100% satisfaction guarantee Immediately available after payment Both online and in PDF No strings attached
logo-home
Samenvatting - BMS42 - Targeting cellular processes to treat disease (BMS42) Summary $8.55
Add to cart

Summary

Samenvatting - BMS42 - Targeting cellular processes to treat disease (BMS42) Summary

 6 views  0 purchase
  • Course
  • Institution

Deze samenvatting bevat alle onderwerpen behandeld tijdens het master vak BMS42 - Targeting cellular processes to treat disease (TCA cycle, oxidative metabolism, anaeorbic glycolysis, mitochondrial biology, isolated human complex I deficiency, small molecules, integrin adhesion and signaling, antib...

[Show more]

Preview 3 out of 21  pages

  • November 27, 2024
  • 21
  • 2024/2025
  • Summary
avatar-seller
BMS42 – Targeting Cellular Processes to Treat Disease




BMS42 – TARGETING CELLULAR
PROCESSES TO TREAT DISEASE




Opleiding: Master Biomedical Sciences
Onderwijsinstelling: Radboudumc




1

, BMS42 – Targeting Cellular Processes to Treat Disease




Content
Energy metabolism............................................................................................................................3
The tricarboxylic acid cycle....................................................................................................................................3
Oxidative metabolism...........................................................................................................................................3
Anaerobic glycolysis..............................................................................................................................................4

Mitochondrial diseases......................................................................................................................4
Mitochondrial biology...........................................................................................................................................4
Pre-clinical drug discovery in academia................................................................................................................5
Isolated human complex I deficiency..............................................................................................................5

Small molecule drug development at Khondrion.................................................................................................6
Drug discovery pipeline...................................................................................................................................6

Integrin adhesion and signaling.........................................................................................................7
Integrin classes and basic integrin structure.........................................................................................................7
Focal adhesion assembly.......................................................................................................................................7
Mechanisms of inside-out and outside-in integrin signaling................................................................................8
Common pathways of integrin and growth factor signaling.................................................................................9
Integrin binding to RGD-binding substrates..........................................................................................................9
Fibronectin binding to integrins on cell surface causes formation of fibronectin fibrils................................9

Integrins in cancer.................................................................................................................................................9
β1 integrin targeting in cancer......................................................................................................................10

αIIbβ3 targeting in cardiovascular medicine.................................................................................................11

α4β7 targeting in IBD....................................................................................................................................11

Biologic development in context of integrins/cell migration.............................................................................11

Targeting tissue regeneration with cell-based therapeutics.............................................................12
Cell-based therapeutics.......................................................................................................................................12

iRATs...............................................................................................................................................15
iRAT1 Week 1: Mitochondrial biology.................................................................................................................15
iRAT2 Week 1: Small molecule development.....................................................................................................18
iRAT3 Week 2: Integrins and cell migration........................................................................................................20




2

, BMS42 – Targeting Cellular Processes to Treat Disease


Energy metabolism
The tricarboxylic acid cycle
Glucose metabolism takes place in the cytosol without the need for oxygen through a process called glycolysis.
It yields a small amount of ATP, and the 3-carbon compound pyruvate. After the transportation of pyruvate into
the mitochondria, the pyruvate dehydrogenase complex (PDC) facilitates the conversion of pyruvate to acetyl-
CoA and CO2. In high blood sugar levels, most acetyl-CoA is derived from glucose, specifically pyruvate.
However, in starvation or fasting states, beta-oxidation contributes to acetyl-CoA production. Acetyl-CoA
undergoes oxidation to CO2 in 8 steps.

1. The TCA cycle starts when the two-carbon molecule acetyl-CoA
combines with four-carbon oxaloacetate to form citrate, a reaction
catalyzed by citrate synthase (CS).
2. Citrate is then converted to isocitrate by aconitase 2 (ACO2).
3. Isocitrate is decarboxylated to alpha-ketoglutarate (αKG) in an NAD +-
dependent manner by isocitrate dehydrogenase 3 (IDH3) or in an
NADP+-dependent manner by isocitrate dehydrogenase 2 (IDH2),
releasing carbon dioxide (CO2).
4. αKG undergoes decarboxylation to succinyl-CoA via the oxoglutarate
dehydrogenase complex (OGDH), producing NADH and releasing CO 2.
5. Succinyl-CoA is then converted to succinate by succinyl-CoA
synthetase (SCS). This is the only substrate-level phosphorylation step
in the TCA cycle, as it is coupled to the generation of GTP or ATP.
6. Succinate is converted to fumarate by succinate dehydrogenase
(SDH) complex, a multisubunit enzyme complex that participates in both the TCA cycle and the
electron transport chain (ETC). SDH reduces FAD to FADH 2, which donates its electrons to complex II.
7. Fumarate is converted to malate by fumarate hydratase (FH).
8. Malate dehydrogenase 2 (MDH2) converts malate to oxaloacetate in an NAD +-dependent manner,
regenerating the starting molecule and supporting the next turn of the cycle.

Oxidative metabolism
Glucose, fatty acids, and amino acids undergo catabolism to feed into the TCA cycle, which generates
substrates for the electron transport chain (ETC). The mitochondrial ETC consists of five protein complexes
integrated into the inner mitochondrial membrane.

1. The TCA cycle in the mitochondrial matrix supplies NADH and FADH 2 to the ETC, each of which donates
a pair of electrons to the ETC via Complexes I and II respectively. The transfer of electrons from
Complex I to the Q cycle results in a net pumping of 4 protons across the inner membrane into the
intermembrane space (IMS). Of note, Complex II does not span the inner membrane and does not
participate in proton translocation.
2. The electrons from either Complex I (2 electrons) or Complex II (2 electrons one at a time) are donated
to ubiquinone (Q) which is reduced to ubiquinol (QH 2). Ubiquinol is oxidized by Complex III allowing
one electron at a time to continue the journey through cytochrome c. For every electron transferred
to cytochrome c, 2 protons (H+) are pumped into the IMS, resulting in 4H+ pumped into the IMS for
every electron pair moved through the cycle.
1
3. Cytochrome c transports electrons to Complex IV where molecular oxygen ( O2) acts as a terminal
2
electron acceptor and is reduced to water. The reduction of one molecule of O 2 requires 4 electrons.
The reduction of O2 to H2O results in the pumping of 4 protons to the IMS, but 2 protons are
consumed in the process, netting a total of 2 H + pumped into the IMS at Complex IV.
4. The movement of protons from the mitochondrial matrix into the intermembrane space in response
to electron transfer creates a proton-motive force (Δp), which is the proton concentration (pH)
combined with the electrochemical proton gradient known as the mitochondrial membrane potential
(ΔΨ). The membrane potential is dissipated by the re-entry of H + back into the matrix through
3

The benefits of buying summaries with Stuvia:

Guaranteed quality through customer reviews

Guaranteed quality through customer reviews

Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.

Quick and easy check-out

Quick and easy check-out

You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.

Focus on what matters

Focus on what matters

Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!

Frequently asked questions

What do I get when I buy this document?

You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.

Satisfaction guarantee: how does it work?

Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.

Who am I buying these notes from?

Stuvia is a marketplace, so you are not buying this document from us, but from seller StudentRU07. Stuvia facilitates payment to the seller.

Will I be stuck with a subscription?

No, you only buy these notes for $8.55. You're not tied to anything after your purchase.

Can Stuvia be trusted?

4.6 stars on Google & Trustpilot (+1000 reviews)

53068 documents were sold in the last 30 days

Founded in 2010, the go-to place to buy study notes for 14 years now

Start selling
$8.55
  • (0)
Add to cart
Added