Gluconeogenesis

Question 1

Def

Answer 1

Formation of glucose from non carbohydrate precursors like
• pyruvate
• lactate
• glycerol
• glucogenic a.a
• propionyl CoA
During starvation and late fasting

Question 2

Location

Answer 2

Organ location: in liver and less in kidney

Cellular location: partly mitochondrial and partly cytosol

Question 3

Steps

Answer 3

It is as reversal of the glycolysis but there is some energy barriers that prevents this reverse but can be treated and they are :-
• pyruvate kinase ** pyruvate carboxylase
PEP carboxykinase

• PFK -1 **** fructose 1,6 biphosphatase

• glucokinase ** glucose 6 phosphatase in liver and kidney and absent in muscle

Question 4

Carboxylation of pyruvate

Answer 4

Pyruvate is converted to OAA by pyruvate carboxylase ( biotin and ATP ) in mitochondria

And then converted to PEP by PEP caroxykinase in cytosol
But OAA is unable to be transported to cytosol so it is converted to malate by mitochondrial MD ( NADH ~> NAD ) as malate can cross to cytosol and then it is re oxidized to OAA by cytosolic MD ( NAD ~> NADH)

Question 5

The overall equation of gluconeogensis

Answer 5

2 pyruvate + 6 ATP + 2NADH ~> glucose + 6 ADP + 2NAD

Question 6

Energy cost

Answer 6

*( NADH /NAD) ~> oxaloacetate to malate
* ( NAD/ NADH) ~> malate to OAA راحوا مع بعض
* ( NADH / NAD) ~> 1,3 biphosphoglycerate to glyceraldehyde 3 p
=1 NADH / NAD

• ATP / ADP ~> pyruvate carboxylase
• ATP / ADP ~> PEP carboxykinase
• ATP / ADP ~> phosphoglycerate kinase
  = 3 ATP /ADP

To form glucose we need 2 pyruvate
So it is 2 NADH AND 6 ATP CONSUMED
So it

Question 7

Substrates for gluconeogensis

Answer 7

1- lactate
By lactate dehydrogenase, lactate is formed in sk ms and RBC is transported to liver and converted to pyruvate through cori cycle

2- glucogenic a.a
•They are ( alanine - aspartic acid - glutamic acid etc)
•In starvation and DM , they are transaminated to the corresponding carbon skeletons and then enter TCA to give OAA and then glucose

•Alanine in muscle is a major substrate
•Alanine is transported to liver and transaminated to pyruvate and then pyruvate convert to glucose, glucose can enter glycolysis and produce pyruvate that is transaminated to alanine and so on ( alanine cycle

Glycerol : results from lipolysis of TAG in adipose tissue , glycerol kinase in liver and other tissues except adipose tissue and muscles convert it to glycerol 3 phosphate that can convert to DAHP by glycerol 3 phosphate dehydrogenase

Propionyl CoA : results from oxidation of odd f.a chain and carbon skeletalon of some a.a ( isoleucine- valine - methionine) and then converted to succinyl CoA but is a minor source for glucose ( قولي ازاي )

Question 8

Regulation of gluconeogensis

Answer 8

Key enzymes: pyruvate carboxylase and PEP carboxykinase and fructose 1,6 biphosphatase and glucose 6 phosphatase

When Glycolysis is active , gluconeogensis is inactive

Gene expression ( long term)

1- hyperglycemic hormones : g hormones stimulates all key enzymes
2- insulin inhibits them

Short term ( Allosteric effect)
Pyruvate carboxylase : activated by acetyl CoA

Fructose 1,6 biphosphatase : activated by ATP and citrate and inhibited by AMP and fructose 2,6 biphosphate

Question 9

Importance of gluconeogensis

Answer 9

1-The process of gluconeogenesis is important for
Glucose supply when carbohydrates
are not available in the diet.

2. Continuous supply of glucose is especially im-
   portant for:
   a. Nervous system
   b. Erythrocytes
   c.Skeletal muscle especially under anaerobic conditions
   d. Formation of lactose, the milk sugar, in mammary glands
   e.Glucose is the only fuel for fetus.
   3-Glucose is also important for maintaining ctric acid cycle, as it is the main source of pyruvate
   4-Gluconeogenic process is used to clear the body from lactate that is formed in sk ms during exercise and Rbcs ( cori cycle)