Gluconeogenesis & Alcohol Metabolism

Question 1

Which organs can perform gluconeogenesis?

Answer 1

• the liver is the MAJOR organ

- in times of prolonged starvation, however, the kidneys also perform some gluconeogenesis

Question 2

What are the three irreversible steps of glycolysis that must be bypassed in gluconeogenesis?

Answer 2

• glucose to G6P via hexokinase/glucokinase
• F6P to F-1,6-BP via PFK-1
• PEP to pyruvate via pyruvate kinase

Question 3

What are the three major sources of carbon used to make glucose via gluconeogenesis? What part of the cycle do they enter?

Answer 3

• pyruvate / lactate; the two are isoforms via LDH
• alanine: comes from protein breakdown; becomes pyruvate
• glycerol: comes from triglyceride breakdown; becomes DHAP –> F-1,6-BP
• (odd-numbered FAs are also a source, but are a VERY small source; propionyl-CoA becomes succinyl-CoA, which becomes oxaloacetate)
• (glycogen does not count as it is broken DOWN into glucose in glyogenolysis)

Question 4

Alanine comes from protein breakdown - how many amino acids are glucogenic?

Answer 4

• 18 amino acids are glucogenic (meaning they can be made into gluocse)
• only 2, lyseine and leucine, are strictly ketogenic amino acids (meaning they can only make ketone bodies)

Question 5

What is the site of gluconeogenesis?

Answer 5

• in both the mitochondria and cytoplasm
• pyrvuate must enter the mitochondria to become oxaloacetate, which is then shuttled back into the cytoplasm to form phosphoenolpyruvate

Question 6

Which enzyme converts pyruvate into oxaloacetate? What does it require? What regulates it?

Answer 6

• (remember this occurs in the mitochondria)
• pyruvate carboxylase adds a CO2 onto pyruvate to form oxaloacetate
• pyruvate carboxylase is an “ABC” enzyme: requires, ATP, biotin (B7), and CO2
• pyruvate carboxylase is activated by acteyl-CoA

Question 7

Which enzyme converts oxaloacetate into PEP? What does it require? What regulates it?

Answer 7

• (remember this occurs in the cytoplasm)
• phosphoenolpyruvate carboxykinase generates PEP + CO2 from oxaloacetate
• requires GTP
• is hormonally activated at the genetic level by glucagon and cortisol (genetic responses are slower)

Question 8

Which enzyme converts fructose-1,6-bisphosphate into fructose-6-phosphate? What is it regulated by?

Answer 8

• fructose-1,6-bisphosphatase (F-1,6-BPase)
• generates F6P and an inorganic phosphate
• activated by ATP and acteyl-CoA
• deactivated by F-2,6-BP and AMP

Question 9

Explain how fructose-2,6-bisphosphate and ATP regulate both glycolysis and gluconeogenesis.

Answer 9

• F-2,6-BP activates PFK-1 and inhibits F-1,6-BPase

- ATP activates F-1,6-BPase and inhibits PFK-1

Question 10

What is the rate-determining enzyme of gluconeogenesis?

Answer 10

• fructose-1,6-bisphosphatase

Question 11

Which steps require energy for gluconeogensis? Where is this energy coming from since we’re in a starved state?

Answer 11

• pyruvate into oxaloacetate requires ATP (and acetyl-CoA)
• oxaloacetate into PEP requires GTP
• F-1,6-BP into F6P requires ATP and acetyl-CoA for the enzyme to function
• this energy (and acetyl-CoA) is coming from the B-oxidation of fatty acids

Question 12

What enzyme converts glucose-6-phosphate into glucose?

Answer 12

• glucose-6-phosphatase