Gluconeogenesis & Pentose Phosphate Pathway Flashcards
What is the purpose of gluconeogenesis? Where does it occur and what are its substrates?
Synthesize glucose, specifically during prolonged fasting
Occurs in liver and kidney
Main substrates are pyruvate, oxaloacetate, and glycerol
When is gluconeogenesis most active?
During fasting when insulin is low and glucagon is high
What cycle is gluconeogenesis also part of?
Cori Cycle - converts lactate back to glucose
Fructose 1,6 bisphosphatase deficiency
Gluconeogenesis disorder
Pt presents with fasting hypoglycemia and metabolic acidosis. Liver shows fat deposits and pt has abnormal glucagon response, elevated serum lactate, pyruvate, and alanine during hypoglycemia
What general symptoms do patients with a gluconeogenesis disorder present with? Why?
- Fasting hypoglycemia - impaired glucose production
- Metabolic acidosis - accumulation of lactate, pyruvate, and amino acids
- Abnormal glucagon response - no sign. increase in blood glucose
- Liver stores fat, not carbs - Turns lactate, pyruvate into fatty acids instead of glucose
What are the four reactions unique to gluconeogenesis?
- 2 Pyruvate to 2 Oxaloacetate via Pyruvate Carboxylase
- 2 Oxaloacetate to 2 PEP via PEP carboxykinase
- Fructose 1,6-bisphosphate to Fructose 6-phophate/Glucose 6-phosphate via Fructose 1,6 bisphosphatase
- Glucose 6-phosphate to glucose via glucose 6-phosphatase
Is gluconeogenesis the reverse of glycolysis?
Not quite because need to bypass irreversible steps from glycolysis
What does Glucose 6-phosphatase produce for release from the cell?
Free glucose!
How much energy to make glucose from pyruvate?
6 ATP/GTP
What is the main regulated step in gluconeogenesis?
Fructose 1,6-bisphosphatase which forms glucose 6-phosphate from fructose 1,6-bisphosphate
*Responds to Fructose 2,6-bisphosphate
What inhibits and stimulates pyruvate carboxylase?
Inhibited by - Insulin
Stimulated by - Acetyl-CoA
What inhibits and stimulates PEP carboxykinase?
Inhibited by - Insulin, AMP
Stimulated by - Glucagon
What inhibits and stimulates fructose 1,6 bisphosphatase?
Inhibited by - Insulin via Fructose 2,6 bisphosphate, AMP
Stimulated by - Citrate
What inhibits and stimulates Glucose 6-Phosphatase?
Inhibited by - Insulin
Stimulated by - Glucagon
What is an alternate pathway for the degradation of glucose?
Pentose Phosphate Pathway or Hexose Monophosphate Shunt
What does the pentose phosphate Pathway provide?
NADPH for anabolic reactions, defense against reactive oxygen, p450 enzymes
Ribose for nucleotide synthesis
What is the pentose pathway important for red blood cells?
Only source of NADPH
How does the pentose phosphate pathway meet the needs of the cell?
Exchanges metabolites with gluconeogenesis and glycolysis.
Do so by producing fructose 6 phopshate and glyceraldehyde 3 phosphate in teh nonoxidative phase which enter glycolysis or gluconeogenesis.
What does a patient with a Pentose Phosphate Pathway Disorder present with?
Hemolytic anemia - red blood cells lack NADPH for protection against radical stress, bite cells in peripheral blood smear
Jaundice - degradation of heme released from red blood cells
Enlarged spleen - Removal of damaged RBCs from circulation
What is the regulated/committed step of Pentose Phosphate pathway?
Glucose 6 phosphate dehydrogenase converting Glucose 6-phosphate to 6-phosphogluconolactone
What two reactions in the pentose phosphate pathway produce NADPH, CO2, and ribulose 5P? What reactions are these?
Oxidation reactions
Glucose 6 phosphate dehydrogenase produced 1NADPH
6-phosphogluconate dehydrogenase produces NADPH, CO2, and ribulose 5-phosphate
What inhibits glucose 6 phosphate dehydrogenase?
NADPH
What occurs in the nonoxidative phase of pentose phosphate pathway?
Converts pentoses to fructose 6 phosphate and glyceraldehyde 3 phosphate
Glucose 6 phosphate dehydrogenase deficiency
PPP disorder
Prevalent in Mediterranean and African Americans.
X-linked - affects predominantly males
Depletes RBS of NADPH which lowers radical stress resistance and then radical stress (H2O2) causes hemolytic anemia
Describe activities of glycolysis and PPP in a fat tissue that is in fed state
Adipose tissue will want to convert glucose to fatty acids
High insulin, Glycolysis active
Glucose GP oxidized by Glucose 6P dehydrogenase in PPP
Needs NADPH and pyruvate so takes Pentoses not being used from PPP and turns them into F6P and GA3P so they can enter glycolysis
Describe activities of glycolysis and PPP in a rapidly dividing cell
High conc of unused NADPH inhibits Glucose 6P dehydrogenase and prevents production of pentose P in PPP
Lack of pentose P directs flow through non-oxidative path of PPP towards production of pentose P from G6P and GA3P
Rapidly diving cells use glycolysis and nonoxidative PPP
