5. Introduction
Storage form of carbohydrates in
animals
Sites: Liver & muscle
Glycogen:
Functions
Liver glycogen is used to maintain blood
glucose.
Muscle glycogen supplies energy during
muscle contraction.
6. Glycogenesis
It is the synthesis of glycogen from glucose.
Tissue : Liver & muscle
Intracellular site : Cytosol
Requirements : Glycogen primer
UTP, ATP
Reactions :
Synthesis of UDP-Glucose.
Adding glucose units to glycogen primer to form
linear chain of glycogen by glycogen synthase
Formation of branches by branching enzyme
to form glycogen.
7. 1. Synthesis of UDP-Glucose.
Glucose
glucokinase (liver)
ATP
hexokinase (muscle)
ADP
Glucose-6- phosphate
phosphoglucomutase
Glucose-1- phosphate
UDP-glucose
pyrophosphorylase
UTP
PPi
UDP -glucose
( UDP - )
11. 3. Elongation of branches to form glycogen.
1-6- bond
Elongation by
glycogen synthase
Formation of branches
by branching enzyme
Glycogen
12.
13. Glucose
ADP
glucokinase (liver)
ATP
hexokinase (muscle)
Glucose-6- phosphate
phosphoglucomutase
Glucose-1- phosphate
UDP-glucose pyrophosphorylase
PPi
UTP
(UDP UDP -glucose
glycogenin
OH
Glycogen initiator synthase
UDP
Glycogen primer
13 UDP
Glycogen synthase
13UDP
Branching enzyme
Elongation by glycogen synthase
Formation of branches by branching
enzyme
Glycogen
14. Glycogenolysis
It is the degradation of glycogen stored in
liver and muscle to glucose.
Glycogenolysis is not the reverse of the
glycogenesis but is a separate pathway .
Tissue : Liver & muscle
Intracellular site : Cytosol
Reactions :
Action of glycogen phosphorylase.
Action of debranching enzyme.
Formation of glucose -6 - phosphate.
15. Action of glycogen phosphorylase.
Glycogen
Pi
Glycogen phosphorylase
nGlucose-1 ph
Limit dextrin
22. Regulation of glycogen metabolism
Glycogenesis and gluconeogenesis are controlled
by the enzymes glycogen synthase and glycogen
phosphorylase.
Regulation of these enzymes is accomplished by 2
mechanisms
1.Covalent modification
-brought about by Hormones
2. Allosteric regulation.
-brought about by substrates
23. Regulation of glycogen metabolism...
glycogen synthase and glycogen
phosphorylase are said to be
RECIPROCALLY REGULATED
That is, when one enzyme is active, the other
one is inactive.
RECIPROCALLY REGULATION is brought about
by hormones, by COVALENT MODIFICATION
OF THE 2 ENZYMES.
24. COVALENT MODIFICATION OF
THE 2 ENZYMES
-Addition or removal of a group (phosphate
group) makes the enzyme either active or
inactive.
glycogen phosphorylase is active in
PHOSPHORYLATED Form. (inactive in
dephoshorylated form)
glycogen synthase is active in
DEPHOSPHORYLATED Form. (inactive in
dephoshorylated form)
26. Regulation of glycogen degradation by c AMP
During fasting condition and muscle contraction……
Glucagon,Epinehrine,Ca++
c AMP
Via protein kinase and
phosphorylase kinase
Glycogen phosphorylase b
(dephosphorylated Inactive)
Glycogen phosphorylase a
(phosphorylated active)
Glycogenolysis
27. Regulation of glycogen formation by c AMP
During fasting condition and muscle contraction……
Glucagon,Epinehrine,Ca++
c AMP
Via protein kinase and
phosphorylase kinase
Glycogen synthase a
(dephosphorylated active)
Glycogen synthase b
(phosphorylated inactive)
Glycogenesis stopped
28. Regulation of glycogen formation by insulin
During fed state and in resting muscle ……
insulin
phosphatase
PO4
Glycogen synthase b
(phosphorylated inactive)
Glycogen synthase a
(dephosphorylated active)
Glycogenesis++
29. Regulation of glycogen degradation by insulin
During fed state and in resting muscle ……
insulin
phosphatase
PO4
Glycogen phosphorylase a
(phosphorylated active)
Glycogen phosphorylase b
(dephosphorylated inactive)
Glycogenolysis stopped
30. Allosteric regulation.
• Glucose 6-po4, and ATP are allostearic
modulators.
• They activate
• Glycogen synthase
• Inhibit glycogen phoshorylase
31. Allosteric regulation
Glucose 6-po4, and ATP are allostearic modulators.
activate Glycogen
synthase
glycogenesis
Inhibit glycogen
phoshorylase
glycogenolysis
This Occurs in fed
state
34. Glycogen storage disorders
These are a group of genetic disease that result from
a defect in an enzyme required for glycogen
synthesis or degradation .
The enzymes defect may be either generalized
(affecting all tissues) or tissue-specific
(liver, muscle, kidney, intestine, myocardium)
They result in either formation of glycogen that has an
abnormal structure or the accumulation of excessive
amounts of normal glycogen in specific tissues.
