidal rather than hyperbolic response curves

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16
Q

substrate cycling example

A

F6P, F16BP, via PFK1 and F16BPase
AMP allosterically activates PFK and inhibits F16BPase, allowing massive changes in flux with small changes in AMP levels/ the enzyme activities
- payed for by ATP, energy released as heat

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17
Q

types of covalent modification

A

phosphorylation

acetylation

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18
Q

shape of curve with cooperativity

A

sigmoidal

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19
Q

example of cooperativity in a monomeric enzyme

A

glucokinase = monomeric with 1 glucose binding site. has 2 slowly interconverting forms
- at low S, the low affinity E’ form dominates
- at high S, the high affinity E form dominates
this gives a sigmoidal saturation curve

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20
Q

AMP changes during exercise and allostery

A
  • large increase in AMP during exercise as 2ADP==>ATP+AMP by adenylate kinase
  • PFK1 activated by AMP, increases F16BP steady state
  • increases allosteric act of PK
  • decrease in steady state G6P, less inhibition of hexokinase

so a coordinated increase in activities of these enzymes

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21
Q

protein phosphorylation

A
  • at OH groups of ser, thy, tyr
  • introduces neg charge so can cause large conformational change
  • by kinases, removed by phosphatases
    these enzymes are promiscuous - have many targets. also many regulatory subunits
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22
Q

enzymes of glycogen metabolism

A

glycogen synthase converts UDPG to glycogen

phosphorylase converts glycogen to G1P, which is in equilibrium with G6P

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23
Q

how is gluconeogenesis like the reverse of glycolysis?

A

most of the reactions are at equilibrium so readily reversible for gluconeogenesis
- the HK, PFK1 and PK reactions are not (these ones use ATP) so different enzymes are required for the reversal:
F16BPase and pyruvate carboxylase+phosphoenolpyruvate carboxykinase

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24
Q

glycogen synthase and phosphorylase activities

A

don’t want simultaneous activity as will just turn over ATP

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25
Q

Phosphorylase

A
  • AMP or phosphorylation converts to more active form (R form - allo, phosphorylase b->a - covalent)
  • negative phosphate interacts with positive arginines, causing a large conformational change of a helices. exposes more + args of active site which are able to bind the negative phosphate of the substrate
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26
Q

lysine acetylation

A

almost every metabolic enzyme of the cell is acetylated - widespread importance in control

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27
Q

T,R, b,a forms of enzyme

A

T/R to do with allosteric regulation

a/b to do with activation by phosphorylation

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28
Q

adrenaline cascade and action on phosphorylase and glycogen synthase

A
  • adrenaline activated adenylate cyclase
  • cAMP
  • cAMP activates PKA
  • PKA activates phosphorylase kinase and inactivates glycogen synthase (-> b form)
  • phosphorylase kinase phosphorylases and activates phosphorylase (-> a form)
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29
Q

phosphorylase kinase

A
  • activated by phosphorylation by PKA

- activates phosphorylase and inactivates glycogen synthase by phosphorylation

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30
Q

protein phosphatase 1

A

reverses phosphorylation of phosphorylase, glycogen synthase, to decrease the rate of glycogen breakdown. GS and P are within the glycogen particle

  • PP1 doesn’t have affinity for the glycogen particle until it associates with a G subunit
  • PKA phosphorylates the G subunit, inactivating it (ensuring proteins remain phosphorylated, by turning off the dephosphorylation)
  • phosphorylation of the inhibitor of PP1 activates the inhibitor, so inhibits the phosphatase
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31
Q

glycogen synthase and phosphorylase activation states

A

GS=active when dephosphorylated

phosphorylase is inactive when dephosphorylated

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32
Q

insulin and glycogen synthesis

A
  • insulin activates insulin sensitive kinase and PP1
  • dephosphorylate glycogen synthase - activating
  • dephosphorylate phosphorylase kinase - inactivating
    phosphorylate G subunit of PP1 at a different site, activating the phosphatase to enter glycogen particles
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33
Q

