Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors:...
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Transcript of Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors:...
![Page 1: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/1.jpg)
Neuroenergetics
Students:
Idrizi Elita, Tscherrig Jennifer, Pattaroni Céline
Supervisors:
Pellerin Luc, Aitana Morton de Lachapelle
![Page 2: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/2.jpg)
Goals of the project
- Transport / metabolism of glucose and lactate rate-limiting for the brain?
-> Glucose: Barros
-> Lactate: our project!
- Using mathematical tools (matlab) to enforce the hypothesis of lactate
![Page 3: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/3.jpg)
Biological aspects
![Page 4: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/4.jpg)
Glucose - lactate
Glucose: principal energetic substrat of the brain
Lactate: energetic substrat of neurones
Hypothesis of lactate: glucose transformed into lactate by the astrocytes to feed the neurones in extreme conditions of necessity of energy
![Page 5: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/5.jpg)
Aspects biologiques détaillés
![Page 6: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/6.jpg)
Main problems
The transport of glucose is important to define its metabolism and contrariwise
Solve mathematically the transport and metabolism of lactate in the neurones like Barros did it for the glucose
![Page 7: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/7.jpg)
Mathematical aspects
1. Analytical and numerical methods
2. 1st part:
transport and metabolism of glucose
1. 2nd part:
transport and metabolism of lactate
![Page 8: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/8.jpg)
Example: production of a protein
dP/dt = a*Panalytical numerical
P(t) = Po * eat
no formula Analytique
Temps
[P]
P(t)
Numérique
Temps
[P]
Analytical and numerical methods
![Page 9: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/9.jpg)
Transport and metabolism of glucose
Ge+T [GeT] [GnT] Gn+T+E [GnE] Gn*+E
k1, k-1 k2, k-2
d[GeT]/dt = k1* Ge * T - k-1 * [GeT] - k2 * [GeT] + k-2 * [GnT]
Ge extracellular glucose T transporter (GLUT)Gn neuronal glucose E hexokinase
* phosphorylation
![Page 10: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/10.jpg)
1) Metabolism
Gn+H [GnH] Gn*+H k1, k-1 k2
- Hypotheses:1. Hypothesis of pre-equilibrium: rapid equilibration of GnH2. Hypothesis of total hexokinase concentration : Htot = H+[GnH]3. Max speed reached when all enzymes form a complex with Glc:
Vmax = k2*Htot
M-M constant : Km = k2+k-1 / k1
- Solution:vm = (Gn*Vmax)/(Gn+Km) irreversible Michaelis-Menten kinetics
![Page 11: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/11.jpg)
2) Transport
Ge+T [GeT] [GnT] Gn+T k1, k-1 k2, k-2 k3, k-3
- Hypotheses:1. Hypothesis of pre-equilibrium: rapid equilibration of GeT, GnT2. Hypothesis of transport speed: dissociation of GeT and GnT faster than transport (reversible Michaelis-Menten kinetics)dissociation constants : ke=k-1/k1 and kn=k3/k-3
3. Hypothesis of total GLUT transporters concentration: Ttot = T + [GeT] + [GnT]
4. Max speeds for Glc transport inside and outside the neuron : VmaxIN = k2*Ttot and VmaxOUT = k-2*Ttot
- Solution: vt = k2[GeT] – k-2[GnT] =
(VmaxIN*(Ge/ke) - VmaxOUT*(Gn/kn))/(1+(Ge/ke)+(Gn/kn))
![Page 12: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/12.jpg)
Our graphics
![Page 13: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/13.jpg)
Graphics (Barros)
![Page 14: Neuroenergetics Students: Idrizi Elita, Tscherrig Jennifer, Pattaroni C é line Supervisors: Pellerin Luc, Aitana Morton de Lachapelle.](https://reader036.fdocuments.us/reader036/viewer/2022062515/56649ce55503460f949b31b4/html5/thumbnails/14.jpg)
Conclusions: analytical and numerical methods
Analytical results:- Advantages: simple formula
- Desadvantages: many hypotheses
Numerical simulations:To follow (lactate)…