35. Glycogen storage disorders
Type Name
Deficient enzyme
Features
I
Von
gierke’s
disease
Glucose- 6phosphatase
Hepatomegaly,
fasting hypoglycemia,
lactic acidosis,
hyperuricemia
II
Pompe’s
disease
Lysosomal
maltase
Accumulation of
glycogen in lysosomes
of liver, heart,
muscle. Death before
2yrs
36. III Limit
dextrinosis/
Cori’s disease
Debranching
enzyme
IV Amylopectinosis/ Branching
Anderson’s
enzyme
disease
Accumulation of
highly branched
polysaccharide-limit
dextrin. Fasting
hypoglycemia
,hepatomegaly
Accumulation of
glycogen with few
branches .mild
hypoglycemia hepato
splenomegaly
39. Gluconeogenesis
Definition
The synthesis of glucose from non –
carbohydrate substrates.
Substrates
lactate
Glycerol
Glucogenic amino acids
Propionate
Sites:
Liver (90%) kidney (10%)
Sub cellular sites:
Partly mitochondrial & partly cytosolic
40. Significance of gluconeogenesis
1.Maintenance of blood glucose,when glycogen
stores are depleted.
-Tissues such as brain , RBC , require a
continous supply of glucose as a source of
energy . Liver glycogen meets these needs for
12-18 hrs .As the glycogen stores starts
depleting, gluconeogenesis ensures
continous supply of glucose to tissues .
2. removes the products of metabolism eg;
lactate produced in the muscle , propionate and
glycerol.
41. Death from alcohol overdose is due to
hypoglycemia due to reduced
gluconeogenesis!!!
42. Characteristics
Glycolysis and gluconeogenesis share the
same pathway but in opposite direction.
Gluconeogenesis utilizes all the seven
enzymes of glycolysis catalyzing reversible
reactions
Gluconeogenesis also utilizes four special
enzymes (the so called key enzymes of
gluconeogenesis) for catalyzing the reversal of
the three irreversible reactions of glycolysis
43. Glucose- 6- phosphatase is only present in
liver and kidney but not in the muscle. Thus
muscle cannot provide blood glucose by
gluconeogenesis.
44. Reactions of gluconeogenesis
1. Carboxylation of pyruvate to oxaloacetate
2. Transport of oxaloacetate to cytosol
3. Decarboxylation of cytosolic oxaloacetate
to phospho enol pyruvate (PEP).
4. Dephosphorylation of fructose -1,6bisphosphate to fructose-6- phosphate
5. Dephosphorylation of glucose -6phosphate to glucose
45. 1. Carboxylation of pyruvate to oxaloacetate
mitochondria
Pyruvate
ATP+CO2
biotin, Pyruvate carboxylase
ADP+Pi
mg2+
oxaloacetate
Cytoplasm
46. 2. Transport of oxaloacetate to cytosol
Oxaloacetate
Pyruvate
Malate dehydrogenase
oxaloacetate
NADH
Malate dehydrogenase
malate
malate
NAD+
Cytoplasm
Malate shuttle
48. 4. formation of fructose -1,6-bisphosphate by reversal of
glycolysis
Fructose-1,6-bisphosphate
Glyceraldehyde – 3- phosphate
Dihydroxy acetone
phosphate
1,3-bisphosphoglycerate
Cytoplasm
3-phosphoglycerate
2-phosphoglycerate
phosphoenolpyruvate
oxaloacetate
malate
Pyruvate
oxaloacetate
malate
49. 4. Dephosphorylation of fructose -1,6-bisphosphate to
fructose-6- phosphate
Fructose -6- phosphate
H2 O
Fructose- 1,6-bisphosphatase
Pi
Fructose-1,6-bisphosphate
Glyceraldehyde – 3- phosphate
Dihydroxy acetone
phosphate
1,3-bisphosphoglycerate
Cytoplasm
3-phosphoglycerate
2-phosphoglycerate
phosphoenolpyruvate
oxaloacetate
malate
Pyruvate
oxaloacetate
malate
50. 5. Dephosphorylation of glucose -6-phosphate to glucose
Glucose- 6- phosphatase is
only present in liver and
glucose- 6-phosphatase
kidney but not in the
muscle. Thus muscle
glucose-6- phosphate
cannot provide blood
glucose by gluconeogenesis.
Fructose -6- phosphate
glucose
Fructose-1,6-bisphosphate
Glyceraldehyde – 3- phosphate
Cytoplasm
Dihydroxy acetone
phosphate
1,3-bisphosphoglycerate
3-phosphoglycerate
2-phosphoglycerate
phosphoenolpyruvate
oxaloacetate
malate
Pyruvate
oxaloacetate
malate
54. Cori’s cycle
Cycle that operates between liver and muscle, for
efficient utilization of lactate
muscle
liver
glucose
glucose
gluconeogenesis
pyruvate NADH
LDH
glycolysis
blood
pyruvate +
NAD
Lactate dehydrogenase
NADH+H+
lactate
lactate
NADH+H+
55. Significance Of Coris Cycle
Lactate accumulation causes muscle cramps
during strenuous muscular exercise
Cori’s cycle prevents such excessive
accumulation of lactate and ensures
efficient reutilization of lactate by the body.
60. Regulation of gluconeogenesis
GLYCOLYSIS AND GLUCONEOGENESIS
ARE RECIPROCRALLY REGULATED.
Gluconeogenesis is regulated by the
following mehanisms:
1.Hormonal regulation (long term regulation)
2.Allosteric regulation (long term regulation)
61. Regulation of gluconeogenesis…
1.Hormonal regulation (long term regulation)
Induction by
-Glucagon,epinephrine,glucocorticoids
Repression by
-insulin
2.Allosteric regulation (long term regulation)
-Allosteric inhibition by AMP
-Allosteric activation by acetyl CoA