allosteric regulation of liver phosphorylase

how does it differ from regulation of muscle phosphorylase

A
  • no large variation in AMP so AMP doesn’t activate the b form
  • level of a form is regulated by glucose binding
  • phosphorylase a is a glucose sensor in the liver, binding of glucose to phosphorylase converts it to an inactive T form, promotes dephosphorylation by PP1 (inhibit further production of glucose by liver glycogenolysis when BGC is high)
  • also activate glycogen synthesis as phosphorylase a->b leads to PP1 release, which binds tightly to a form, PP1 can then activate glycogen synthase

((there is much more phosphorylase than PP1 so most phosphorylase has to be converted to the bform to release sufficient PP1 to increase glycogen synthase activity))

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34
Q

AMP dependent protein kinase

A

allosteric activation by AMP. phosphorylation of AMPK by and upstream kinase is needed for this.
AMPK limits further utilisation of ATP by inhibiting glycogen, FA and cholesterol synthesis.

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35
Q

advantages of protein phosphorylation for metabolic control

A
  • signal ampl as enzymes have multiple targets
  • coordination between regulatory networks
  • increase sensitivity - small change in initial signal causes large change in end product (small change in relative kinase and phosphatase Vmaxes causes larger change in proportion of phosphorylated substrate with enzymes close to saturation (‘switch’ - more binary response) … is enzymes not near saturation, decrease in protein conc decreases kinase activity, slower change
  • regulation of kinase and phosphatase in opposite directions gives greater sensitivity
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36
Q

purpose of PP1

A

removes all the phosphates involved in the regulation of glycogen metabolism, decreases rate of glycogen breakdown and accelerates glycogen synthesis

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37
Q

AMP

A

a sensitive indicator of cellular energy levels via the adenylate kinase equilibrium

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38
Q

what enhances adenylate cyclase activity in the liver

A

glucagon
B-adrenergic agonists

increases cAMP, activate PKA amd phosphorylate 6PF2K/F26BPase

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39
Q

what is 6PF2K/F26BPase?

A

a bifunctional enzyme found in the liver which is phosphorylated by PKA, this inhibits the kinase activity and stimulates the phosphatase activity so get more F6P and less F26BP

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40
Q

F26BP and liver glycolysis/ gluconeogenesis

A

allosteric activator of PFK1 and inhibitor of F16BPase

causes enhanced glycolysis and inhibition of gluconeogenesis

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41
Q

pyruvate kinase - allostery

covalent mod

A

inhibited by ATP and alanine, activiated by F16BP (feedforward)

inhibited by phosphorylation prior to saturation

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42
Q

Ca2+ linked hormones and gluconeogenesis

A

Ca2+-CaM dependent protein kinase phosphorylates pyruvate kinase, inhibiting it.
so promoting gluconeogenesis

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43
Q

why does elevated cAMP activate glycolysis in muscle but inhibit glycolysis in liver?

A

in the liver, 6PF2K/F26BPase and PK are phosphorylated and inhibited, whereas the musce isoforms lack a PKA phosphorylation site

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44
Q

PEPCK acetylation

A

enhanced by high glucose, decreased by high amino acid. promotes degradation of the protein

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45
Q

regulation of glucokinase by a regulatory protein

A

not inhibited by G6P but is inhibited by a regulatory protein. F6P binds the regulatory protein and reinforces the inhibition
the inhibition is antagonised by F1P - ensures liver takes up both glucose and fructose following a meal.(?)

