Week 2 - glycolysis & glycogen metabolism Flashcards
What is glycolysis?
- Glycolysis is the process that converts some of the metabolic energy of glucose molecules into ATP

What are the phases of glycolysis?
Briefly explain what happens in both of them
- There are two phases of glycolysis
- In the first phase a series of five reaction convert glucose into two molecules of glyceraldehyde-3-phosphate
- This phase consumes two molecules of ATP
- In the second phase two molecules of glyceraldehyde-3-phosphate are converted into two molecules of pyruvate
- Results in the production of four ATP molecules

What is the net production of ATP during glycolysis for one molecule of glucose?
- Net production is + 2 molecules of ATP per glucose molecule since two ATP are used up and four ATP are produced
Outline, in detail, the first reaction of glycolysis
- Glucose is phosphorylated to glucose-6-phosphate by either hexokinase or glucokinase
- Occurs in the liver since glucokinase is specifically located here
- This reaction is thermodynamically unfavourable and requires the energy from the hydrolysis of ATP to drive the reaction forward
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What is the importance of the first step of the first stage of glycolysis?
- The phosphorlyation of glucose to glucose-6-phosphate is important since the transport proteins that transport glucose into the cell cannot bind/transport glucose-6-phosphate meaning phosphorylated cannot leave the cell
- Furthermore the phosphorylation of glucose ensures that the intracellular concentration of glucose is low and the concentration gradient favours the diffusion of glucose into the cell
Outline the second rection in the first stage of glycolysis
- The second step is the isomerisation of glucose-6-phosphate to fructose-6-phosphate
- This reaction is catalysed by the enzyme phosphoglucoisomerase (aka glucose phosphate isomerase)

Outline the third reaction in the first stage of glycolysis
What is the importance of the enzyme that catayses this reaction?
- 3rd step is the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate
- Reaction is catalysed by the enzyme phosphofructosekinase (PFK)
- Reaction is coupled with the hydrolysis of ATP which provides the phosphoryl group
- PFK is commonly described as the rate limiting enzyme in the regulation of the rate of glycolysis

What step of glycolysis is the enzyme phosphofructokinase (PFK) involved in?
Why is it important and how is its activity controlled?
- PFK is involved in the second reaction of the first stage of glycolysis
- It is the rate limiting enzyme of glycolysis
- ATP is an allosteric inhibitor of PFK therefore high [ATP] inhibits PFK which decreases its affinity for fructose-6-phosphate and therefore decreases the rate of glycolysis
- Activity of PFK also depends on AMP which serves to revert the inhibition of ATP on PFK
- AMP levels increase as ATP levels decrease which alleviates the inhibitory action of ATP on PFK

Outline the fourth reaction of the first stage of glycolysis
- Fructose-1,6-biphosphate is converted into two triose phosphates
- Glyceraldehyde-3-phosphate (G3P)
- Dihydroxyacetone phosphate (DHAP)
- This reaction is catalysed by fructose biphosphate aldolase
- G3P enters directly into the second phase of glycolysis

Outline the fifth reaction of the first phase of glycolysis
- Dihydroxyacetonephosphate (DHAP) is converted to glyceraldehyde-3-phosphate via triose phosphate isomerase
- Once converted to G3P it enters the second phase of glycolysis

Outline reaction 6 of glycolysis
- Reaction 6 marks the start of the second phase of glycolysis which, overall, results in the net production of ATP
- In reaction 6 glyceraldehyde-3-phosphate is oxidised to 1,3-biphosphoglycerate by the enzyme glyceraldehyde-3-phosphate dehydrogenase
- This reaction results in both the formation of carboxylic-phosphoric anhydride and the reduction of NAD+ to NADH

Outline reaction 7 of glycolysis
- In this reaction 1,3-biphosphoglycerate is converted to 3-phosphoglycerate
- Phosphoglycerate kinase catalyses this reaction by catalysing the transfer of a phosphoryl group from 1,3-biphosphoglycerate to ADP to form ATP

Outline reaction 8 of glycolysis
- Reaction is catalysed by phosphoglycerate mutase
- 3-phosphoglycerate is converted to 2-phosphoglycerate which involves moving the phosphoryl group from C-3 to C-2 by phosphoglycerate mutase

