Metabolism
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Overheating after overdosing on E - and slimming by taking dinitrophenol
Key points from this exercise:
The aim of oxidising metabolic fuels, and hence the aim of energy yielding metabolism, is to permit the phosphorylation of ADP to ATP, so permitting the various energy requiring processes (ion transport, muscle contraction, protein synthesis and endothermic reactions) to occur.
The main factor controlling the oxidation of metabolic fuels is the availability of ADP, reflecting the utilisation of ATP in energy requiring processes.
Chemically, oxidation is the process of removing electrons from a molecule - either electrons alone or, more commonly with organic compounds, removal of electrons and hydrogen ions (protons), so that oxidation of organic compounds is the removal of hydrogen.
Reduction is the reverse - the addition of electrons, either alone or, more commonly with organic compounds, addition of electrons and hydrogen ions (protons), so that reduction of organic compounds is the addition of hydrogen.
Metabolic fuels undergo oxidation by removal of hydrogen (protons and electrons) by transfer to an intermediate hydrogen carrier - either the nicotinamide nucleotides NAD and NADP or a flavin coenzyme.
Cells contain very small amounts of these coenzymes, which are rapidly re-oxidised in the mitochondrial electron transport chain.
Oxygen is not directly involved in the oxidation of metabolic fuels, but the final reaction of the electron transport chain is the reduction of oxygen to water.
Measurement of oxygen consumption provides a way of following mitochondrial metabolism.
Mitochondria do not consume a significant amount of oxygen, even if substrate is added, unless ADP is also added. The process of substrate oxidation and oxygen consumption is obligatorily linked to the phosphorylation of ADP to ATP.
Malate reduces NAD, and there are three sites associated with phosphorylation of ADP to ATP when NADH is re-oxidised in the mitochondrial electron transport chain. Succinate reduces a flavin, and there are only two sites associated with phosphorylation of ADP to ATP when reduced flavin is re-oxidised in the mitochondrial electron transport chain. This means that for the same amount of ADP phosphorylated to ATP, more substrate will be oxidised, and more oxygen will be consumed, when succinate is the substrate than when malate is the substrate.
The electron transport chain consists of a series of compounds, each of which is reduced by the carrier preceding it, and is reoxidised by reducing the next carrier in the chain. The final carrier is reoxidised by reducing oxygen to water.
The ratio of ADP phosphorylated : oxygen consumed (the P:O ratio) is not an integer; when malate is the substrate the ratio is ~2.5, and when succinate is the substrata the ratio is ~1.5.
Eleven protons are pumped across the crista membrane into the crista space as the carriers of the electron transport chain from NADH undergo reduction and re-oxidation.
These protons re-enter the mitochondrial matrix through a membrane spanning region of the ATP synthase. As they do so, they cause the core of the enzyme to rotate, forcing the active sites of the enzyme to catalyse the next stage of the reaction of ATP synthesis. The enzyme has three active sites, and at any time, one is binding ADP and phosphate, one is catalysing the condensation to form ATP and the third is expelling ATP.
Weak acids render the crista membrane permeable to electrons, so uncoupling electron transport from oxidative phosphorylation and permitting uncontrolled oxidation of substrate until all the available oxygen has been consumed.
Uncoupling proteins in brown adipose tissue and muscle are important in maintenance of body temperature - the process of non-shivering thermogenesis.