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46
Q

glucose transport

A 
GLUT1,3 = present in all cells, low Km
GLUT2 = liver, pancreatic B cells, high Km so uptake dep on BGC
GLUT4 = muscle, adipose, recruited to plasma membrane by insulin
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47
Q

control through changes in enzyme concentration

A

longer term, change gene expression

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48
Q

control through changes in enzyme concentration - liver glycolysis and gluconeogenesis

A

insulin - stimulates expr of PFK1, PK, 6PF2K/F26BPase

glucagon - inhibits expression of these enzymes and stimulates expression of PEPCK and F16BPase

49
Q

CRE

A

cAMP response element

palindromic DNA sequence, mediates effects of cAMP on transcription

50
Q

CREB

A

cAMP response element binding protein

dimerises, binds to CRE
phosphorylation of CREB by PKA promotes dimerisation and enhances transcriptional activation

51
Q

PGC-1

A

transcriptional coactivator upon which hormonal control of liver glucose metabolism converges,
induced in liver by fasting and upregulates PEPCK, G6Pase, F16BPase

52
Q

glucose-responsive TF in the liver

A

ChREBP=a TF which binds ChRE in the PK promoter. DNA binding is inhibited by PKA and AMPK

53
Q

metabolic response to hypoxia

A

induction of the TF HIF1 which increases expression of glycolytic enzymes

54
Q

2 ways HIF functions as a TF

A
  • oxygen promotes HIF degradation: a prolyl-4-hydroxylase uses oxygen to hydroxylate HIF1a. this promotes recognition by the VHL tumour suppressor protein, part of a ubiquitin ligase complex so pomoting HIF1a proteolysis

Hydroxylation at an asparagine residue blocks interaction with the CTD of p300/CBP coactivators

55
Q

tumour metabolism

A

Wahrburg effect - tumours have high rates of aerobic glycolysis, even in the presence of oxygen

56
Q

p53 and glycolysis in normal cells

A

activation of p53 inhibits glycolysis by activating TIGAR
TIGAR has F26BPase activity - inhibiting glycolytic flux instead diverts flux into the pentose phosphate pathway, can produce NADPH and protect against oxidative stress

57
Q

pyruvate kinase in tumour cells

A

isoform called PKM2 is expressed
phosphotyrosine motifs produced by GF signalling bind PKM2, releasing F16BP, an allosteric activator. this causes build-up of upstream intermediates and diversion of glucose into lipid synthesis

58
Q

PGAM1 in tumour cells

A

phosphoglycerate mutase 1 - expr neg reg by p53, controls levels of 3- and 2- phosphoglycerate. increases flux in the PPP and serine biosynthesis

59
Q

HIF1 in tumour cells

A

active as tumours often have chronic hypoxia. HIF1 stabilises p53, turns on glycolysis and off flux in the TCA cycle
= by inducing PDK1, a protein kinase which phosphorylates and inactivates PDH

60
Q

PKM2 in cell’s response to oxidative stress

A

enzyme oxidised upon oxidative stress, decreasing its activity, which diverts flux into the PPP

61
Q

link between regulation of cell cycle and cell metabolism

A

D cyclins and their CDKs are active in G1 and needed for cell division. phosphorylation of PFK1 and PKM2 by cyclinD3-CDK6 inhibits these enzymes, increasing flow of intermediates into the PPP and serine biosynthesis pathways as needed for cell growth/ division

62
Q

cryo electron tomography

A

collect multiple projection images of a thick, vitrified specimen, construct 3D images
resolution limit 4-5 nm so can only observe large protein complexes - but if a macromolecule’s structure is available, can use pattern recognition techniques to identify

63
Q

mechanisms of compartmentation

A

sequetration within cellular organelles

compartmentation by binding

64
Q

problem with breaking open cells and measuring metabolite concentrations

A

are measuring total concentration, which may be much greater than free conc in the cytosol

65
Q

compartmentation by binding

A

muscles have low free cytosolic ADP due to binding of ADP to actin

66
Q

how does a metabolite gradient form firefly luciferase + ATP

A

firefly luciferase shows ATP-dependent luminescence so can be used as a probe for intracellular ATP concentration

67
Q

elevated glucose concentrations and pancreatic B cells

A
  • increased glucose leads to increased glycolysis and TCA flux so elevated ATP.
  • closure of ATP-sensitive K+ channels, PM depolarisation, Ca2+ influx through VG Ca2+ channels and insulin secretion by Ca2+ mediated exocytosis

changes in PM and mitochondrial ATP were closely matched, suggesting mito are close to PM and provide a localised pool of ATP. mito may also have special access to Ca2+, which activates TCA.

