Metabolic poisons Flashcards
Why is mitochondrial respiration dependent on ADP?
ADP is needed to generate ATP using ATP synthase.
As substrates move along the ETC, H+ are transported across the inner mitochondrial membrane giving a greater [H+] on the outer side of the membrane. The electrochemical gradient represents a temporary store of potential energy that is used by ATP synthase to phosphorylate ADP to ATP. The metabolic coupling of the ETC and oxidative phosphorylation ensures that substrates are only metabolised when there is a demand for ATP.
So, oxygen consumption only occurs in the presence of substrate and ADP.
Why is the rate of respiration in the presence of succinate and
ADP greater than with glutamate plus malate and ADP?
Malate feeds electrons into the ETC via the first ETC complex, NADH dehydrogenase complex, and so can generate 3 ATP for each oxygen atom reduced to water.
Oxidation of succinate feeds electrons into the chain via FADH2 and succinate dehydrogenase (part of complex II). This utilised only two of the phosphorylation sites and hence only produces 2 ATP for every oxygen atom reduced to water.
So to generate the same amount of ATP, more succinate must be oxidised than malate and glutamate so more oxygen is used hence the rate of respiration is higher.
What do the data allow you to conclude regarding the metabolic effect of DNOC?
DNOC and DNP can pass readily across the inner mitochondrial membrane in their undissociated form (DNOC-H) thus dissipating the electrochemical gradient.
In the case report, why were the respiratory rate and body
temperature elevated?
DNOC uncouples mitochondrial respiration so that the ETC runs uncontrollably and unproductively.
Due to the uncoupling of ATP Synthase from the ETC, there is an accumulation of H+ in the intermembrane space.
This potential energy is released as heat.
Pulmonary ventilation rate increases because the body is trying to deliver more oxygen to respiring cells to increase ATP production.
Eventually organs fail causing death.
Can you provide explanations for why the DNOC caused absence of body fat, rapid onset of rigor mortis and the femur containing red marrow?
The fatty acids and triacylglycerols stored in adipose tissues are used in respiration.
The excessive oxygen consumption that accompanies this leads to tissue hypoxia. The body tries to overcome this tissue hypoxia by increased pulmonary ventilation and erythropoesis in bone marrow (red marrow).
To relax the muscle fibres before the next power stroke, the ADP must be displaced by incoming ATP. DNOC poisoning greatly decreases the concentration of ATP so the contractile system is left contracted.
In the early 20th century substances with this action (including
DNOC) were tried therapeutically at low doses to stimulate
metabolism and promote weight loss. Why do you think the
licence for such use was withdrawn?
Dosage Issues - the margin between the dose for weight loss and a lethal dose is too narrow to justify its licencing.
What is the relationship between supply and demand of ATP?
There is a direct relation between the supply of utilisable energy in the form of ATP and the demand for energy use at any one time. ATP is not made unless ATP is required to drive another process.
Why is it necessary to add glutamate and malate simultaneously as NADH-linked substrates?
Glutamate and Malate are needed for the malate-aspartate shuttle.
The malate-aspartate shuttle transports NADH from glycolysis from the cytoplasm to the mitochondrial matrix.
The oxaloacetate concentration in vivo is exceedingly low whereas malate concentration is relatively high.
The addition of malate alone would result in the build up of oxaloacetate.
This would inhibit malate dehydrogenase and hence inhibit the production of NADH.
The addition of glutamate allows the excess oxaloacetate to be removed from the mitochondrial matrix via the malate-aspartate shuttle.
