Metabolism 4 Flashcards
How is glycolysis in the liver affected by glucagon and epinephrine?
Glucagon and epinephrine shut down glycolysis in the liver, so that glucose is preserved.
What hormones promote gluconeogenesis?
What is the first step?
Glucagon and epinephrine promote gluconeogenesis, and they increase the transcription
and synthesis of the key enzymes of gluconeogenesis.
Both of them will promote the degradation of glycogen in the liver, so that glucose-6-
phosphate is generated.
Glucose homeostatis requires two pathways. Where do they take place? Describe both.
- gluconeogenesis
- glycogen degradation
(both are highly regulated and highly active in the liver)
Describe gluconeogenesis.
What is its purpose?
What substrates are used?
How many ATP required?
essential for survival of humans and animals
helps maintain normal blood glucose levels
Results in synthesis of glucose from non carbohydrate carbon substrates like pyruvate, lactate, glycerol, glucogenic aa
-Requires 6 ATP’s.
Describe the first step of gluconeogenesis.
Note: Non-carbohydrate precursors are first converted to glucose 6-phosphate.
Glucose 6-phosphatase enzyme releases the phosphate from glucose 6-phosphate
generated by BOTH pathways (gluconeogenesis & glycogen degradation).
What would occur if there was a lack of glucose 6- phosphatase?
Glucose 6-phosphatase enzyme releases the phosphate from glucose 6-phosphate
generated by BOTH pathways (gluconeogenesis & glycogen degradation).
- Remember, phosphorylated sugars are trapped.
- W/o this enzyme, gluconeogenesis and glycogen degradation cannot
occur.
- If you have a defect in this enzyme, you cannot maintain normal blood
glucose levels without eating for long periods of time.
What will stimulate gluconeogenesis? (Hormone/conditions)
Low blood sugar (hypoglycemia) stimulates gluconeogenesis through the hormone glucagon (glucagon is increased in these conditions).
- Takes place mainly in the liver and to some extent in the kidney.
- Glycolytic flux is decreased.
- In other words, gluconeogenesis and glycolysis are reciprocally
regulated.
Gluconeogenesis is activated after …
dietary glucose has been oxidized
glycogen has been used up
How is pyruvate converted to phosphoenolpyruvate?
2 step process via oxaloacetate.
Oxaloacetate can be viewed as an “activated” form of pyruvate.
- Bicarbonate and the cofactor biotin are involved in this activation,
which requires the expenditure of ATP.
Describe the relative changes in the levels of blood glucose, hepatic glycogen, and other fuels (fatty acids and ketone bodies) during a 24-hour fast, and relative changes in hormone levels.
p 4
insulin drops
glucagon rises
free fatty acids and blood ketone bodies shoot up
liver glycogen drops a lot
blood glucose drops some
Describe what happens to glucose right after eating vs after some time.
Right after eating:
- Blood glucose levels are at their highest.
- Glucose molecules are transported into the liver through the GLUT-2 transporter.
- “ “ into skeletal muscle/heart muscle/adipose tissue using GLUT-4.
- Insulin will also be at its highest level.
- Remember: elevated blood glucose is a key stimulus for the release of
insulin.
After Some Time..
- Blood glucose levels start to increase, along with insulin levels .
Remember! The brain has an absolute requirement for glucose. It cannot metabolize fatty
acids, so it needs glucose to generate ATP, and it needs ATP to establish ion gradients!
Compare exogenous glucose, glycogen, and gluconeogenesis on a graph that compares time phases of glucose homeostasis.
Phase I (0-4 hours) Phase II (6-16 hours) Phase III (16- 28 hours) Phase IV (1- 16 days) Phase V (17-32 days)
Slide 11
P5
See chart p 6
Phase I- exogenous glucose, all tissues use glucose, glucose used by brain
Phase II- use glycogen and hepatic gluconeogensis, all tissues use glucose except liver, muscle and adipose tissue all diminished rates
Phase III- use hepatic gluconeogensis and glycogen, all tissues use glucose except liver, muscle and adipose tissue at rates between II and IV
Phase IV- gluconeogenesis hepatic and renal, brain, RBC renal medulla and small amt muscle use glucose, fuel for brain is glucose and ketone bodies
Phase V- gluconeogenesis hepatic and renal, brain uses glucose at diminished rate, RBCs, renal medulla, fuel for brain is ketone bodies and glucose
When does brain start to generate ketone bodies?
After three or four days of starvation, the body will start generating ketone bodies levels that are
high enough that they can enter the brain. The transport of ketone bodies is also up-regulated to
move the ketone bodies into the brain.
Describe the lens of the eye and its glucose needs.
The lens of the eye also can only metabolize glucose. It does not have mitochondria for the citric
acid cycle.
During starvation, about when would you run out of glycogen stores?
about a day ( I think)
phase 3
What are the major gluconeogenic precursors? Describe.
The major gluconeogenic precursors include lactate, glucogenic amino
acids, and glycerol.
Lactate – general metabolism, RBC metabolism, and muscle metabolism.
Glucogenic amino acids (e.g., alanine) – overnight degradation of muscle amino acids.
Glycerol – degradation of adipose tissue; triacyglycerols
Note: Fatty acids with an even number of carbons DO NOT contribute to a
net synthesis of glucose. Most fatty acids have an even number of carbons.
Fatty acids with an even or odd number of carbons contribute to net synthesis of glucose
ODD
Fatty acids with an even number of carbons DO NOT contribute to a
net synthesis of glucose. Most fatty acids have an even number ofcarbons.