68
Q

protein-protein interactions

A

protein concentrations in vivo are very high - may enable protein-protein interactions which are not possible in dilute cell extracts

69
Q

substrate channeling

A

enzyme complex formation - substrates are passed between enzyme active sites without fully equilibrating with the bulk phase.

70
Q

advantages of substrate channeling

A
  • high flux with low int conc
  • isolate ints from competing rxns
  • protect unstable intermediates
  • faster response
  • regulation of flux
71
Q

example of substrate channeling - hexokinase

A

brain HK is associated with mito

skeletal muscle associates with mito in an insulin dependent fashion - HK binds porinwhich forms a pore in the membrane through which metabolites can pass. HK has preferential access to ATP generated within the mitochondria - this coordinates the initial step of glycolysis with mito OXPHOS. (shown by supplying mito with 32P and unlabelled ATP)

72
Q

creatine phosphate shuttle

A
  • in skeletal muscle, there are creatine kinase isoforms associated with the myofibril M band ATPase and inner mitochondrial membrane
  • mitochondrial isoform generates PCr at the mitochondria, preferentially using mitochondrial-derived ATP.
  • The PCr diffuses to the myofibrils and is used to phosphorylate ADP to ATP by the cytosolic creatine kinase
  • creatine diffuses back to the mitochondria to be reused
  • shuttle is effective as though there are diffusion gradients for ATP to the myofibril and ADP to the mitochondria, their concentrations are low: Cr and PCr make more effective transport molecules as they have higher concentrations
  • this is how netATP transport occurs.
73
Q

GPDH1 in drosophila flight muscle

A
  • GPDH1 is an isoform of glycerol 3 phosphate DH localised to the Z discs and M lines of drosophila flight muscle. results in colocalisation of aldolase and GAPDH
  • this localisation is due to a tripeptide at the CTD of GPDH1 - expression of a different isoform lacking this tripeptide does not localsie. aldolase/ GAPDH also don’t localise - flies couldn’t fly despite having almost normal levels of these enzymes
74
Q

PI3K regulation of glycolysis through mobilisation of aldolase

A

GFs/ insulin stimulate activation of Rac via PI3K. leads to distruption of actin cytoskeleton, release of alsolase which is bound to filamentous actin
increases aldolase activity and glycolytic lfux

75
Q

glycogen synthase and glucokinase mobilisation

A
  • resting liver - glycogen synthase not localised
  • presence of glucose - glycogen synthase migrates to the periphery. glucokinase colocalises
  • glycogen first laid down at periphery
76
Q

where do metabolic pathways come from?

A

pathways are evolutionarily ancient and happen slowly non-enzymatically,eg in conditions mimicking the archaean ocean environment

77
Q

topology of metabolic networks

A

scale free networks linked together by a few highly connected substrates (coenzymes)

78
Q

features of scale free networks

A
  • probability that a given substrate participates in k rxns follows a power law distribution (rather than a poisson distribution for a random network)
  • any 2 nodes are connected by relatively short paths (enzymatic reactions), average is 3 (indep of network size)
79
Q

measuring interconnectivity of a scale free network

A

network diameter - shortest biochemical pathway averaged over all pairs of substrates - remarkably small

80
Q

elementary flux modes

A

break-down of metabolic pathway, the smallest sub-networks which enable the metabolic system to operate at steady state

81
Q

network robustness

efficiency

A

related to number of elementary modes

(resistance to effect of mutation)
but increasing number of elementary modes comes at an energetic cost, ie must synthesise more enzymes - need balance
mainly get network redundancy through gene duplication, have isoenzymes where high flux is needed

82
Q

which enzymes of a pathway have potential to control flux?

