Human metabolism lecture 3

Question 1

Glucagon

Answer 1

• 160 aa precursor made in reaction by PC2
• Hormone of starvation
• After meal glucagon ↓

Question 2

Glucagon target tissues

Answer 2

• x glucagon receptor in human adipose or skeletal

- Lots in liver

Question 3

Glucagon effect

Glycogen breakdown + glycogen synthesis

Answer 3

• Target of PKA = phosphorylase kinase b + GS
• GS phosph on site 2
• Difference liver vs muscle = site 1a+b is only in muscle, 2 is in both
• Protein phosphatase I has glycogen binding unit (G)
• Gl lacks PKA phosph site
• Phosphorylase a binds GL x Gm
• Adrenaline → PKA → GM of PPI phosph → G + C disc → small inhibitor 1-P binds PPI + inactivates (x for GL)

Question 4

Glucagon effect

Glycolysis + gluconeogenesis

Answer 4

• Glycolytic E switched off, gluconeogenic on

1. PFK + F1,6BPatase
   - F2,6BP = regulator, catalysed by bifunctional E
   - Glucagon → PKA → phosph bifunctional E on Ser32 → hydrolyses F2,6BP → glycolysis loses activator
2. Pyruvate kinase (Liver)
   - Phosph by PKA (inactive)
   - Dephosph by PP1 (active)
   - Allosterically activated by F1,6BP, inactive by Ala (stimulates/inhibits phosphorylation)

Question 5

Glucagon effect

Transcription

Answer 5

CREB

• PKA → phosph CREB on Ser133 → translocates to nucleus
• dephosph of CRTC2 → translocation to nucleus, forms complex
• E.g. PEPC = ↑ glucagon, active PKA, CREB phosph, SIK2 phosph + x phosph CRTC2 so can bind CREB + CBP → transcription of gene
• 2nd wave = PGC1a

Question 6

Glucagon effect

FA synthesis + oxidation

Answer 6

• Transport of FA to mit = mediated by CPT1/2, malonyl coA inhibits CPT1
• Active ACC = FA + malonyl coA made, FA ox inhibited
• Glucagon phosph + inhibits ACC in liver
• AMPK phosph + inhibits ACC
• 2 isofordms ACC2/ACC1

Question 7

Liver metabolism branch points

Answer 7

• Acetyl coA can be fed into TCA or HMG-coA cycle

- HMG coA synthase + citrate synthase compete for acetyl coA