8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
1/23
1
23.7 Glycogen Metabolism
23.8 Gluconeogenesis: Glucose Synthesis
Chapter 23 Metabolic Pathways
for Carbohydrates
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
2/23
2
Glycogenesis
Glycogenesis:
Stores glucose by converting glucose to
glycogen. Operates when high levels of glucose-6-
phosphate are formed in the first reaction of
glycolysis.
Does not operate when energy stores(glycogen) are full, which means that
additional glucose is converted to body fat.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
3/23
3
Diagram of Glycogenesis
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
4/23
4
Formation of Glucose-6-Phosphate
Glucose is converted to glucose-6-phosphate
using ATP.
Glucose-6-phosphate
HH
H
H
H2P
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
5/23
5
Formation of Glucose-1-Phosphate
Glucose-6-phosphate is converted
to glucose-1-phosphate.
Glucose-6-phosphate Glucose-1-phosphate
O
O
OH
OH
OH
H2OH
O
OH
OH
OH
OH
H2OP
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
6/23
6
UDP-Glucose
UTP activates glucose-1-phosphateto form UDP-glucose and
pyrophosphate (PPi).
UDP-glucose
O
O
OH
OH
OH
H2OH
PO
O-
O PO
O-
O CH2O
OHOH
N
N
O
H
O
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
7/23
7
Glycogenesis: Glycogen
The glucose in UDP-glucose adds to glycogen.
UDP-Glucose + glycogen glycogen-glucose + UDP
The UDP reacts with ATP to regenerate UTP.
UDP + ATP UTP + ADP
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
8/23
8
Glycogenolysis
Glycogenolysis
is the break
down ofglycogen to
glucose.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
9/23
9
Glycogenolysis
Glycogenolysis:
Is activated by glucagon (low blood glucose).
Bonds glucose to phosphate to form glucose-1-phosphate.Glycogen-glucose + Pi Glycogen + glucose-1-phosphate
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
10/23
10
Isomerization of Glucose-1-
phosphate
The glucose-1-phosphate isomerizes to glucose-
6-phosphate, which enters glycolysis for energy
production.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
11/23
11
Glucose-6-phosphate
Glucose-6-phosphate:
Is not utilized by brain and skeletal muscle
because they lackglucose-6-phosphatase. Hydrolyzes to glucose in the liver and kidney,
whereglucose-6-phosphatase is available providing
free glucose for the brain and skeletal muscle.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
12/23
12
Utilization of Glucose
Glucose:
Is the primary
energy source for thebrain, skeletal
muscle, and red
blood cells.
Deficiency canimpair the brain and
nervous system.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
13/23
13
Gluconeogenesis: Glucose
Synthesis
Gluconeogenesis is:
The synthesis of
glucose fromcarbon atoms of
noncarbohydrate
compounds.
Required whenglycogen stores are
depleted.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
14/23
14
Gluconeogenesis: Glucose
Synthesis
Carbon atoms for gluconeogenesis from lactate,
some amino acids, and glycerol are converted to
pyruvate or other intermediates. Seven reactions are the reverse of glycolysis and
use the same enzymes.
Three reactions are not reversible.
Reaction 1 HexokinaseReaction 3 Phosphofructokinase
Reaction 10 Pyruvate kinase
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
15/23
15
Gluconeogenesis: Pyruvate to
Phosphoenolpyruvate
Pyruvate adds a carbon to form oxaloacetate by
two reactions that replace the reverse of reaction
10 of glycolysis. Then a carbon is removed and a phosphate added
to form phosphoenolpyruvate.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
16/23
16
Phosphoenolpyruvate to Fructose-
1,6-bisphosphate
Phosphoenolpyruvate is converted to fructose-
1,6-bisphosphate using the same enzymes in
glycolysis.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
17/23
17
Glucose Formation A loss of a phosphate from fructose-1,6-
bisphosphate forms fructose-6-phosphate and Pi.
A reversible reaction converts fructose-6-phosphate to glucose-6-phosphate.
The removal of phosphate from glucose-6-
phosphate forms glucose.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
18/23
18
Cori Cycle
When anaerobic conditions occur in active
muscle, glycolysis produces lactate.
The lactate moves through the blood stream to theliver, where it is oxidized back to pyruvate.
Gluconeogenesis converts pyruvate to glucose,
which is carried back to the muscles.
The Cori cycle is the flow of lactate and glucosebetween the muscles and the liver.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
19/23
19
Pathways for Glucose
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
20/23
20
Regulation of Glycolysis and
Gluconeogenesis
High glucose levels and insulin promote glycolysis.
Low glucose levels and glucagon promote
gluconeogenesis.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
21/23
21
Ethanol Ethanol is not a carbohydrate, nor is it a precursor for the biosynthesis
of carbohydrates.
However, ethanol can replace sizable amounts of carbohydrates as anenergy source when large amounts are ingested.
It is present in the blood of most humans, being produced by intestinalflora.
People ingest ethanol in variable amounts in beverages and fermentedfruits.
Ethanol is metabolized in the liver to acetate and adds to the caloriccontent of the diet.
Ethanol has an energy equivalent of 7 kcal/g.
100 mL of table wine has ethanol corresponding to about 72 kcal.
A jigger of whiskey furnishes approximately 120 kcal.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
22/23
22
Ethanol continue: When ethanol is metabolized in the liver, alcohol dehydrogenase oxidizes it first to
acetaldehyde.
CH3CH2OH + NAD+ CH3CHO + NADH + H
+
The acetaldehyde is oxidized further to acetate.
CH3CHO + NAD+
+ H2O CH3COO-
+ NADH + H+
A small fraction of the alcohol may be oxidized by other systems: Cytochrome P450 oxidase (also involved in detoxification of many drugs);
Catalase
The acetate produced from ethanol largely escapes from the liver and is converted toacetyl CoA and then to carbon dioxide by the way of the Krebs cycle.
The acetyl that stays in the liver may act as a precursor for lipid biosynthesis.
A significant consequence of metabolism of ethanol in the liver is the twofold tothreefold increase in the NADH/NAD+ ratio.
With higher concentrations of blood alcohol, the concentration of NADH remains high,and the availability of NAD+ drops and limits both the further oxidation of ethanol andthe normal functioning of other metabolic pathways, such as gluconeogenesis.
8/6/2019 Ch.23.3glycogen Metabolism Gluconeogenesis
23/23
23
Fatty liver Chronic consumption of significant amounts of
alcohol may lead to a fatty liver, in which theexcess of triacylglyceride is deposited.
This is caused by several contributing factors: Reduced triacylglyceride secretion from the liver
Reduced rates of fatty acid oxidation
Increased rates of lipid biosynthesis
These processes are associated with the increasedacetyl CoA and NADH/NAD+ ratio in the liverthat results from ethanol oxidation.