A

enzymes which catalyse a reaction whose rate is comparable to pathway flux, far from equilibrium

83
Q

mass action ratio

A

[products]/[substrates]

84
Q

methods to identify flux-controlling enzymes in a metabolic pathway

A
  • enzymes with a low Vmax - assume these are rate-limitin. however this suggests aldolase and enolase for heart muscle glycolysis too
  • identify enzymes catalysig reactions far from equilibrium (mass action ratios much less than the equilibrium constants) - suggests usual 3
  • search for cross-over points - when pathway flux is stimulated, there will be a decrease in concentration of intermediates prior to the controlling enzyme and increase in concentration of intermediates after.
  • look for control points at start of pathways/ immediately after branchpoints - this is a good place for control as it prevents accumulation of later intermediates. eg PFK1 catalyses the first committed step in glycolysis
85
Q

how can we quantify the degree of control exerted by each enzyme in a pathway?

A

metabolic control analysis

86
Q

metabolic control analysis

A

links properties of a metabolic pathway (eg flux, metabolite concs) to activities of component enzymes

87
Q

flux control coefficient

A

fractional change in pathway flux due to a fractional change in enzyme concentration

sum of the flux control coefficients for all enzymes in a linear pathway is 1

shows the level of control an enzyme has over the total flux, this changes with different flux levels

flux control is normally distributed throughout all enzymes in the pathway, there is not one truly rate-limiting enzyme

88
Q

true rate-limiting enzyme

A

flux control coefficient = 1

but for most systems, flux control s distributed throughout the pathway

89
Q

determining FCCs of enzymes/ transporters of mitochondrial OXPHOS

A

titrate their activities with inhibitors

flux control shown to be distributed, this distribution depends on rate of respiration

90
Q

studying flux in the TCA cycle - citrate synthase

A

disrupt chromosomal gene, transform cells with a plasmid with CS gene and tac promoter (trp+lac) - vary the concentration of IPTG to alter levels of CS expression
cycle flux close to 0 when incubated with glucose and high/ equ when incubated with acetate.
(FCC=slope of line, detect in WT steady state)

91
Q

why use Metabolic Control Analysis?

A
  • test whether an enzyme thought to be important in vitro is really important in a cell
  • dispels simple notions eg that a non-equilibrium enzyme is one with a high FCC
  • applications in biotech - metabolic pathway engineering
  • help choose drug targets
92
Q

tryptophan biosynthesis - pathway engineering

A

transforming cells with plasmids overexpressing 1/5 enzymes does not affect rate of tryptophan biosynthesis, however transforming with a plasmid which expresses all 5 enzymes does

93
Q

metabolome

A

metabolite complement of a cell/ tissue

94
Q

changing concentration of an enzyme …

A

little effect on pathway flux

large effect on metabolite concentrations, sum to 0 - more easily detected

95
Q

fluorescence

A

emission of radiation when a molecule in an excited state returns to its ground state, normally appears at a longer WL than the incident light as some vibrational energy is lost to the surroundings

96
Q

why is fluorescence so sensitive

A

no background from the excitiation source as detection wl is different

97
Q

types of modern fluorescence microscopy

A

wide field, confocal, multi-photon, light sheet

98
Q

confocal fluorescence microscopy vs wide field

A

wide field is low cose, low photobleaching but confocal has better depth resolution, producing images as defined stacks which can be compiled into a 3D image

99
Q

multi-photon fluorescence microscopy

A

better depth resolution than confocal
… if 2 long WL photons hit a fluorophore at the same time, the energy is combined
longer WL laser gives better penetration through tissue + causes less damage to specimen

100
Q

light sheet fluorescence microscopy

A

even better depth resolution

laser light source orthogonal to objective, only illuminate a very thin sheet of the tissue in same plane as imaging objective’s focal plane
- optical sectioning reduces background so gives high-contrast image. reduces photodamage/ stress on sample, can look at large specimen

101
Q

3 types of super-resolution microscopy

A

SIM: structured illumination
STED: stimulated emission-depletion
PALM/ STORM single molecule localisation

102
Q

SIM: structured illumination

A

sample is excited by laser passing light through optical grating, non-uniform illumination, creating striped interference pattern,moire fringe. use info from structures below the diffraction limit to generate coded images which must be combined mathematically.

