Metabolism: Gluconeogenesis Flashcards
What is the most important enzyme in glucose homeostasis?
glucose-6-phosphatase
only found in the liver
required for both glycogenolysis and gluconeogenesis
List the 5 stages of glucose homeostasis.
- exogenous glucose
- glycogenolysis (requires less time than fatty acid oxidation; the more stores the better)
- starting gluconeogenesis
- gluconeogenesis
- gluconeogenesis - but brain is running on ketone bodies
What are the major gluconeogenic precursors?
pyruvate
lactate
glucogenic AAs
glycerol
How much energy is required for gluconeogenesis?
6 ATP if Cori Cycle (lactate)
10 ATP if Alanine Cycle (alanine)
What activates gluconeogenesis?
- hypoglycemia (exogenous glucose has been oxidized)
- lack of glycogen stores
- glucagon/epinephrine
- low NADH
Describe the Cori Cycle.
- lactate produced by RBC and skeletal muscle metabolism
- converted to pyruvate in the liver via LDH
- 2 lactate => 1 glucose
- glucose released into circulation for cells who need more
- requires 6 ATP
Describe the Alanine Cycle.
- alanine produced from skeletal muscle protein metabolism
- converted to glucose in the liver
- 2 alanine => 1 glucose
- requires 10 ATP (4 extra ATP because must convert NH3 to urea)
How does alanine differ from aspartate in gluconeogenesis?
alanine is converted to pyruvate
asparatate is directly converted to OAA (1 less step)
Describe how glycerol contributes to gluconeogenesis.
- glycerol is the product of TAG breakdown
2. becomes DHAP
What are alternative sources of glucose?
- fructose undergoes fructolysis (F => F1P => GAP/DHAP)
- galactose gets converted to glucose (gal => G6P)
Why is PEP carboxykinase important at birth?
- not active at birth, requires a few hours to induce
- until then, baby can be hypoglycemic because can’t create PEP to enter gluconeogenesis
What is the mechanism of glycerol entering gluconeogenesis?
- glycerol => glycerol-3-phosphate (glycerol kinase, ATP)
- glycerol-3-phosphate => DHAP (glycerol-3-phosphate dehydrogenase)
NOTE: some glycerol-3-phosphate goes on to make fatty acids - yields 1/2 glucose and 1 lactate
Can you use acetyl-CoA to make glucose?
No, because it is determined to go into TCA or fatty acid synthesis
What is the mechanism of propionate entering gluconeogenesis?
- odd-chained fatty acid beta oxidation yields propionyl-CoA
- converted to OAA
- yields 1/2 glucose and 1 lactate
What are the 4 regulatory enzymes for gluconeogenesis?
- mitochondrial pyruvate carboxylase
- cytoplasmic PEP carboxykinase
- cytoplasmic F16BPase
- cytoplasmic G6Pase
Describe the reaction carried out by pyruvate carboxylase.
- converts pyruvate to OAA
- only occurs in the mitochondria
- OAA is then converted to malate to be transported to the cytoplasm, where it is remade into OAA
- requires: biotin and ATP
What are the symptoms and associated manifestations of pyruvate carboxylase deficiency?
Symptoms
- failure to thrive
- developmental delays
- recurrent seizures
- metabolic acidosis
Manifestations
- accumulation of lactate and alanine b/c can’t convert pyruvate
- prevents gluconeogenesis
Describe the reaction carried out by PEPCK
- converts OAA to PEP
- requires GTP
Describe the reaction carried out by F16BPase
- converts F16BP to F6P
Describe the relationship between PFK1 and F16Bpase.
- recall that glycolysis and gluconeogenesis are reciprocally regulated
- PFK1 is activated by F26BP => promotes glycolysis
- hence, F26BP will inhibit gluconeogenesis by inhibited F16BPase
Describe the reaction carried out by G6Pase.
- converts G6P to Glucose
- occurs in the liver; both glycogenolysis and gluconeogenesis require it
Where is G6Pase found?
- lumen of the ER in liver, kidney, and intestinal cells
How does G6Pase work?
- G6P enters the ER via ubiquitinous transporter
- G6Pase converts to glucose and Pi
- exits lumen via transporters
Describe the symptoms and etiology of von Gierke disease. What are some other names for it?
- glycogen storage disease type 1 (G6Pase deficiency)
- accumulation of glycogen in the liver, but can’t break it down to make glucose
- poor tolerance of fasting
- growth retardation
- hepatomegaly
- prevents gluconeogenesis and glycogenolysis
