Metabolism Flashcards
Explain a what a disulphide bridge is
A covalent bond between two cysteines where the SH groups are oxidised.
What do chaperones do
Can be present in protein folding, ensuring it continues along the most energetically favourable route.
Why is NAD+ a co-enzyme
It has no catalytic activity of its own and only functions after binding to an enzyme.
How is pyruvate converted into ethanol?
Converted to ethanal by pyruvate decarboxylase; converted to ethanol by alcohol dehydrogenase.
Where is GTP produced in the Krebs cycle?
Conversion of succinyl-CoA to succinate, producing CoA and requiring water. Catalysed by succinyl-CoA synthetase
What is A-SCS and where is it found?
An isoform of succinyl-CoA synthetase which catalyses the conversion of succinyl-CoA to succinate, producing ATP rather than GTP. It is found in skeletal and cardiac muscle
Where are the enzymes in the TCA cycle found?
All in the mitochondrial matrix, except succinate dehydrogenase which is found in the inner mitochondrial membrane
Define transamination
Reaction in which an amine group is transferred from one amino acid to a keto acid to form a new pair of keto and amino acids.
What molecules and enzymes are involved in the glycerol phosphate shuttle? How does the shuttle work?
DHAP (dihydroxyacetone phosphate) and glycerol-3-phopshate. Cytoplasmic and mitochondrial glycerol-3-phosphate dehydrogenase. FADH2 produced which communicates directly with ubiquinone.
What is the Warburg effect?
The preferential generation of lactate even under conditions of ample O2.
Name the 3 enzymes in the pyruvate dehydrogenase complex
Pyruvate decarboxylase
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase
Describe how the pyruvate dehydrogenase complex works
- Decarboxylation of pyruvate by pyruvate decarboxylase to produce hydroxyethyl TPP.
- Oxidation and transfer to lipoamide to give acetyl-lipoamide.
- Transfer of the acetyl group to CoA.
- Regeneration of oxidised lipoamide (reactions 2-4 are all catalysed by Dihydrolipoyl transacetylase.
- Regeneration of oxidised FAD, regenerating NADH, by the enzyme Dihydrolipoyl dehydrogenase.
What is (thiamine pyrophosphate) TPP?
A derivative of vitamin B which readily loses a proton to react with pyruvate to from hydroxyethyl-TPP. Catalysed by pyruvate dehydrogenase;
Which type of processes use NADPH as a co-enzyme?
Anabolic processes
Define substrate level phosphorylation
Direct transfer of a high-energy phosphate group from an intermediate to ADP to produce ATP.
What does the proton-motive force which drives protons from the intermembrane space back into the matrix consist of?
A pH gradient AND a transmembrane electrical potential.
Name the 3 complexes and 2 mobile carriers of the ETC.
NADH dehydrogenase complex, cytochrome b-c1 complex, cytochrome oxidase complex.
Co-enzyme Q (ubiquinone) and cytochrome C.
How is it ensured electrons travel in the right direction down the ETC?
Each unit in the chain has a higher affinity for electrons than the previous unit.
How is ubiquinone confined to the inner mitochondrial membrane?
It has a hydrophobic tail
What does a negative redox potential indicates?
A tendency to donate electrons.
Why does FADH2 produce less ATP than NADH in oxidative phosphorylation?
Succinate dehydrogenase communicates directly with co-enzyme Q, so fewer protons are pumped across the inner mitochondrial membrane per electron.
How does cyanide (and azide) act as a metabolic poison?
It has a high affinity to the ferric (3+) haem group in the cytochrome oxidase complex. It’s binding blocks the flow of electrons through the ETC, stopping ATP production.
How does malonate act as a metabolic poison?
Malonate closely resembles succinate so is a competitive inhibitor for succinate dehydrogenase. By inhibiting the oxidation of succinate to fumarate, the flow of electrons is reduced.
How do aromatic weak acids, such a DNP, uncouple oxidative phosphorylation from ATP synthesis?
DNP can cross the membrane in its undissociated form: hence it accepts a proton on the intermembrane side, crosses the membrane and releases the proton into the matrix. This dissipates the proton gradient. This causes the ETC to run uncontrollably, producing lots of heat as waste energy.
Describe how the uncoupling of oxidative phosphorylation can be regulated (non-shivering thermogenesis).
UCP-1 / Thermogenin is a channel that can be activated by a drop in core body temperature. It allows protons to bypass ATP synthase, releasing heat from the dissipation of the proton gradient.
Recall B-oxidation.
Fatty acid –> acyl-CoA using 2 ATPs.
Acyl group transferred to carnitine by carnitine acyl-transferase. Acyl Carnitine crosses into the matrix using a translocase.
Fatty acyl-CoA then oxidised by acyl-CoA dehydrogenase, giving FADH2.
Hydrolyses
Oxidised to give NADH
Thiolysis using B-ketothiolase –> acetyl-CoA produced
