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Regulation of Carbohydrate Metabolism I
Medical School Biochem
21
Biochemistry
Graduate
10/06/2011

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Term
Glycolysis is regulated on what three levels?
Definition
Hexokinase, Glucokinase
Phosphofructokinase-1 (PFK1)
Pyruvate Kinase
Term
Gluconeogenesis is regulated on what three levels?
Definition
Substrate availability (amino acid [alanine] and lactate)

Pyruvate Carboxylase

Fructose 1,6 Bisphosphatase
Term
Why is the first step of glycolysis phosphorylation of the glucose molecule?
Definition
Phosphorylated glucose cannot leave the cell, is essentially trapped
Term
What are the general pathways of metabolic regulation?
Definition
Between cells
Within cells
via Secondary messengers
Term
Intracellular regulation is done in what ways?
Definition
product or substrate concentrations driving reactions or allosteric regulation of enzymes
Term
What are the three general ways that intercellular communication occur?
Definition
Synaptic signalling via neurotransmitters

Endocrine signalling from hormone producing cells

Direct contact between cells (space between cells called gap junction)
Term
What is a secondary messenger?
Definition
molecules in cell that respond after messsenger (hormone etc) binds, helping to cause the ultimate cellular effect
Term
What are the two most widely recognized secondary messengar systems?
Definition
adenyly cyclase system

calcium/phosphatidylinositol system
Term
What are the only cells of the body that do not have carbohydrates as a primary fuel source?
Definition
cardiac cells
Term
Hexokinase IV is predominantly found in which cells?
Definition
Liver and Beta cells of the pancreas
Term
How is Glucokinase regulated in the liver?
Definition
Sequestered and inactivated in the nucleus via Glucokinase regulatory protein (GKRP).

When glucose levels rise at to or above 10mM Glucokinase is released into the cytosol

Increased concentrations of fructose 6-phosphate will increase action of GKRP
Term
How is Hexokinase I-III regulated?
Definition
High concentrations of the product it produces (Glucose 6-phosphate) will inhibit action of Hexokinase
Term
What allosterically inhibits Phosphofructokinase-1?
Definition
ATP and Citrate (citrate is a product of the Krebs cycle)
Term
What allosterically promotes Phosphofructokinase-1 (PFK1)?
Definition
ADP, AMP, and Fructose 2,6-bisphosphate
Term
How is fructose 2,6 bisphosphate created in the liver?
Definition
Activation of Phosphofructokinase-2 in the liver.

This enzyme is active when Glucagon levels are low. Glucagon activates the Adenylyl cyclase cycle which activates the secondary messenger cAMP which activates protein kinase A (PKA) which phosphorylates (read: deactivates) Phosphofructokinase-2 (PFK-2)
Term
What enzyme intermediate upregulates the function of Pyruvate Kinase?
Definition
Fructose 1,6-bisphosphate
Term
How is pyruvate kinase inhibited?
Definition
Phosphorylation via PKA.

Remember PKA is activated through high levels of the hormone Glucagon. Which creates the cascade of adylyl cyclase -> cAMP -> PKA
Term
What is the Cori Cycle?
Definition
The cycle by which the product of anaerobic glycolysis (lactate) is recycled in the liver (gluconeogenesis) and then returned as glucose to the anaerobic tissue
Term
What is the effect on Gluconeogenesis by Acetyl Coa?
Definition
High levels with deactivate pyruvate dehydrogenase and activate Pyruvate Carboxylase
Term
How is Fructose Biphosphatase 1 (FBPase-1) inhibited?
Definition
By AMP and Fructose 2,6 Bisphosphate
Term
How do hormones regulate genetic expression of key enzymes in Glycolysis?
Definition
Increase in insulin or glucagon for a prolonged period of time regulates the transcription of Glucokinase, PFK-1, and Pyruvate Kinase
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