Lecture 31: Gluconeogenesis and the Pentose Phosphate Pathway Flashcards
27/11/24
What happens when glucose levels are low in animals?
Gluconeogenesis occurs and glucose is released from the liver
What happens when glucose levels are low in plants?
Glucose is made through a combination of PPP and gluconeogenesis
What do anabolic processes that convert glucose to pyruvate use?
ATP and GTP
How many irreversible steps does glycolysis have?
3
for reversible and irreversible steps, what does ΔG depend on?
ΔG depends on ΔGo’ and q
Reversible steps:
ΔG close to 0 so changes in q controls direction of reaction
Irreversible steps:ΔG «_space;0 so physiological changes in q not big enough to reverse reaction
Is itr true that ‘steps with large negative ΔG are irreversible under physiological conditions and hence often used as regulatory steps’?
Yes
Are reversible steps shared in 2 opposing pathways good for regulation?
No
How is glucose made in gluconeogenesis?
Glucose-6-P + H2O → Glucose + Pi
How is F-6-P made in gluconeogenesis?
F-1,6-bisP + H2O → F-6-P + Pi
why isn’t ATP regenerated in gluconeogenesis?
Because it isn’t simply a reversal of the steps in glycolysis
Futile cycles
- losing ATP
- Not really gaining anything from running the 2 cycles at the same time
- Fructose-6-P + ATP → Fructose-1,6-bisP + ADP
Fructose-1,6-bisP + H2O → Fructose-6-P + Pi
Net: ATP + H2O → ADP + Pi
(Metabolic pathways tightly regulated to avoid futile cycles
PFK and Fructose-1,6-bisphosphatase both tightly
and oppositely regulated, so that only one reaction runs at a time
)
What is the last step (irreversible) of glycolysis?
PEP + ADP → pyruvate and ATP
Draw out the structure of pyruvate
Glycolysis
Pyruvate -> Oxaloacetate -> PEP
What is the starting material for pyruvate?
Lactate
Some amino
acids
What is the starting material for Oxaloacetate?
Some amino acids
Is oxaloacetate a citric acid intermediate?
Yes
What is the starting material for Dihydroxyacetone?
Even though fats can’t normally be turned into glucose, glycerol
Where in the cell does gluconeogenesis occur?
In the cytosol (cytoplasm)
Is gluconeogenesis a linear or branched pathway?
Linear
What are the entry points for gluconeogenesis?
Pyruvate, oxaloacetate, glyceraldehyde-3P
What is the end point of gluconeogenesis?
Glucose
What other pathway is gluconeogenesis linked to?
Pentose phosphate pathway and others
How many steps does gluconeogenesis have?
11 steps, most shared with glycolysis
How is gluconeogenesis regulated?
Oppositely to glycolysis
Apart from pyruvate, what can also generate acetyl coA?
Fatty acids and ketogenic amino acids
Can glucose be metabolised into ribose?
Yes
Does NADPH have any relevance in ATP regeneration?
No
What is NADP essential fr?
reductive biosynthesis and reducing oxidative stress (antioxidant)
Does NAD help make ATP?
Yes
Do NAD and NADP have opposite roles?
Yes
What is the Pentose phosphate pathway?
The sequence of reactions that converts glucose to pentoses (then to hexoses and trioses) with the production of NADPH
What is the pentose Ribose-5-P needed for?
Ribose-5-P needed for DNA and RNA (and ATP, NAD+, FAD, CoA) synthesis
What are the 2 main functions of the pentose phosphate pathway?
Producing NADP and producing Ribose-5-Phosphate
What are the 2 different stages of the pentose phosphate pathway?
- The oxidative stage, where the NADPH is being generated.
- The non-oxidative stage, where ribose-5-P and glycolytic intermediates are generated.
Draw out a diagram of the pentose phosphate pathway
Describe the oxidative steps of the pentose phosphate pathway
- Glucose 6-P → Ribulose 5-P + CO2
- Strategy: oxidise glucose, then oxidatively decarboxylate. NADP+ is the electron acceptor for both steps
- Step 1: Glucose 6-P Dehydrogenase
oxidises to an intramolecular ester
forms NADPH
control step - Step 2: Gluconolactonase
hydrolyses intramolecular ester. From ring structure to chain carboxylic acid. - Step 3: 6-P gluconate DH
oxidatively decarboxylates releasing CO2.
forms NADPH. G-6-P to ribulose-5-P giving 2 NAPDH
Non oxidative stage
- Ribulose 5-P → Ribose 5-P
- Via a ketose - aldose isomerisation (Similar to G-6-P/F-6-P interconversion in glycolysis
) - Ribose can be removed and used to make DNA/RNA OR Ribulose can be recycled to glucose
-
Carbohydrate interconversions to form G-6-P
3 Ribulose-5-P → 2 F-6-P + 1 G-3-P → (2.5) G-6-P
Gluconeogeneis can then be used to regenerate glucose
These reactions are reversible i.e. controlled by availability of substrates
What type of pathway is the pentose phosphate pathway?
A cyclic pathway
Describe the 4 different modes of the pnetose phosphate pathway
No NADPH production, G-6-P converted to ribose (when no reductive biosyntheiss needed i.e n fatyy acids needed)
Production of both NADPH and ribose
NADPH needed but no ribose
Cells need NADPH and ATP
Describe mode 1
- Maximises ribose-5-P production
- Occurs in rapidly dividing cells that need lots of DNA and RNA
- Carbohydrate interconversions (in reverse)
- Non-oxidative stage run backwards
- Starts from glycolytic intermediates
- No oxidative stage , Hence, no NADPH production
Describe mode 2
- Cells need both ribose-5-P and NADH
- Can occur in most cells under appropriate physiological conditions
- G-6-P is converted to R-5-P
- Only oxidative stage is running
- 2 NADPH per glucose
Describe mode 3
- NADPH is needed but not ribose-5-P
- Occurs in adipose tissue or red blood cells
- G-6-P is completely oxidised to CO2
- Cyclic mode
- 12 NADPH per glucose
Describe mode 4
- Cells need NADPH and ATP
- Occurs in most cells under appropriate physiological conditions
- Like Mode 3, but glycolytic intermediates are used for energy production, not in gluconeogenesis
Favism
Recessive X-linked disorder
Causes Hemolytic anemia when eating fava beans and sometimes other legumes
Hemolytic anemia will also be seen when they take other types of drugs
Hemolytic anemia is when the red blood cells burst
This is due to Glucose-6-P dehydrogenase deficiency, i.e. the PPP
pathway is compromised
Favism compromises NADPH but not ribose-5-P production via mode 1
NADPH reduces oxidative stress
Red blood cells dependent on PPP to reduce oxidative stress
Red blood cells exposed to oxidative stress are prone to hemolysis
Deficiency is benign when no oxidative stress
Which enzyme catalyses the first step in the pentose phosphate pathway? (key regulatory enzyme for oxidative stage)
Glucose-6-P dehydrogenase / oxidative stage
is it possible to convert fatty acids into glucose?
No
Despite it seeming counterintuitive gluconeogenesis does take place during intense exercise. Why would an organism synthesize glucose and at the same time
use glucose to generate energy?
is a good example of interorgan cooperation in higher organisms. When muscle is
actively contracting, lactate is produced from glucose by glycolysis. The
lactate is released into the bloodstream and absorbed by the liver, where it is
converted by gluconeogenesis into glucose (the Cori cycle). The newly
synthesised glucose is then released and taken up by the muscle for energy
generation.
what do pentoses include?
Ribose-5-P needed for DNA and RNA (and ATP, NAD+, FAD, CoA) synthesis
