Question

Regarding ATP/AMP concentrations in the cell:

a. Upon ATP hydrolysis, why might the AMP increase affect the cell more than the ATP decrease?

b. What role does AMP kinase play?

c. What pathways would be activated by high ATP/low AMP, energy producing or energy storage?

d. What pathways would be activated by low ATP/high AMP, energy producing or energy storage?

Answer 1

a)

b) AMP Kinase has several roles in cell depending on ATP/AMP concentration:

1. It phosphorylates acetyl-CoA carboxylase 1 (ACC1) or sterol regulatory element-binding protein 1c (SREBP1c) and thus inhibits ATP consuming processes such as fatty acids synthesis, cholesterol biosynthesis and also triglycerides biosynthesis. It induces fatty acid uptake and ATP producing process, β-oxidation.
2. In skeletal muscle AMPK phosphorylates Rab-GTPase-activating protein TBC1D1, which in turn stimulates fusion of GLUT4 transporter vesicles with the plasma membrane and increases glucose uptake. AMPK induces glycolysis (ATP producing) through the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase II/III and phosphorylation of glycogen phosphorylase. It inhibits glycogen synthesis (ATP requiring) also by an inhibitory phosphorylation of glycogen synthase. In hepatocytes, AMPK has an inhibitory effect in gluconeogenesis through the inhibition of certain transcription factors e.g. hepatocyte nuclear factor 4 (HNF4) and CREB regulated transcription co-activator 2 (CRTC2).
3. AMPK inhibits high energy protein biosynthesis process and direct the cell to switch from cap-dependent high energy requiring translation to cap-independent low energy requiring translation event, by phosphorylating TSC2, RPTOR, transcription initiation factor 1A.66, and eEF2K.

c) Energy storage

d) Energy producing