Week 5: Gluconeogenesis Flashcards
What are primary pathways of anabolic carbohydrate metabolism?
Gluconeogenesis
Pentose Phosphate Pathway
Glycogen Degradation and Synthesis
What is gluconeogenesis
Making new glucose and the synthesis of glucose from non-carbohydrate precursors
What are the major precursors of gluconeogenesis?
Lactate, glucogenic amino acids, and glycerol
Is gluconeogenesis the reversal of glycolysis?
No
What is the site of gluconeogenesis?
Liver
What is the purpose for gluconeogenesis?
Used to maintain blood glucose levels in order to provide glucose to the brain and red blood cells
What are the differences between glycolysis and gluconeogenesis?
- Both thermodynamically favorable
- Exergonic
- Reversible reactions are used by both pathways
- Irreversible reactions of glycolysis must be bypassed in gluconeogenesis
What steps of glycolysis are irreversible?
1, 3, 10
What occurs when pyruvate is converted back to PEP?
1 . Pyruvate + HCO3 + ATP by pyruvate carboxylase and biotin to form oxaloacetate
2. Oxaloacetate is decarboxylated and phosphorylated by GTP and PEP carboxylkinase to produce PEP and CO2
How does oxaloacetate cross the mitochondrial membrane?
It is reduced to malate
What enzyme oxidizes malate back to oxaloacetate?
Malate dehydrogenase
Where in the body is lactic acid produced?
Muscle
How would glycerol enter gluconeogenesis and glycolysis?
- Glyceral fueled by ATP and glycerol kinase in converted to glycerol phosphate
- Glycerol phosphate is dehydrated by NAD+ and glycerol phosphate dehydrogenase to form dihydroxyacetone phosphate
How is F-1,6BP converted to F-6P
Through F-1,6 bisphosphatase
What are the important regulatory steps for the conversion of F-1,6BP to F-6P?
- Inhibited by AMP (energy-poor state)
2. Activated by high levels of ATP
What situations allow generation of glucose when glycogen stores are depleted?
- during fasting and starvation
- during vigorous exercise (cori cycle brings lactate from muscles)
- can generate glucose from amino acids, glycerol, and lactate
What is reciprocal regulation?
Glycolysis will predominate when glucose is abundant, and gluconeogenesis will be highly active when glucose is low.
Where does pentose phosphate pathway occur?
Cytoplasm
What are the main products of Pentose Phosphate Pathway?
2 NADPH and ribose 5-phosphate
What is NADPH used for in the Pentose Phosphate Pathway?
- Used for reductive biosynthesis of fatty acids and steroids
- Repairs oxidative damage
What is ribose-5-phosphate used for in the Pentose Phosphate Pathway?
- Used in DNA and RNA synthesis
2. Synthesis of some coenzymes (NADH, FADH2, coenzyme A) and ATP
What synthesis reactions would use NADPH?
- Fatty acid biosynthesis
- Cholesterol biosynthesis
- Neurotransmitter biosynthesis
- Nucleotide biosynthesis
What detoxification reactions would use NADPH?
- Neutralizes reactive oxygen species
2. Reduction of glutathione
What makes NADPH a strong reductant?
- Has the same reduction potential as NAD+ NADH redox pair
- Accepts 2e- in the form of a hydride ion (:H-) and releases a proton.
- Differs from NAD+ by phosphorylated ribose
What does the oxidative phase of the Pentose Phosphate Pathway do?
Produces NADPH and Ribulose-5-phosphate
What does the non-oxidative phase of the Pentose Phosphate Pathway do?
- Interconverts C3, C4, C5, C6, and C7 sugars in to sugar phosphates
- Reversible
What 3 metabolic states must be met during the flux between the oxidative and reductive phases?
- If increased NADPH is required
- If nucleotide pools need to be replenished
- If ATP levels are low
What occurs when NADPH levels are high?
- NAPDH competes with NADP+ for binding to G6PD resulting in lower enzyme activity
- Increased flux of Glucose-6-P through glycolysis