103
Q

STED: stimulated emission-depletion

A

first laser excites fluorophore,
donut shaped depleting laser excites electrons again so when they return to ground state a different fluorescence wavelength, which s not detected, is emitted. so detect emission from a smaller area of sample.

104
Q

PALM/ STORM single molecule localisation

A

use photoactivatable/ photoswitchable dyes/ proteins to limit number of simultaneously emitting particles

  • molecules are detected as diffraction-limited spots as gaussian distribution - know object must be in centre of this
  • use single molecule positions from 1000s of images, eah with different emitters, to build up density map
105
Q

pH measurement

A

fluorescence of dye BCECF at 500nm is brighter at higher pHs
this alone would be unreliable as fluorescence also depends on optical path length
to control for this, also measure fluorescence at 450nm (fluorescence indep of pH here) and calculate ratio 500nm/450nm.

106
Q

Ca2+ measurement

A

fura-2 enters cell in form with esterified carboxyl groups. ester groups cleaved off internally, probe binds Ca2+ with high affinity and selectivity. binding of Ca2+ shifts fluorescence excitation spectrum to shorter WLs, measure ration 350nm:385nm

107
Q

measuring intracellular cAMP

A

use derivative of PKA: regulatory and catalytic subunits both tagged with fluorophore. low cAMP: subunits associate, FRET occurs. cAMP: subunits dissociate, no FRET so emission at different WL

108
Q

FRET: ATP biosensor

A

efficiency of FRET increases in presence of ATP as E subunit of ATP synthase retracts, drawing the 2 fluorophores closer together

109
Q

fluorescence polarisation

A

there is a delay between the absorption and emission of light by a fluorophore, during which it can rotate- use to determine tumbling speed and intracellular viscosity

110
Q

intracellular viscosity/ translational diffusion

A

intracellular viscosity is low, as shown by fluorescence polarisation with small molecules
however translational diffusion of larger molecules is significantly hindered

111
Q

NMR: physical principles

A

nuclei with non-zero spin have a magnetic moment and in the presence of an applied magnetic field, assume discrete energy levels. the magnetic moments of the nuclei process around the applied field . an oscillating magnetic field is applied perpendicular to the static field, which induces transitions of nuclei between the two energy levels, which is detected by the NMR spectrophotometer
???

112
Q

NMR chemical shift

A

nuclei of one element resonate over a range of different frequencies depending on chemical environment
express in ppm to normalise

113
Q

NMR intensity

A

area under a peak is proportional to number of nuclei giving rise to it

114
Q

NMR peak width

A

inversely proportional to spin-spin relaxation time eg which depends on tumbling rate of the nucleus. smaller T2 for a larger molecule so larger line width

115
Q

31-P NMR and bioenergetics

A

eg during exercise, in muscle can see decrease in PCr, shift in Pi as pH decreases, constant ATP concentration
rate of PCr resynthesis after exercise = measure of muscle oxidative capacity
???

116
Q

NMR imaging

A

MRI can give anatomical information through the mapping distribution of water molecules
magnetic field gradient is applied across sample, resonance frequency of water protons varies depending on their spatial position within the gradient.

117
Q

functional MRI

A

MRI can give anatomical information through the mapping distribution of water molecules

  • frequency at which water resonates depends on their position in the magnetic field gradient
  • increased brain activity increases glucose use and blood flow to that part of the brain more than oxygen consumption is increased - so oxygen level increases, deoxyHb decreases.
  • deoxyHb is paramagnetic so influences the relaxation of nearby water molecules
  • decreased deoxyHb increases MRI signal intensity in nearby brain areas
118
Q

greater dynamic response???

A

???

BMB (5 decks)

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