Metabolic and ATP II Flashcards
How is pyruvate used to make Acetyl Co-A?
Pyruvate + HS-CoA —> Acetyl CoA + CO2
- Using enzyme pyruvate dehydrogenase complex and NAD+ is converted to NADH
- This reaction occurs in the mitochondrion. The acetyl CoA formed is committed to entry into the Krebs’ Cycle.
Structure of Acetyl Co-A
The Thioester bond is a high-energy linkage so it is readily hydrolysed enabling Acetyl CoA to donate acetate (2C) to other molecules.
What is produced in the Krebs cycle overall and therefore how many ATP are formed?
One turn produces: 3 x NADH 1 x GTP 1 x FADH2 2 x CO2
1 NADH = 3 ATP
1 FADH2= 2ATP
So 1 x acetyl coA =
(3xNADH) + (1 xFADH) + (1xGTP) =12 ATP
What is transamination?
Protein Metabolism involves transamination reactions - 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.
Example of protein metabolism involving transamination (using alanine)
Alanine + a-ketoglutarate –> pyruvate + glutamate
- Alanine undergoes transamination by the action of enzyme Alanine Aminotransferase.
- Pyruvate can enter the TCA cycle.
- Glutamate is converted back to a-ketoglutarate by Glutamate Dehydrogenase. This generates NH4+ which is ultimately converted to urea.
How and why is NADH transported?
NADH produced in glycolysis needs to enter the mitochondria to be used by the process of oxidative phosphorylation and to generate NAD+.
There is only a finite amount of NAD+ so unless it is regenerated glycolysis will stop.
Hence, NADH (or more accurately, the high energy electrons of NADH) cross the cytosol into the matrix of the mitochondrion by:
- Glycerol Phosphate Shuttle - skeletal muscle, brain
- Malate Aspartate Shuttle - liver, kidney, heart
How
How does the Malate-Aspartate shuttle work?
-Uses 2 membrane carriers and 4 enzymes
Hydrogen is transferred from cytoplasmic NADH to oxaloacetate to give malate, a reaction catalysed by cytosolic malate dehydrogenase (MDH). Malate is transported into the mitochondria where it is rapidly re-oxidised by NAD+ to give oxaloacetate and NADH (catalysed by mitochondrial MDH). Oxaloacetate and glutmate then undergo transamination to give the pair alpha-ketoglutarate and aspartate, which can exit the mitochondrial matrix via specific transporters in exchange for malate and glutamate respectively
2 antiporters (carrier proteins)
Malate alpha-ketoglutarate antiporter
Glutamate- aspartate antiporter.
Difference between NADPH and NADH
- NADPH takes part in anabolic reactions, whereas NADH takes place in catabolic reactions
- The use of different co-factors for different sets of reactions allows electron transport in catabolism to be kept separate to that of anabolism
What can GTP act as?
It can donate its phosphate group in protein synthesis or signal transduction.
When succinyl-CoA is converted to succinate, GTP is formed. Where in the body is ATP formed from the same reaction?
ATP: skeletal and cardiac muscle
GTP: liver, tissues that catalyse anabolic reactions
Where are most of the enzymes required for the TCA cycle found?
Any exceptions?
These are soluble protein found in the mitochondrial matrix space.
SUCCINATE DEHYDROGENASE is attached to the inner surface of the inner mitochondrial membrane.
What is the maximum theoretical yield of ATP following aerobic respiration of one molecule of glucose?
38
What is the process of degradation of amino acids?
Remove the amino acid whilst the carbon is either funnelled into the production of glucose or fed into the krebs cycle
What does degredation of all 20 amino acids produce?
Only 7 molecules:
- pyruvate
- acetyl coA
- acetoacetyl coA
- a-ketoglutarate
- succinyl coA
- fumarate
- oxaloacetate
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What does high levels of alanine aminotransferase a sign of?
-Hepatic disorders such as Hepatitis C.
How does the glycerol phophate shuttle work?
Enzyme: Glycerol-3-phosphate dehydrogenase.
1. Cytosolic glycerol 3-phosphate dehydrogenase transfers electrons from NADH to DHAP (dihydroxyacetone) 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 .
What is the net reaction in terms of NADH when using malate-aspartate shuttle?
The net reaction in terms of NADH is:
NADH cytoplasmic + NAD+mitochondrial————->
NAD + cytoplasmic + NADH mitochondrial.
How id NADP+ and NAD+ different structurally?
NADP+ is a relative of NAD+, differing only by a phosphate group attached to one of the ribose rings.
Where is NADPH used?
Used as a co factor in the pathway involved in thymidine synthesis.
-also is a co-factor in the biosynthesis of cholestrol.
The c double bond is reduced by transfer of a hydride ion.
Where does malate-aspartate shuttle take place?
primarily in heart and liver
what are the steps for the Krebs cycle?
- Oxaloacetate to citrate using acetyl coA, citrate synthase
- Isomerisation of citrate to give isocitrate
- Oxidation of isocitrate to give a-ketoglutarate, using isocitrate dehydrogenase. NAD+ converted to NADH
- a -ketoglutarate converted to succinyl- coA, converting a-ketoglutarate dehydrogenase complex. NAD+ converted to NADH
- CoA is displaced by a phosphate molecule which is subsequently transferred to GDP to form GTP so succinyl-CoA to succinate using succinyl coA sythetase
- Succinate to fumerate, FAD—FADH2 using succinate dehydrogenase
- Fumerate to malate. Fumerase. Water added to break double bond
- Malate to oxaloacetate. Using malate dehydrogenase. NAD+ to NADH
Where is GTP made for the step reaction from succinyl coA to succinate?
GTP forming version is found predominantly in tissues that catalyse anabolic reactions e.g. liver..G-SCS
succinyl CoA synthetase (A-SCS) is found in skeletal and cardiac muscle and catalyses the same reaction but generates ATP from ADP.
Overall what is produced by glycolysis, PDH complex and TCA cycle in terms of ATP
- 2 ATP + 2 NADH = 8 ATP
- 2 X acetyl coA + 2NADH = 6 ATP
- (6 X NADH) + (2 X FADH2) + (2 X GTP) = 24 ATP
38 ATP
