Lecture 32 - Coordinating Metabolism: Fuel Storage Flashcards
Why do we need fuel stores?
Because we can’t store ATP or transfer it to other tissues, it must be made in the cell requiring it at the time by oxidizing fuels
What is glucose stored as?
glycogen in liver and muscle
What are fatty acids stored as?
triacylglycerol droplets in adipose
Is there a protein store?
No
When may stored energy be required
between meals, overnight, for activity i.e. exercise
What is required to maintain glucose levels?
Fuel stores
How do we survive prolonged fasting or starvation?
With fuel stores
What is the energy equivalent in 15kg of TAG?
590000kJ
What can the liver NOT use for fuel?
Ketones
What fuels can muscles use?
All fuels
What can’t the brain use for fuel?
Fatty acids
Why can’t the brain use fatty acids?
They can’t cross the blood brain barrier (BBB)
What can’t RBCs use for fuel?
Fatty acids
Why can’t RBCs use fatty acids?
Because they don’t have mitochondria
What is adipose specialised in?
Storing and mobilising fats
Is there a limit on the amount of fat you store?
No unlimited
What are excess TAGs and glucose from diet converted to?
stored fat
What is TAG synthesis in adipocytes driven by?
Insulin
What things does insulin do to a adipocyte?
- Promotes glucose uptake via GLUT4
- Stimulates LPL
- Stimulates glycolysis via hexokinase
- Stimulates DNL
What does glucose provide to an adipocyte?
Glycerol-phosphate backbone, and provides acetyl-CoA for de novo lipogenesis (DNL)
What allows glucose uptake by adipose?
GLUT4
What allows glucose uptake by Liver?
GLUT2
Is GLUT 2 stimulated by insulin?
No
Is GLUT 4 stimulated by insulin?
Yes
What is dietary fat packaged into?
Chylomicrons
What is glucose metabolised to in adipocytes?
Glycerol-3-Phosphate, and then used as the backbone for TAG synthesis
What does stimulation of lipoprotein lipase (LPL) by insulin do?
hydrolyses TAGs to release FA into tissues where they are resynthesized into TAGs
What happens when glucose undergoes glycolysis in the liver?
Glucose undergoes glycolysis generating excess acetyl-CoA that can be synthesised into FAs via the FA synthase complex, then into TAGs, and packaged into VLDL particles
How is excess glucose carbon converted to fatty acids?
Via acetyl CoA
Where does the conversion of Glucose to Fatty acids take place?
Mainly in the liver but also in adipose
Does it require energy to convert Glucose to fatty acids
Yes
How are fatty acids exported?
As TAGS in VLDL
How are fatty acids delivered to adipose?
Via LPL activity and stored as TAGs
What overall stimulates the conversation of glucose to fatty acids?
Insulin
What is glycogen?
A branched polysaccharide
Where is glycogen stored ?
In the liver and muscle
Where may you find glycogen in the cell?
As granules in the cytoplasm
What type of bonds are in glycogen?
1-4 and,1-6 glycosidic bonds
What happens during glycogen synthesis?
Glucose is trapped in cell, and diverts from glycolysis
What is the starting substrate in the glycogen synthase reaction?
UDP-Glucose (UDP-G).
What happens to UDP in the glycogen synthase reaction?
It is released from UDP-Glucose, leaving the glucose unit to attach to the glycogen chain.
What intermediate is formed during the glycogen synthase reaction?
Oxonium ion intermediate.
What bond is formed when a glucose unit is added to glycogen?
A new glycosidic bond (α(1→4)).
What is the enzyme responsible for catalyzing the glycogen synthase reaction?
Glycogen synthase.
What happens to the glycogen chain after the reaction?
It grows by one glucose unit, forming glycogen with “n+1 residues.”
What is released during the formation of the glycosidic bond?
A hydrogen ion (H+).
What does stimulation of the insulin signalling pathway activate?
PKB (aka AKT), also activate a phosphatase (PP1)
WHat does PKB activation do?
Inactivates glycogen synthase kinase (GSK3)
What does GSK3 inactivation do?
Prevents glycogen synthase from being phosphorylated which keeps it active
What does activation of phosphatase (PP1) do?
Dephosphorylates glycogen synthase which also helps to keep it active
What enzyme is responsible for introducing branches in glycogen?
Branching enzyme.
What happens to the glycogen chain after branching occurs?
Both branching chains can grow
When and where does glycogen synthesis occur?
In liver and muscle immediately after a meal
What energy inputs does glycogen synthesis require?
ATP and UTP
What stimulates glycogen synthesis?
Insulin
What enzymes are required for Glycogen synthesis?
Glycogen synthase, and branching enzyme
What is the high energy precursor that glycogen is made from?
UDP-Glucose
What happens to excess glucose that isn’t converted to glycogen?
Converted to acetyl-CoA and then into fatty acids by the FA synthase complex in liver
What is liver glycogen important for?
Maintaining blood glucose levels
How big are glycogen granules?
0.1 µm
How big are mitochondria?
10 µm
Where can muscle glycogen be used?
Only within muscle
Why can muscle glycogen only be used within muscle?
Muscle cells are missing glucose-6 phosphotase
What can help enhance glycogen stores?
Carb loading
What benefits does carb loading have?
- Has been shown to be beneficial for endurance athletes
- Prolongs time to fatigue and protects against exercise-induced hypoglycaemia
What are glycogen storage diseases?
Inherited metabolic disorders involving a deficiency of one of the enzymes responsible for glycogen synthesis or breakdown
What can a glycogen storage disease lead to?
an abnormal accumulation or deficiency of glycogen in liver or muscles
What are some potential symptoms from glycogen storage diseases
hypoglycemia, ketosis, muscle cramps and fatigue,
enlarged liver (hepatomegaly), growth retardation in children.
