Early Starvation Flashcards
Starvation begins at the end of the ______ period. What does this mean?
Postabsorptive period. All the food is digested and no substances are coming in from the gut.
During starvation, the body becomes reliant on ____ and _____.
Blood and stored fuels.
What do we store a lot of energy as but not use as a source of energy in starvation? Why?
Protein. There is a limit to how much of it we can break down before we die.
Keep blood glucose at ____mM. Known as ______.
5mM. Euglycemia.
The brain can only use what as fuel under normal circumstances? How much does it use?
Glucose. 120g a day.
Why cant the brain use FA?
Cant cross the blood-brain barrier
How is the main energy source of the brain transported in?
GLUT-1 transporters.
We store most of our energy as _____. But it cant be converted into _______. Why?
Fat. Carbohydrates. Pyruvate to acetyl CoA is irreversible and Acetyl CoA cant be made in glucogenic precursors.
Which parts of the body can exclusively use glucose?
Kidney, Skin and RBC
Which parts of the body can switch to FA as an alternate fuel during starvation?
Other tissues (not brain) ie muscle.
What is the general strategy in the early stages of starvation?
Glucose conservation
Glucose recycling - don’t fully oxidise it - regenerate from lactate
De novo glucose formation (make it from other things).
What happens during the first few hours of starvation?
All the tissues are using glucose. Blood glucose concentration falls
How is hypoglycemia prevented in early starvation?
The liver releases glucose into the bloodstream.
What is glycogenolysis?
Catalyses an equilibrium across the liver cell membrane so glucose concentration in liver cells and blood the same (Through GLUT 2 transporters)
What does an equilibrium across the liver cell membrane and blood signal to the liver cells?
Glucose release comes from glycogen stored in the liver (glycogenolysis - breakdown of the molecule glycogen to glucose)
What is the enzyme that breaks down glycogen in glycogenolysis? How does this occur?
Phosphorylase (rate-limiting step). Phsosphoylase cleaves terminal glycogen molecules to make glucose-1-phosphate which phosphorylates to G-6 - phosphatase.
What happens in glycogenolysis after G-6-Phosphatase is formed?
It is trapped in the cell (too big to leave) so it is transformed into glucose so it can be released by the GLUT-2 transporter into the bloodstream.
Which part of the glycogen molecule is attacked by the enzyme in glycogenolysis?
The end terminal units - the glyosidic link.
How is phosphorylase regulated?
By reversible phosphorylation - only active when phosphorylated by phosphorylase kinase.
What is the chain of events for the regulation of enzymes after phosphorylase?
Card 13
Why is the process of glycogenolysis so complex?
Amplifies signal
More control
What are branch points?
Points in a metabolic pathway in which a compound can be used as a substrate in two or more reactions. The cell must decide which of the pathways to direct the molecule to.
What does a debranching enzyme do to glucose at the branching point? Why?
Releases 10% of the glucose residues as neat glucose instead of G-6-Phosphate. Branching occurs every 10 residues.
Does muscle contribute to euglycemia?
Muscle does not break down glycogen much in starvation because it has no glucagon receptors and no glucose-6-phosphatase (cant release glucose into the blood).
Some glucose residues are able to be released from muscle ______ as _______. Why might this not get to the blood?
Glycogen released as neat glucose - due to the debranching enzyme. The muscle might just use this for itself.
How can muscle contribute to blood glucose levels?
If PDH is inhibited the G^P will go to lactate - to the liver.
How much glycogen is stored in the liver? What does that mean for glycogen depletion?
110g. This is inadequate and the brain will use this in 24 hrs. Need to persuade other tissues to use fat rather than glucose well before liver glycogen is depleted.
What is the purpose of white adipose tissue lipolysis?
Accessing the large reserved of fat in WAT.
What are the steps of WAT lipolysis?
Card 14
What is the key enzyme in WAT lipolysis?
Hydrolyses triglyceride and releases fatty acids - Hormone sensitive lipase.
Where is hormone-sensitive lipase released into?
Into boundary between lipid droplet and cytoplasm and chews away at fat.
High levels of ______ stimulate PDH kinase which converts _____ into inactive phosphorylated form.
Hormone sensitive lipase activates _____ which was deactivated by ______.
Acetyl CoA…..PDH kinase. PDH…..phosphorylation.
In starvation we want PDH to be _____. Why?
Off. Prevents wasteful oxidation of pyruvate. Pyruvate can be made into lactate.
How is glucose oxidation stopped during starvation?
Oxidation of FA switched PDH off by producing a lot of acetyl CoA ( PDH kinase phosphorylates and so it’s inactive). Glucose oxidation cant go ahead without PDH.
Why can’t glucose oxidation occur without PDH?
Pyruvate cant be oxidised to acetyl CoA
When PDH is off what happens to lactate from pyruvate in the muscle?
It is taken in by the liver and remade into glucose by gluconeogenesis. (Cori-cycle)
How much glucose per day can be made from glycerol?
30g