CBI 7: Glycolysis and Gluconeogenesis Flashcards
Give the summary equation of the aerobic respiration of glucose
What are the four metabolic processes that allow glucose to produce ATP?
- glycolysis
- oxidative decarboxylation
- TCA / Krebs cycle
- oxidative phosphorylation and electron transport chain
Give the overall equation of glycolysis and briefly describe glycolysis
- the first step of respiration, where glucose is broken down
- occurs in the cytosol
- divided into three major steps with a total of ten enzyme-catalysed reactions
- one glucose molecule form two pyruvate
- 2NAD+ is reduced to 2NADH
- 2 ATP is formed from 2ADP
What are the three steps of glycolysis called?
- The investment phase
- Break down into two C3- fragments
- Payoff phase
Give an overview of the first step of glycolysis, the investment phase
- called investment phase because two ATP is consumed to form two ADP
- there are three steps:
- trapping glucose into the cell (phosphorylation)
- isomerisation into fructose
- second phosphorylation
Explain the first step of the investment phase of glycolysis
Explain the second step of the investment phase in glycolysis
Explain the third step of the investment phase of glycolysis
Give an overview of the second step of glycolysis, the lysis into two C3-units
- one molecule of fructose-1,6-bisphosphate forms two molecules of glyceraldehyde-3-phosphate
- only this triose is further metabolised, so the other triose, dihydroxyacetone phosphate is converted
- two steps:
- cleavage of C6-carbohydrate
- isomerisation
Explain the first step of the lysis into C3-units phase of glycolysis
- the cleavage of C6-carbohydrate
- reversible reaction
- easily reversed at cellular conditions
- catalysed by aldolase
- which is formed from the reverse reaction (an aldol condensation)
Explain the second step of the lysis into C3-units phase of glycolysis
- isomerisation of dihydroxyacetone phosphate into glyceraldehyde-3-phosphate
- catalysed by triosephosphate isomerase
- reversible reaction with equilibrium shifted to the right
- because glyceraldehyde-3-phosphate is used in the following step of glycolysis, so it is quickly converted
- as 2 molecules of GP are formed, reactions following this occur twice
Give an overview of the payoff phase of glycolysis
Describe the first step of the payoff phase in glycolysis
Describe the second step of the payoff phase of glycolysis
Describe reactions 3-5 of the payoff phase in glycolysis
What are the two fates of pyruvate
- under normal aerobic conditions, pyruvate will be converted into acetyl-CoA
- it is then further oxidised in the TCA or Krebs cycle
- when no oxygen is around, fermentation takes place
- in yeast and other microorganisms, it is converted to ethanol
- in humans, pyruvate is converted to lactate
What is gluconeogenesis (GNG)?
- The de novo (from the beginning) synthesis of sugars (typically glucose) from metabolic precursors
- synthesised from non-carbohydrates
Where does GNG occur?
What is a consequence of this?
- only in two places:
- the adrenal cortex
- the liver
- the consequence is that glucose made through GNG has to travel through the bloodstream to supply it to the organ that needs glucose
Look over the overview of glycolysis
- which reactions are not bi-directional?
- the ones circled blue
Why are three reactions not bi-directional in glycolysis?
How is this a problem for GNG?
- they are effectively irreversible due to a very negative change in Gibbs energy
- they are highly exergonic
- a lot of energy would be needed to revert those reactions, but this is not available
How is the non-bi-directionality of certain reactions overcome for GNG to occur?
- the use of an alternative set of enzymes is used to bypass/reverse these steps using other biochemical processes
Describe the reverse reaction of glycolysis step 1 in GNG
- which enzyme catalyses the reaction
- where does it occur
- products
- forward reaction in glycolysis uses hexokinase
- reverse reaction in gluconeogenesis is catalysed by glucose-6-phosphatase
- this is a membrane-bound protein in the endoplasmic reticulum (ER)
- therefore, this reaction takes place in the lumen of the ER instead of the cytoplasm
Describe the reverse reaction of glycolysis step 3 in GNG
- which enzyme catalyses the reaction
- products
- forward reaction (glycolysis): catalysed by phosphofructokinase
- reverse reaction (GNG): fructose-1,6-biphosphatase
Describe the reverse reaction of glycolysis step 10 in GNG
- which enzyme catalyses the reaction
- where does it occur
- products
- forward reaction (glycolysis): pyruvate kinase
- reverse reaction (GNG): pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEP-CK)
- requires two separate enzyme-catalysed reactions
- pyruvate is first converted into oxaloacetate
- in the mitochondrial matrix
- then converted into malate
- the only way to transport oxaloacetate from the mitochondrial matrix into the cytoplasm (via malate-aspartate-shuttle)
- in the cytoplasm, malate is converted back into oxaloacetate then decarboxylated and phosphorylated by the phosphoenol pyruvate carboxykinase
- these two reactions require energy in the form of ATP and GTP
- to form glucose, we need two molecules of pyruvate
- therefore, these energy-consuming reactions must occur twice
What is the overall equation for GNG?
When is each reactant used?
What are substrates, apart from pyruvate, can be used as the starting substrate in GNG?
- lactate (skeletal muscle)
- glucogenic amino acids (all except leucine and lysine)
- glycerol (lipolysis)
Define catabolic and anabolic reactions
- catabolic reactions: break down molecules into smaller subunits and release energy
- anabolic reactions: require energy to facilitate the synthesis of complex molecules from simple/smaller subunits
What is normoglycaemia?
- the normal range of blood glucose levels, typically between 4-8mM
What happens to blood glucose levels after a meal?
What metabolic processes are switched on?
- after a meal (known as the postprandial period), blood plasma glucose levels increase as it is absorbed
- this is hyperglycaemia
- it then decreases as glucose is taken up by different cells/organs
- the glucose taken up can be used as a substrate for glycolysis
- glycolysis is a catabolic pathway that will be switched on with high levels of glucose in the blood
What happens to blood glucose levels in starvation mode?
What metabolic processes are switched on?
- when there is not much glucose in our bloodstream (hypoglycaemia), there is a need to produce glucose as an energy source
- glycolysis is switched off
- gluconeogenesis is switched on to produce glucose and maintain normal glucose concentrations
What are the two main regulation processes to maintain a stable blood glucose level?
- fast regulation
- slow regulation
Explain the fast regulation process of maintaining blood glucose levels
- the enzymes involved in glycolysis and GNG are critical, so they can be inhibited/activated to regulate the processes
- the concentration of ADP or ATP are effectively a measure of the energy availability in the cell
- only two steps are strongly regulated (see diagram)
Explain the slow regulation process of regulating blood glucose levels
What are some other metabolic substrates that can produce pyruvate or acetyl-coA?
- carbohydrate
- proteins
- lipids
How can carbohydrates be an alternative metabolic substrate?
How can proteins act as an alternative metabolic substrate?
How can lipids act as an alternative metabolic substrate?
Define the investment phase of glycolysis
- steps in glycolysis that require the input of energy, provided by the hydrolysis of ATP
Define the payoff phase of glycolysis
- steps in glycolysis that produce energy in the form of ATP and NADH
Define substrate-level phosphorylation
- a phosphate group is transferred from high energy substrate to ADP to form ATP
