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Gluconeogenesis
Opt 500, Lecture on 9/30/11
38
Biochemistry
Professional
10/20/2011

Additional Biochemistry Flashcards

 


 

Cards

Term
How long can liver glycogen meet the needs of glucose to the body?
Definition
10-18 hours
Term
Precursors for glucose during a prolonged fast
Definition

Lactate, pyruvate, glycerol

alpha ketoacids

Term
What substrates directly enter gluconeogenesis?
Definition
pyruvate and oxaloacetate
Term
name two ketogenic amino acids
Definition

Leucine and Lysine

 

These break into acetoacetate

Term
Can glucose be formed by reverse glycolysis?
Definition
No, because the equilibrium of glycolysis STRONGLY favors the formation of pyruvate.
Term

Organ that plays main role in overnight fasting?

In emergencies?

Definition

Liver for overnight, 90% contribution while kidney only contributes 10%

 

In emergencies- kidneys will help 40%

 

 

Term

Hydrolysis of TGs:

yields what?

where does it happen?

where does the product go?

Definition

Yields glycerol!

Happens in adipose tissue

Delivered to liver by blood

Term
Cori Cycle
Definition

Blood bourne glucose is converted into lactate in sk muscle

 

muscle then releases lactate into the blood

 

lactate diffuses into liver and is reconverted into glucose

Term
Major glucose source for fasting
Definition
Amino acids from hydrolysis of tissue proteins (proteins are usually a last source for this process)
Term
Indirect substrates for gluconeogenesis
Definition
lactate, glycerol, glucogenics amino acids
Term
In gluconeogenesis, Pyruvate needs to be converted to what?
Definition
Phosphoenopyruvate
Term
Describe the first 4 reactions of gluconeogenesis
Definition

First 2 rxns in mitochondria, then converts to malate to travel via the malate shuffle. travels into cytoplasm for remaining reactions .

 

Term
Conversion of pyruvate
Definition
pyruvate is carboxylated by pyruvate carboxylase to OAA, then converted to PEP by the action of PEP-carboxykinase
Term
What purposes does OAA serve in the mitochondria of liver and kidneys?
Definition

provides substrate for gluconeogenesis

 

OAA can replenish TCA cycle (muscles use OAA for this purpose)

Term
How is pyruvate carboxylase activated?
Definition
It is allosterically activated by binding of acetyl CoA
Term
What happens to malate once it is transported from mitochondria to cytosol?
Definition
Malate must be reoxidized to OAA by cytosolic malate dehydrogenase
Term
Role of NADH in transfer of OAA across mitochondria
Definition
NADH is oxidized to NAD+ to convert OAA to malate so it can cross mitochondria via malate shuttle to cytosol
Term
What happens to malate once it is in the cytosol?
Definition

Malate will be reozidized into OAA.

 

OAA is converted to phosphoenolpyruvate by PEP carboxykinase

Term

PEP will be acted on by reverse glycolysis until what step?

 

What happens when this step is reached?

Definition

Until F 1,6 BP

 

Which will be hydrolzyed by F 1,6 BPase. Irreversible dephosphorylation by BFPK-1 will form F6P

Term
Can muscle glycogen maintain blood glucose levels
Definition
No- muscle lacks G6P, which is the final enzyme that is converted into glucose. Therefore, muscle recieves energy frm glycolysis and NOT from gluconeogenesis
Term
3 irreversible steps of glycolysis
Definition

1. glucose is converted to G6P by hexokinase

 

2. Fructose-6-phosphate is converted to Fructose 1,6 BP by PFK-1

 

3. Phosphoenolpyruvate converts to pyruvate by pyruvate kinase

Term
Gluconeogenesis leads to the formation of what 3 things?
Definition

GLUCOSE!

PEP

F6P

 

Comes at the cost of 6 ATP and 2 NADH for every glucose

Term
Direct activators of gluconeogenesis
Definition

AcCoA

 

ATP

Term
Indirect activators of gluconeogenesis
Definition
Glucagon and epinephrine
Term
Steps of gluconeogenesis (irreversible)
Definition

1. using PEP carboxylase to convert oxaloacetate to PEP

 

2. Using F6BPase to form Fructose-6-P from F1,6-BP

 

3. Using G6Pase to form glucose from G6P

Term
3 mechanisms by which glucagon stimulates gluconeogenesis
Definition

1. Lowers F2,6BP, activates F1,6Pase, inhibits PFK

 

2. increases cAMP, activates PKA, phosphorylates pyruvate kinase, degrades PEP to pyruvate

 

3. increases transcription of PEP carboxykinase

Term
Function of AcCoA
Definition

activates pyuvate decarboxylase during fasting.

Excessive lypolysis will increase levels of AcCoA

 

it also inhibits pyruvate dehydrogenase, which diverts pyruvate towards gluconeogenesis

Term
Result of low insulin levels
Definition
AAs are mobilized from skeletal muscle to provide glucogenic carbon skeletons
Term
Why can't glucose be formed by reversal of glycolysis?
Definition

equilibrium favors pyruvate formation, using mit and cystolic enzymes.

 

overnight fast is 90% gluconeogenisis in liver, 10% in kidneys.

prolonged fasting is 40% kidneys (only in emergency)

Term
Glycerol
Definition
phosphorylated & become substrate in glycolytic path after TG is broken down
Term

Carboxylation of pyruvate

(first road block of gluconeogenesis)

Definition

pyruvate carboxylated by pyruv carboxylase (activated by acetyl CoA) to OAA > PEP (by PEP carboxykinase)

 

Biotin bound to lysine. ATP hydrolyzes to carboxy pyruvate to ALSO make oaa.

 

OAA (substrate for gluconeogenesis, replenish TCA)

Term

Transport of OAA to cytosol

(part two of gluconeogenesis)

Definition

converts to PEP (which is in both mit & cytosol)

 

Mit PEP goes to cytosol via transporter

Cytosol PEP is the transporter, but OAA reduced to malate first. (by malate dehydrogenase)

 

reoxidized to OAA by cyt malate dehydrogenase once in cytosol.

Term

Decarboxylation of cyt OAA & dephosphorylation of F1,6BP

(step 2/3 gluconeogenesis)  

Definition

OAA > PEP in cytosol (by PEP carboxykinase..needing GTP)

PEP > F1,6 BP via reverse rxn > hydrolyzed by F16BPase > F6P (phosphotase removes phosphate to become F6P)

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