Metabolism 4- ATP production II Flashcards
Describe the important features of acetyl-coA
The thioester bond is a high-energy linkage, so it is readily hydrolysed, enabling acetyl CoA to donate the acetate (2C) to other molecules.
Describe the first reaction of the TCA cycle
Oxaloacetate (4C) is converted into citrate (6C). reaction is catalysed by citrate synthase. The thio-ester linkage of acetyl CoA allows the acetyl group to be readily donated to oxaloacetate.
Describe the second reaction of the TCA cycle
Isomerisation of citrate to give isocitrate. Catalysed by aconitase. OH group moved from 3C to 2C.
Describe the third reaction of the TCA cycle
isocitrate (6C) undergoes oxidative decarboxylation and is converted into a-ketoglutarate (5C) by isocitrate dehydrogenase. One molecule of NADH is produced.
Describe the fourth reaction of the TCA cycle
a -ketoglutarate (5C) undergoes oxidative decarboxylation and is converted into succinyl-CoA (4C). HS-coA produced from the first reaction donates H atom to form NADH. The reaction is catalysed by a-ketoglutarate dehydrogenase complex.
Describe the fifth reaction of the TCA cycle
succinyl-CoA (4C) is converted to succinate (4C). CoA is displaced by a phosphate molecule which is subsequently transferred to GDP to form GTP. Reaction is catalysed by succinyl CoA
synthetase. Water is needed to hydrolyse thioester bond.
In which tissues is GTP produced.
G-SCS, the GTP forming version is found predominantly in tissues that catalyse anabolic reactions e.g. liver
An alternative isoform of succinyl CoA synthetase (A-SCS) is found in skeletal and cardiac muscle and catalyses the same reaction but generates ATP from ADP.
Describe the sixth reaction of the Krebs Cycle
succinate (4C) is oxidised into fumarate (4C) by succinate dehydrogenase. FAD is reduced to FADH2
Describe the seventh reaction of the Krebs Cycle
Fumarate is converted into malate, catalysed by fumarase. Addition of a water molecule, breaking a double bond.
Describe the final reaction of the TCA cycle
The last step. Dehydrogenation of malate to give oxaloacetate, the starting point of the cycle.
Catalysed by malate dehydrogenase- NAD reduced to NADH.
What does each turn of the Krebs cycle produce
Each turn of the cycle produces two molecules of CO2 (waste) plus three molecules of NADH, one molecule of GTP and one molecule of FADH2.
Describe the location of enzymes involved in the TCA cycle
The Krebs cycle enzymes are soluble proteins located in the mitochondrial matrix space, except for succinate dehydrogenase, which is an integral membrane protein that is firmly attached to the inner surface of the inner mitochondrial membrane. Here, it can communicate directly with components in the respiratory chain
Describe the importance of reduced cofactors
The majority of the energy that derives from the metabolism of food is generated when the reduced coenzymes are re-oxidised by the respiratory chain in the mitochondrial inner membrane in a process known as oxidative phosphorylation (lecture 5).
The Krebs cycle only operates under aerobic conditions, as the NAD+ and FAD needed are only regenerated via the transfer of electrons to O2 during oxidative phosphorylation.
What is the general strategy of amino acid degradation
The general strategy of amino acid degradation is to remove the amino group (which is eventually excreted as urea) whilst the carbon skeleton is either funnelled into the production of glucose or fed into the Krebs cycle. Degradation of all twenty amino acids gives rise to only seven molecules, pyruvate, acetyl CoA, acetoacetyl CoA, a-ketoglutarate, succinyl CoA, fumarate and oxaloacetate.
What is transamination
Defined as a reaction in which an amine group is transferred from one amino acid to a keto acid thereby forming a new pair of amino and keto acids.
Carried out in the liver.
Describe the metabolism of alanine
Alanine (C3) undergoes transamination by the action of the enzyme alanine aminotransferase.
Alanine a-ketoglutarate — pyruvate glutamate
Pyruvate can enter the TCA cycle, while glutamate is re-converted to a-ketoglutarate- used in TCA. by glutamate dehydrogenase, generating NH4+ which is ultimately converted to urea.
persistently high levels of alanine dehydrogenase can be diagnostic of hepatic orders such as Hep C.
Describe the glycerol phosphate shuttle
Electrons from NADH, rather than NADH itself are carried across the mitochondrial membrane via a shuttle.
Cytosolic glycerol 3-phosphate dehydrogenase transfers electrons from NADH to DHAP to generate glycerol 3-phosphate.
- A membrane bound form of the same enzyme transfers the electrons to FAD. These then get passed to co-enzyme Q, part of the electron transport chain (lecture 5).
Describe the malate-aspartate shuttle
This system uses two membrane carriers and four enzymes.
A hydride ion (H-) is transferred from cytoplasmic NADH to oxaloacetate to give malate, a reaction catalysed by cytosolic malate dehydrogenase (MDH).
Malate can be transported into the mitochondria where it is rapidly re-oxidised by NAD+ to give oxaloacetate and NADH (catalysed by mitochondrial MDH).
A - alpha-ketoglutarate transporter, exchanges alpha-ketoglutarate for malate. malate in
B - glutamate/aspartate transporter, exchanges glutamate for aspartate aspartate out.
Describe the role of transamination in the malate-aspartate shuttle
glutamate + oxaloacetate — aspartate + a-ketoglutarate
How many ATP molecules does NADH and FADH2 produce
Re-oxidation of the reduced co-factors NADH and FADH2 by the process of oxidative phosphorylation (lecture 5) yields the following:
Three ATP molecules are formed by the re-oxidation of each NADH molecule.
Two ATP molecules are formed by the re-oxidation of each FADH2 molecule.
Therefore, from the Krebs Cycle:
Oxidation of 1 X acetyl CoA molecule gives 3 x NADH + 1 x FADH2 + 1x GTP = 12 ATP
How can glycolysis and TCA cycle act as starting points for biosynthesis
A lot of the intermediates can be used as starting molecules for the biosynthesis of macromolecules.
Describe how catabolic reactions are kept separate from anabolic reactions
NADPH takes part in anabolic reactions, whereas NADH takes place in catabolic reactions.
The use of different co-factors for sets of reactions allows electron transport in catabolism to be kept separate to that of anabolism.
Describe the difference between NADP and NAD
NADP+ is a relative of NAD+, differing only by a phosphate group attached to one of the ribose rings.
Like NAD+, NADP+ can pick up two high energy electrons and in the process, a proton (H+) collectively known as a hydride ion (H-).
The phosphate group of NADP+ does not participate in electron transfer, but gives it a slightly different conformation, meaning that it will bind to different enzymes than NAD+.
The hydride ion is held in a high-energy linkage, allowing it to be easily transferred to other molecules.
Describe some of the reactions in which NADP is a cofactor
Biosynthesis of cholesterol and thymidine.
