Biochemistry-Fed and Fasting Metabolism Flashcards
What are healthy blood glucose levels?
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What is renal threshold?
Your blood glucose levels are so high that it gets into the urine.
Why do you get shaky and irritated when you are hypoglycemic?
Fatty acids cannot cross the blood-brain barrier. This makes glucose the main source of metabolism for the brain. When you are starving the brain uses ketone bodies as fuel to reduce glucose demand by about 75%.
If you eat at 0 hours, how does the blood glucose source change over time?
Hours 1-4 = Food from gut. Hours 3-24 = Glycogen from liver. Hours 8-40 days = Gluconeogenesis in liver. Fatty acids begin to mobilize at about 6 hours, where a portion will go to the liver and become ketone bodies where they will be used at days 3-4.
Why do your muscles feel weaker when you wake up in the morning?
The body cannot convert fatty acids to glucose for brain fuel while sleeping, so the body must use gluconeogenesis at about hour 6 of fasting, which breaks muscle protein down to Ala which is converted to pyruvate and then to glucose.
During the basal state, blood glucose and insulin are down and glucagon levels are up. How does this hormone affect metabolism?
It binds to liver receptors and causes glycogen to break down and release free glucose into the blood (especially for brain and RBCs). It also binds adipose tissue and causes triglyceride release into the blood (preferred by muscle and liver). Excess Acetyl-CoA in liver after TCA cycle forms ketone bodies and those are released into the blood (used by muscle/heart/brain). Muscle protein is also broken down in gluconeogenesis to form glucose with urea byproduct.
What are ketone bodies?
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When are fatty acids and ketone bodies mobilized?
Increased epinephrine, glucagon and decreased insulin. (Fasting, starvation, high fat/low carb diet and aerobic exercise)
What tissues do and don’t use ketone bodies?
As you get deeper into starvation, adipose, muscle, heart and intestinal tissue switch to fatty acid use and leave the ketone bodies for the brain.
How long does it usually take before the body begins to adapt to starvation?
3-4 days. This is when ketone bodies are routed to the brain exclusively.
Why is it said that ketone bodies have a protein sparing effect on the body?
Ketone bodies come from fatty acids, which are packed with a greater amount of energy than glucose. If the brain can essentially use fatty acids to produce ketone bodies instead of raw glucose, you don’t need to do as much gluconeogenesis, which gets its intermediates from break down of muscle.
Why do people on the Atkins diet smell funny?
In ketone body synthesis, 2 acetyl-CoA condense to eventually become acetoacetate and D-beta-hydroxybutyrate. The acetoacetate can decarboxylate to acetone which smells funny.
Why do people with type I diabetes go into diabetic coma?
Insulin plays a role in suppressing fatty acid mobilization. When people are deficient in insulin they mobilize lots of fatty acids and the liver converts those to ketones. Mass amounts of ketone in the blood results in acidosis and diabetic coma.
How are ketone bodies oxidized for energy in peripheral tissues?
D-beta-hydroxybutyrate is oxidized to acetoacetate. Acetoacetate interacts with succinyl Co-A to form succinate and acetoacetyl-CoA. Acetoacetyl-CoA reacts with another CoA to form 2 Acetyl CoA molecules.
Why can’t the liver use the ketone bodies for energy that it produces?
It lacks the enzyme that transfers succinyl-CoA’s CoA to acetoacetate (acetoacetate CoA transferase)
Where does the liver get its energy from? Why does it produce a lot of ketone bodies as opposed to TCA cycle oxidation of acetyl-CoA?
Beta-oxidation of fatty acid creates lots of NADH that is sent to hepatic mitochondria. High levels of NADH suppressed oxidation in the TCA cycle. This routes Acetyl-CoA to ketone body synthesis.
What linkages make up glycogen?
alpha-1,4 and alpha-1,6 linkages
How do you get so much glucose release from glycogen phosphorylase activity? How is glucose released?
It acts at the nonreducing ends of all the glycogen chains via phosphorylitic cleavage. Inorganic phosphate attacks C1 and splits the glycosidic linkage, releasing glucose-1-phosphate.
Why do you get more energy from glycogen in muscle vs. glycogen in the liver?
Glycogen in muscle can start glycolysis with gluc-6-P and skip the step where you use 1 ATP, getting a net 3 ATP from glycolysis. The liver must convert glycogen to glucose before it can go into the blood stream. This requires the tissue to use an ATP to make gluc-6-P when starting glycolysis.
At what point in glycogenolysis do you need debranching enzyme to come to the rescue?
When there are 4 glucose residues before the branch point.
How is UDP-glucose synthesized?
Glucose-1-P attacks the alpha-P group of UTP. Pyrophosphate is released and UDP-Glucose is formed.
Where does addition of new glucose residue occur in glycogen? What drives synthesis forward?
At a primer on the nonreducing end of a glycogen chain. Bond formation at the C4 carbon of UDP-glucose kicks off UDP and adds glucose to the glycogen chain.
How are the different branches formed during glycogen synthesis?
Transferases move chains to the interior once they get so long.
What would happen if glycogen and glucose-6-P synthesis could occur at the same time?
You get a futile cycle. Nothing is generated and ATP is expended.
How does the body avoid futile cycling in glycogen metabolism?
Reciprocal regulation of glycogen phosphorylase (glycogenolysis) and glycogen synthase (glycogen synthesis).
What reactions do you expect to see going on as far as regulation goes in the fast vs. fed state?
Fasting state = protein kinase reactions induced by glucagon/epinephrine. Fed state = phosphatase reactions induced by insulin.
How does phosphorylation of glycogen phosphorylase and glycogen synthase affect their activity?
When glycogen phosphorylase is phosphorylated it becomes activated. When glycogen synthase is phosphorylated, it becomes inactivated.
