Metabolic Cycle Regulation

Question 1

Describe the major energetic reactions of glycolysis

Answer 1

glucose —(hexokinase)—> G-6-P
F-6-P –(phosphofructokinase)–>F-1,6-bisphosphate
PEP –(pyruvate kinase)–> pyruvate

Question 2

Explain why hepatocytes express an additional hexokinase isozyme

Answer 2

glucokinase works at a lower Km; captures more glucose –> store glycogen and make fat
by insulin increasing glucokinase – keep more glucose

Question 3

Identify how glycolysis versus gluconeogenesis is regulated in hepatocytes

Answer 3

in glycolysis, processes are stimulated based on the regular cellular regulations and also negates gluconeogenesis processes
in gluconeogenesis, glucagon slows glycolysis and fatty acid synthesis and speeds up gluconeogenesis and glycogenolysis

Question 4

Describe the importance of insulin and non-insulin dependent glucose transporters

Answer 4

insulin-independent is for all cells and allows glucose to be taken up at a baseline; insulin-dependent allows certain tissues (heart, skeletal muscle, and adipose and liver) to take up extra glucose

Question 5

Explain the modulation of activity through the Krebs cycle by specific molecules

Answer 5

pyruvate –> acetyl CoA: high cell energy level inhibits reaction by phosphorylating pyruvate dehydrogenase, high FADH2, NADH inhibits; low cell energy activates, Ca2+ (in muscle) activates
OAA –> citrate: high succinyl CoA inhibits, high ATP, FADH2, NADH inhibits
Isocitrate —> alpha-ketoglutarate: high succinyl CoA inhibits, high ATP, FAD2, NADH inhibits, Ca2+ (in muscle) activates
alpha-ketoglutarate —> succinyl CoA, high ATP, FADH2, NADH inhibits, Ca2+ (in muscle) activates

Question 6

Explain why hepatic pyruvate carboxylase should be active in both fed and fasted states

Answer 6

?

Question 7

Identify the effect of hormones, insulin, glucagon and ephinephrine on target metabolic pathways and respective enzyme activities

Answer 7

hormones:
insulin:
glucagon:
epinephrine:

Question 8

Describe the central role of AMP-activated protein kinase in cellular metabolism

Answer 8

?

Question 9

What does insulin stimulate in muscle cells?

Answer 9

GLUT 4 (for glycogen synthesis)
PFK-2 (which stimulates the rest of the pathway)
Pyruvate dehydrogenase (by dephosphorylating the phosphorylated pyruvate dehydrogenase)
Glycogen synthase

Question 10

What does insulin stimulate in adipose tissue?

Answer 10

GLUT 4 (for fatty acid synthesis)
Acetyl CoA carboxylase (for malonyl and palmotoyl CoA synthesis)

Question 11

What affects acetyl CoA carboxylase?

Answer 11

increased citrate -stimulates
insulin - stimulates
increased palmotoyl CoA - inhibits (keep pace)

Question 12

What does glucagon do to hepatocytes?

Answer 12

reverse PFK II -stimulate FBPase II (inhibit PFK I)
directly inhibit PFK I and pyruvate kinase
EVEN WITH LOW ENERGY CONDITIONS
PEPCK stimulated
increases transcription of G-6-phosphatase, PEP carboxylase, and Pyruvate carboxylase
stimulate breakdown of glycogen
stop fatty acid synthesis

Question 13

What does glucagon do to skeletal muscle?

Answer 13

NOTHING

Question 14

What does glucagon do to adipose tissue?

Answer 14

stimulate PEPCK to produce glycerol-3-p and make TAGs (but then break down as long as glucagon is around)
stop fatty acid synthesis