Glycolysis and the TCA Cycle Flashcards
What are the 6 types of metabolic reaction?
Redox Ligation requiring ATP cleavage Isomerization Group Transfer Hydrolytic Addition or removal of functional groups
Where does glycolysis occur?
The cytoplasm/cytosol
What is the net gain of ATP and NADH from glycolysis?
2
What are the two main aims of glycolysis
Formation and splitting of a high energy compound
Why is initially phosphorylating the glucose important?
It makes it more reactive.
It commits it to the subsequent reactions by giving it a negative charge, preventing it from leaving the cell.
What enzyme converts Dihydroxyacetone into glyceraldehyde 3-phosphate and why is this important?
TPI (Triose phosphate isomerase) as a deficiency in TPI is the only glycolytic enzymopathy that is fatal, with must sufferers dying within the first 6 years of their life.
What are the three fates of pyruvate?
Pyruvate has three main fates:
Alcoholic fermentation
Lactate production
Acetyl CoA production
What is alcoholic fermentation characteristic of and under what conditions does it occur?
Alcoholic fermentation is characteristic of yeasts and can occur under anaerobic conditions.
How does alcoholic fermentation generate NAD+?
Acetaldehyde (ethanal) is reduced by alcohol dehydrogenase to form ethanol. This oxidises NADH and H+ into NAD+.
What is lactate production characteristic of and under what conditions does it occur?
Lactate production is also anaerobic and is characteristic of mammalian muscle during intense activity when oxygen is a limiting factor.
How does lactate production generate NAD+?
Pyruvate is converted to lactate by lactate dehydrogenase, oxidising NADH and H+ into NAD+.
What is the common purpose behind both alcoholic fermentation and lactate production and why?
Allowing NAD+ to be regenerated and thus glycolysis to continue in conditions of oxygen deprivation, conditions in which the rate of NADH formation by glycolysis is greater than its rate of oxidation by respiratory (electron transport) chain.
Apart from lactate production and alcoholic fermentation, what else can happen to pyruvate?
Acetyl CoA can be generated in the mitochondria.
What is special about Acetyl CoA?
It is the building block for many important biological molecules.
It has a high energy thioester bond, allowing it to be easily hydrolyzed and so can easily donate its acetate group.
What is Beri-Beri a result of?
A deficiency of thiamine (derivative of vitamin B1) leading to poor PDH (pyruvate dehydrogenase complex) function, specifically the thiamine pyrophosphate enzyme.
What are the symptoms of Beri-Beri and what organ is particularly vulnerable?
Symptoms include damage to the peripheral nervous system, weakness of the musculature and decreased cardiac output.
The brain is particularly vulnerable due to its heavy reliance on glucose metabolism.
What converts pyruvate into acetyl CoA?
PDH (Pyruvate dehydrogenase complex) which is a mixture of enxymes.
What does the formation of acetyl CoA also form?
NADH
Each turn of the Krebs cycle produces what?
2 CO2 as waste
3 NADH
1 GTP
1 FADH2
The Krebs cycle enzymes are all what (apart from one)?
Water-soluble proteins in the mitochondrial matrix.
Why is it important that the TCA cycle only occurs in aerobic conditions?
The bulk of ATP is generated when the reduced coenzymes are re-oxidised with the help of oxygen (oxidative phosphorylation).
This re-oxidation means that the TCA cycle only operates under aerobic conditions.
Amino acids can also enter the TCA cycle. What must happen to the amino acids first?
Removal of amine group that will later be excreted as urea. The carbon skeleton is then funneled into the production of glucose or fed into the Krebs cycle.
Degradation of all twenty amino acids gives rise to what seven molecules?
Pyruvate Acetyl CoA Acetoacetyl CoA, Alpha-ketoglutarate Fumarate Oxaloacetate Succinyl CoA Acronym to help remember: Proteins And Amino Acids Follow Our Sugars
Protein metabolism involves what main reactions?
Transamination reactions.
What do transamination reactions consist of?
An amine group is transferred from one amino acid to a keto acid forming a new pair of amino keto acids.
NADH produced in glycolysis needs to enter the mitochondria to be utilised by the process of OP and to regenerate NAD+. How does NADH, or more accurately, its high-energy electrons, cross from the cytosol into the matrix of the mitochondria?
The glycerol-phosphate shuttle and the malate-aspartate shuttle.
How does the glycerol-phosphate shuttle work?
In 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.
How does the malate-aspartate shuttle work
Oxaloacetate is converted by MDH (malate dehydrogenase) and NADH into malate which can enter the mitochondria.
In the mitochondria, malate is converted back into oxaloacetate by MDH and NAD+ (which gets turned into NADH, now there is NADH in the mitochondria) which is then converted into aspartate by AT (aspartate transaminase) and glutamate (which gets turned into alpha ketoglutarate).
Aspartate can then leave the mitochondria, where it can be converted by AT and alpha ketoglutarate (which gets turned into glutamate) into oxaloacetate.
How much ATP does NADH later produce?
3
How much ATP does FADH2 later produce?
2
How much ATP does GTP later produce?
1
Overall, how much ATP does the oxidation of one acetyl CoA molecule produce (from later OP)?
12
3NADH = 9 ATP
1FADH = 2 ATP
1GTP = 1 ATP
What is the link between cancer and TCA enzymes?
Mutations in the TCA genes have been shown to decrease TCA activity and enhance anaerobic glycolysis.
The preferential generation of lactate from glucose even under conditions of ample O2 (Warburg Effect) is characteristic of cancerous cells.
