Lecture 31: Urea Cycle, Metabolic Priorities, and Diabetes Flashcards Preview

SMP - MNE Exam 2 > Lecture 31: Urea Cycle, Metabolic Priorities, and Diabetes > Flashcards

Flashcards in Lecture 31: Urea Cycle, Metabolic Priorities, and Diabetes Deck (81)
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Urea Cycle Step 5: Reactants/Products?

Arginine + H2O => ornithine + urea


What happens to the ornithine regenerated in the 5th step of the UC?

Goes back in the mito for another round


How does the urea cycle reinforce the second metabolic priority?

When levels or arginine and ornithine are low it means that gluconeogenesis is high (arginine is glucogenic and ornithine is made from glutamate which is glucogenic), so you want the urea cycle to be slowed down to prevent protein catabolism


What does the rate of the urea cycle depend on?

Levels of:
1. Ornithine
2. Aspartate



Is the urea cycle energetically expensive?

No because it generates NADH:
1. The first NH4+ added comes from this reaction: Glutamate + H2O + NADP/NAD+ => alpha-ketoglutarate + NADPH/NADH + NH4+
2. Fumarate enters TCA after being formed in step 4 of UC and is converted to malate, forming NADH

TOTAL: 2 NADH formed = 5 ATP

Energy used: 4 high energy bonds = 2 ATP broken down into 2 ADP + 1 ATP broken down into AMP (2)


Where does the aspartate used in step 3 of the urea cycle come from?

Oxaloacetate + glutamate = aspartate + alpha-ketoglutarate


What are the 2 fates of the fumarate formed in step 4 of the urea cycle?

1. Well-fed: enters mitosol to enter TCA to be converted to malate and continues through the TCA
2. Starvation: stays in cytosol and is converted to malate => to oxaloacetate => to phosphoenolpyruvate through gluconeogenesis


Describe the starvation metabolism. What hormones cause this?

High catecholamines AND low insulin =>
1. TAG breakdown to liberate FFAs
2. Ketogenesis because TCA intermediates are being used for gluconeogenesis so not enough of them for acetyl-CoA to enter the TCA
3. Low glucose uptake by muscle and adipocytes
4. Proteolysis to generate TCA cycle intermediates to be used in gluconeogenesis


How is the pH drop from ketogenesis balanced out? 3 mechanisms

1. Kidney released NH4+ since it can perform gluconeo but not urea cycle
2. Other organs release K+
3. Kussmaul breathing


What is the most dangerous effect of ketoacidosis?

Neurons release their K+ to counter balance the pH drop which messes up their RMP


What is nonketotic hyperosmolar coma? To what patients does this happen?

Hyperglycemia => water sucked out of cells => excretion of many critical solutes => coma



What is the lipostat theory? Describe the mechanism.

Adipose tissue is an endocrine organ secreting leptin which feeds back on the hypo to inhibit appetite, stimulate FA beta oxidation, and increase insulin sensitivity
1. Leptin secreted binds to hypo
2. Hypo stimulates sympathetic nervous outflow to release norepi on adipocytes
3. Norepi binds to beta-adrenergic receptors: Gs cascade activating PKA:

- PKA phosphorylates hormone sensitive lipase and perilipin = phosphorylates perilipin = TAGs available for HSL to break them down
- PKA upregulates the expression of uncoupling proteins so fatty acid beta oxidation is increased cause energy is being waster through thermogenesis


What 2 experiments confirm the lipostat theory?

1. (ob/ob) knockout mice (double knockout of the leptin gene) become obese and insulin resistant
2. (db/db) knockout mice (double knockout for the leptin receptor gene) become obese and insulin resistant


Why are leptin knockout mice unable to stay warm?

They are unable to do this:
1. Leptin secreted binds to hypo
2. Hypo stimulates sympathetic nervous outflow to release norepi on adipocytes
3. Norepi binds to beta-adrenergic receptors: Gs cascade activating PKA
4. PKA upregulates expression of uncoupling proteins for brown fat to create heat


How does leptin increase the sensitivity to insulin?

1. Leptin's receptor is also a protein kinase and helps insulin phosphorylate IRS-2 which then activates PI-3K
2. Leptin activates AMP-dependent protein kinase (AMPK) which phosphorylates similar substrates as the insulin receptor (eg: PKB)


How is leptin secreted in obese peeps?

The hormonal activity of the adipose tissue is dysfunctional and leptin is not secreted as well


What is the role of adiponectin? What is it secreted by? For who is this hormone important?

Produced and released by adipose tissue and also activates AMPK


What effects does AMPK have on the muscles and liver? What is its overall goal?

1. Helps muscle take up glucose and FAs
2. Promotes FA beta oxidation especially during exercise

3. Inhibits FA synthesis in the liver



Other than leptin and adiponectin, what else stimulates AMPK in cells? How does this work?

EXERCISE! ATP is used up = AMP is produced = AMPK is activated


Why is it important to preserve proteins during starvation?

You want to avoid wasting away enzymes needed for catalysis


What is the predominant source for gluconeogenesis during starvation?

Glycerol for TAGs


Difference between CPS-I and II?

CPS-I: uses glutamate in the mitosol

CPS-II: uses glutamine in the cytosol


Where do the 2 nitrogens in the urea cycle come from?

1. Glutamate
2. Aspartate


Describe the mechanism in Step 3 of the Urea Cycle.

AMP is attached to citrulline, and then Nu substitution of AMP and aspartate


What exactly happens in Step 4 of the Urea Cycle?

The carbon skeleton of aspartate is reduced and released = fumarate


What is citrulline?

A 6C nonstandard AA: not used in protein synthesis, intermediate of UC


What does dearth mean?

Lack of something/low levels of something


What do low amounts of TCA intermediates mean?

Low levels of glucogenic AAs, meaning they are being used for gluconeogenesis


What is the main hormone of starvation?



What happens to the excess nitrogen in the kidney during starvation, since this organ can perform gluconeogenesis but not the urea cycle?

Secreted to balance out the drop in pH due to ketogenesis