FASTING METABOLISM

Question 1

What is always the initial energy source?

Answer 1

Glucose!!
* Liver contributes this during fasting (glycogen)

Question 2

Gluconeogenesis

Answer 2

Made from other substrates
* AA from muscle breakdown
* lactate from blood and muscle cells

Question 3

Lipolysis

Answer 3

Lipid -> fatty acid (used in some organs) glycerol (coverted to glucose in liver)

Question 4

Ketone bodies

Answer 4

Fatty acids (FA) -> ketone bodies if in blood stream for a while
* brain will slowly move to this source during fasting

Question 5

Energy stores

Answer 5

Liver - glycogen
Adipose - largest store
Skeletal Muscle - last resort

Question 6

Key hormones in fasting

Answer 6

INSULIN - secreted at HIGH glucose (made by beta cells)

GLUCAGON - secreted at LOW glucose (made by alpha cells)

Question 7

Glucagon and transcription

Answer 7

Glucagon comes from proprotein
* different peptide hormones can be extracted
* depends on which tissue it is expressed
* enzymes in alpha cells process GLUCAGON only

Question 8

GLP

Answer 8

Glucagon-like-protein
* GLP-1: secreted by intestine into blood in response to food
* GLP-2

Question 9

Glucagon induces…

Answer 9

Lipolysis
Gluconeogenesis
Glycogenolysis

Question 10

Main Glucose Source Human First 24 h of fast

Answer 10

Within 4h exogenous carbs used up
* Liver glycogen now contributes
* Gluconeogenesis takes over ~ 16h (can be maintained for a long time)
* Liver glycogen stop at ~30h

Question 11

Structure of liver glycogen stores

Answer 11

Centre is glycogenin protein
* glucose polymerised here
* many chains, high density
* breaking down linear chains is FAST but branching points SLOW

Question 12

Glycogenolysis

Answer 12

Glycogen > G-1-P > G-6-P
* In liver: transported to lumen of ER
* Phosphate chopped off > glucose
* Released via GLUT2

Question 13

how does glucagon stimulate glycogenolysis?

Answer 13

Glucagon bind cell surface receptor of hepatocyte
* signalling cascade > generate cAMP
* binds PKA > activates
* phosphorylate substrates (PYGL)

Question 14

Key Substrates for Gluconeogenesis

Answer 14

1. Alanine and Glutamine (muscle)
2. Pyruvate and Lactate (RBC)
3. Glycerol (Adipose)

Question 15

How does glucagon stimulate gluconeogenesis?

Answer 15

Need to inhibit PKA
* So we reduce allosteric modulator (F-2,6-BP) > removes inhibition of gluconeogeneis

Question 16

What regulates lipolysis?

Answer 16

regulated by glucagon and norepinephrin
* involved with PKA
* release of glycerol and FFA

Question 17

Poorer metabolic outcomes associated with what kind of fat?

Answer 17

visceral (eWAT)
* subcutaneous (psWAT) is good

Question 18

FFA can easily be used by…

Answer 18

the heart and muscles

Question 19

What are some ketone bodies?

Answer 19

1. β-hydroxybutyrate (βOHB) - MAJOR
2. Acetoacetate
3. Acetone

Question 20

How FFA is converted to ketone bodies

Answer 20

Beta-oxidation results in Acetyl-CoA
* Acetoacetate spontaneously converts to acetone
* BDH1 required for conversion to βOHB

Question 21

When do ketone bodies dramatically increase?

Answer 21

After 48h of fasting
* FA plateau
* βOHB continues to accumulate
* Brain takes a week to change over