Gluconeogenesis Flashcards
What would be the benefit of synthesising glucose by the body
Highly energy rich molecule which is utilised by the body as a metabolic fuel
Different monosaccharides can be converted into glucose
What process occurs when you aren’t taking in glucose in your diet and glycogen stores are depleted
Gluconeogenesis
Using non-carbohydrate precursors
Where does gluconeogenesis occur
Liver and Kidney
Gluconeogenic precurosrs are molecules that can be used to produce a new synthesis of glucose
These can include?
Glycolysis intermediates
TCA cycle intermediates
carbon skeleton of amino acids
Where molecule does glycerol come from
Released in the hydrolysis of triacylglycerols
How can glycerol be converted into glucose
- It can be phsphorylated to glycerol phosphate using glycerol kinase
- It then is oxidised to dihydroxyacetone phosphate using glycerol phosphate dehydrogenase
- This can then be converted into glyceraldehyde 3-P using triose phosphate
- Reverse glycolysis then to form glucose
What is ‘the Cori Cycle’
- Converting Lactate to glucose
- Lactate produced by anerobically respiring mucles is transferred to the liver, converted to pyruvate (by lactate dehydrogenase)
- Pyruvate then to glucose using reverse glycolysis
Amino acids cannot be stored in the cell as subunits
Hence how can amino acids be converted into glucose
(hint glucose alanine cycle)
- Alanine can move from muscle to liver
- Where it is transanimated back to pyruvate
- Pyruvate to glucose through reverse glycolysis
- Transports nitrogen from muscles to liver where it is used for urea biosynthesis
What is an α-ketoacid
An amino acid which has had its R-group removed
Apart from Alanine, how can other amino acids be metabolised
- α-ketoacids formed from glucogenic amino acids
- Enter the TCA cycle and forming oxaloacetate
- (others can form acetyl CoA in an irreversible reaction but not used to make glucose)
There are 3 reactions within glycolysis which are irreversible (high -ΔG) values
How it this combated in gluconeogenesis
Overcome by 4 gluconeogenic enzymes
The reaction forming pyruvate from phosphophenolpyruvate is irriversible
How it this overcome
- Two enzymes pyruvate carboxylase and PEPCK are used
- Pyruvate carboxylase needs a Co-enzyme in the form of biotin bound to a lysine residue, which forms a flexible arm
Where do we consider the start of gluconeogenesis to occur
In the mitocondria
How does pyruvate carboxylate operate to form oxaloacetate from pyruvate
Knowing the process of the TCA cycle, what compound could encorage this process
Pyruvate carboxylate will bind to carbon dioxide, and utilising a phosphate group from ATP
This CO₂ molecule is added onto pyruvate
Lots of Actyl CoA could encourage this process
Once oxaloacetate is formed using pyruvate carboxylate, what happens next
- PEPCK catalyses the next reaction
- Catalyses the decarboxylation and phosphorlation (using GTP) of oxaloacetate
- This will form phosphoenolpyruvate
As said before these gluconeogensis reactions occur in the mitocondria
Oxaloacetate must be transported from the mitocondria to the cytosol where PEPCK is
How does this occur
- Malate-Asparate Shuttle
- Route 2: Malate dehydrogenase (along with NADH) will convert oxaloacetate to Malate. This can be transferred across the membrane into the cytosol. Here it is re-oxidised to oxaloacetate using the same enzyme and NAD⁺
- This route is preferred due to NADH being formed in the cytosol which is needed for gluconeogenesis
From phosphenolpyruvate to fructose-1,6-bisphosphate, the glycolysis reactions (5) work in reverse
From fructose-1,6-bisphosphate to Fructose-6-phosphate, this reaction is irreversible
How is this overcome
- Fructose-1,6-phosphate is hydrolysed by fructose bis-phosphatase using water
- This forms Fructose-6-phosphate
- Releases inorganic Pi
- Key regulatory step, halted with large amout of AMP AND high levels of glucagon
Fructose-6-phosphate is converted into glucose-6-phosphate through a revesible reaction
From glucose-6-phosphate to glucose, the reaction is irreversible
How is this overcome
- Glucose-6-phosphatase (only present in liver and kidney)
- Forms glucose in a hydrolysis reaction using water
- Releases an inorganic Pi
What is the name of a diease where glucose-6-phosphatase is deficient which can cause hypoglycemia
Type 1a glycogen storage disease
What is the energy cost of forming glucose
6 ATP
2 NADH
What are 3 ways gluconeogenesis can be regulated
- Glucogenic substrates
- Enzyme synthesis
- Glucagon
Describe the structure of glycogen
A polymer of A-glucose (1,4 glycosidic bonds)
with a highly branched structure (1,6 glycosidic bonds)
Where are the main stores of glycogen found
In skeletal muscles and liver
What is the benefit of storing glucose as glycogen in a cell
Reduces the osmotic pressure on the cell
What does glycogen have to aid in its breakdown
It will have a non-reducing end on every branch
The enzymes which break down glycogen, all work on the non-reducing end
Glycogen degradation is not a reversal of synthetic reactions. Separate cytosolic enzymes are required
What are they
- Glycogen phosphorylase
- Glycogen debranching enzyme
- Phosphoglucomutase
How does glycogen phosphorylase work
- Cleaver the α(1,4) bond forming glucose-1-phosphate
- This is done on the non-reducing end
On glycogen phosphorylase, there is a large gap between the binding site for glycogen and catalytic site
What effect will this have
A limit dextrin
Means there is a number of glycogen molecule that won’t be hydrolysed by the enzyme
About 5 glycogen subunit that won’t be broke down when adjacent to a branch
How can the enzyme activity of glycogen phosphorylase be altered
Allosteric interaction and covalent modification
Inhibitors: ATP, G6P, glucose
What enzyme is used to combat the issue of the limit dextrin strand
Glycogen debranching enzyme
Acts as a α(1,4) transglycosylase: moves trisaccharide units to non-reducing branch end
AND removes the one remaining glycogen reside at the branch point to create free-glucose
What is the use of phosphoglucomutase in glycogen breakdown
Converts glucose-1-phosphate into glucose-6-phosphate
This can the continue along the glycolytic pathway and hydrolysed to glucose/ or other metabolic reactions
Starting with glucose-6-phosphate, how would you form glycogen
- Start off by forming glucose-1-phosphate in an isomerisation reaction using phosphoglucomutase
- It is activated by adding a phosphate group to form UDP-glucose using UDP-glucose pyrophosphorylase
- Glycogenin places around 7 UDP-glycose molecules on itself which allows glycogen synthase to add UDP-glucose onto the non-reducing end of glycogen
How are branches formed on glycogen
- Using a branching enzyme (4,6 transferase)
- It takes a section of the main chain and remove it, and create an α(1,6) bond
When does glycogen synthesis occur
Accekerates after a meal - well fed state
