MMP Gluconeogenesis and Blood Glucose Levels

Primary site of gluconeogenesis

liver

gluconeogenesis

generation of glucose from non-carbohydrate source

Blood glucose, insulin, and glycogen levels after a meal

Glucose = increase

Insulin = Increase

Glycogen = Decrease

Where does gluconeogenesis occur during extreme fasting

kidney cortex

What stimulates gluconeogenesis?

decrease in insulin, increase in glucagon

Purpose of gluconeogenesis

Maintain normal, physiologic blood glucose levels during prolonged periods of fasting

Increased ketone bodies provide fuel without breaking down excess ______.

protein

when does the rate of gluconeogenesis decrease

during long term starvation to preserve protein

3 Precursors of gluconeogenesis

1. Lactate

2. Glycerol

3. Amino Acids - Alanine

Conversion of lactate to pyruvate:

enzyme?

What does it generate?

lactate dehydrogenase

generates NADH

Conversion of Alanine to pyruvate:

enzyme?

What does it generate?

alanine aminotransferase

generates glutamate

Conversion of Glycerol to Dihydroxyacetone Phosphate:

enzymes?

Does it use energy

What does it generate?

glycerol kinase and glycerol 3-P dehydrogenase

- 1st step = uses ATP

- generates NADH

What is Phosphoenolpyruvate required for?

AA and lactate activation of gluconeogenesis

What activate gluconeogenesis

Stems from oxaloacetate being converted to PEP

Where does conversion of PEP to pyruvate occur

the liver

Conversion of Pyruvate to PEP:

pyruvate converted to __________

OAA "shuttled" out of _______

OAA converted to ______

Conversion of Pyruvate to PEP:

pyruvate converted to OAA

OAA "shuttled" out of mitochondria

OAA converted to PEP

Where does the conversion of OAA to PEP occur

the cytosol

Transamination of ______ to form oxaloactetate.

aspartate

What does the conversion of OAA to PEP subsequently produce?

Glucose

Where do most of the steps for the conversion of PEP to glucose occur?

the cytosol

PEP to Fructose 1, 6 bisphosphate:

For every ____ molecules of Glyceraldehyde 3-Phosphate generated ___ is converted to DHAP.

For every 2 molecules of Glyceraldehyde 3-Phosphate generated 1 is converted to DHAP.

Enzyme for the conversion of F 1,6 -BP to F6P

Fructose 1,6-bisphosphatase

Enzyme for the conversion of F6P to G6P

Phosphoglucose isomerase

Enzyme for the conversion of G6P to Glucose

Glucose 6-Phosphatase

- hydrolyzes pi from G6P

Where is Glucose 6-Phosphatase located?

ER membrane

What stimulates gluconeogenesis?

Prolonged exercise

High protein diet

Stress

Primary substrates for gluconeogenesis

Glycerol

Lactate

Amino Acids

Regulation sites of gluconeogenesis

1. Pyruvate to PEP

2. F 1,6 BP to F6P

3. G6P to glucose

What initially decrease during fasting

ADP

What does a decrease in ADP cause?

- phosphorylation of pyruvate dehydrogenase, inactivating the enzyme

- increase of conversion to pyruvate to OAA in the mitochondria

What activates pyruvate carboxylase

Acetyl CoA

What does increase in Acetyl CoA

decrease in utilization of pathway

example of negative feedback

regulation of pyruvate to PEP

What alters PEPCK expression levels?

hormonal changes

Glucagon = _____ in cAMP = ______ in CREB

Increase, Increase

CREB

transcription factor that increases the expression of PEPCK

Pyruvate kinase inactivation works to ______ PEP formation

increase

decreased conversion to pyruvate, ______ PEP concentration

increase

increase in glucagon = _____ pyruvate kinase activity

decrease

Final step of gluconeogenesis prior to glucose being released from hepatocytes

G6P to Glucose

What is essentially inactive during gluconeogenesis?

Glucokinase

Drop in blood glucose indicates need for _________

gluconeogenesis

Glucokinase has a _____ Km for glucose

high

The three precursors are converted to what 2 required molecules that initiate glycolysis?

Pyruvate and dihydroxyacetone phosphate

Enzyme involved in gluconeogenesis that is an example of negative feedback?

Pyruvate carboxylase