Outline reaction 9 of glycolysis
- The enzyme enolase catalyses the formation of phosphoenolpyruvate (PEP) from 2-phosphoglycerate
- This reaction results in the formation of a water molecule

Outline reaction 10 of glycolysis
- Pyruvate kinase mediates the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP to form ATP and pyruvate
- This reaction requires Mg2+ and is stimulated by K+ and certain other monovalent ions
- This is the final ATP synthesizing reaction of glycolysis

What are the main products of glycolysis?
How may they be processed?
- The main products are ATP, NADH and pyruvate
- Their processing depends on other cellular pathways
- NADH can be recycled to NAD+ by both aerobic and anaerobic pathways
- In aerobic conditions pyruvate enters the tricarboxylic acid cycle (TCA cycle) where it is oxidised to CO2 with the production of additional ATP, GTP, FADH2 and NADH

Briefly describe what happens to pyruvate under anaerobic conditions in different organisms
- Pyruvate is reduced to ethanol in yeast
- In other microorganisms and animals pyruvate is reduced to lactate
- These anaerobic pathways are examples of fermentation
Briefly decribe alcohol fermentation in yeast
Where is this used?
- Alcohol fermentation in yeast entails the decarboxylation of pyruvate to acetaldehyde by pyruvate decarboxylase
- Subsequently NADH reduces the acetaldehyde to ethanol which is catalysed by alcohol dehydrogenase
- The end products of this anaerobic pathways are CO2 and ethanol
- Used in the process of brewing beer and formation of wine
Briefly outline lactic acid formation in animals
- Reduction of pyruvate to lactase occurs in oxygen-limited tissues, i.e. in tissues with limited access to blood flow and rapidly contracting skeletal muscle
- Pyruvte is reduced by lactase dehydrogenase to lactate when skeletal muscles are in anaerobic conditions as all oxygen has been consumed
- Pyruvate cannot be oxidised to enter the TCA cycle - lactate represents the end of glycolysis

What can be the effects of the accumulation of lactic acid in animals?
How is the lactic acid further processed?
- Cramps and muscle fatigue is associated with the accumulation of lactic acid in the muscle
- Majority of lactate is transported out of muscle to the liver where it is used in gluconeogeneis for the re-synthesis of glucose
- Additionally, the production of lactate in skeletal muscles means there is a reduction in the amount of ATP generated and available because the majority is generated by the TCA cycle and oxidative phosphorylation

What other substrates, besides glucose, can enter the glycolytic pathway?
- Other sugars can enter the glycolytic pathway providing that they can be converted into one of the intermediates of glycolysis
- These include:
- fructose
- mannose
- galactose
- glycerol

Give an overview of anaerobic metabolism
- When no oxygen is present, pyruvate produced by glycolysis undergoes the process of fermentation
- This process consisits of reaction which reduce pyruvate to either lactate, an alcohol or an organic acid using the donated e- and H+ from NADH (NADH is oxidised) thus recycling NAD+ for use in glycolysis
- There is no additional energy gain during these reactions and the whole purpose if the fermentation process is to regenerate NAD+
- Anaerobic metabolism occurs in the cyctoplasm
- NADH + H+ ——–> NAD+ + 2e- + 2H+

Describe the difference between the free energy of glucose and the energy released by the fermentation process
- Fermentation results in incomplete oxidation of glucose with a net generation of only 2 ATP molecules per glucose (produced during the glycolysis stage)
- Total free energy of glucose is 686kcal but the fermenation process releases only 2 ATP molecules (14.6kcal) per glucose molecule
- Therefore fermentation releases only 2.1% of the free energy of glucose and the majority of energy is conserved in the product of the fermentation reaction (lactate or alcohol)

Describe different types of fermentation
- The most common type is lactate fermentation which is an energy yielding pathway found in anaerobic bacteria and animal cells (under anaerobic conditions)
- lactic acid is responsible for the taste of yogurt and sour milk
- Alcoholic fermentation commonly associated with yeasts cells and is economically important in food and drink production (break, wine, spirits)
- Propionate fermentation which gives distinctive cheese flavours and aromas
- Butylene glycol fermentation is associated with rancid fats








