1. Metabolism of Carbohydrates
Glycogen Metabolism

2. Types of hormones
Glucagon: produced by the pancreas when blood glucose is low
Insulin: produced by the pancreas when blood glucose is high
Epinephrin: released by the adrenal glands, high exercise
Glucocorticoids (cortisol) – steroid hormone released by the adrenal glands
The types of hormones that we will talk about today; keep in mind the condition sunder which they are released throughout the lecture; things will make more sense that way.

3. Control of glucose uptake
Glucose needs specific transporters to enter the cells
In Brain, liver and RBC NOT Insulin dependent
In Muscle and adipose cells Insulin dependent
3. Once taken inside the cell, the first step is Phosphorylation
(hexokinase or glucokinase)
Glucose needs specific transporters to be taken up inside the cell, once you have high glucose levels, the cells sense this and they send more transporters to the membrane to take it up. Different organs have different sensitivities due to the presence of the sensor (transporter) inside the cells. Once inside the cell, glucose is phosphorylated that makes it stuck inside the cell now.

4. Gluconeogenesis - overview
Metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, pyruvate, glycerol, and glucogenic amino acids.
To supply Brain, RBC, exercising muscle, etc.
It takes place in the liver and to a lesser extent in the cortex of the kidneys.
Occurs during periods of fasting, starvation or intense exercise
Sum reaction:
2 pyruvate + 4 ATP + 2 GTP + 2NADH + 6H2O
 glucose +2 NAD+ + 4 ADP + 2 GDP + 6 Pi + 4 H+

5. Glycolysis and Gluconeogenesis – regulation – hormonal
Liver
Glucagon,epinephrin
(cAMP)
Glycogen
Glucose-6-phosphate
Pyruvate
Glucose
Muscle
Epinephrin
(cAMP)
Glucose
Glycogen
Glucose-6-phosphate
Pyruvate
Glycogenolysis ON
Glycogenolysis ON
Gluconeogenesis
Very little occurs in muscle
Does NOT occur
In muscle !
Glycolysis OFF
Glycolysis ON
Gluconeogenesis ON
the signal for the liver to make more blood glucose is GLUGAGON: activates glycogen breakdown and gluconeogenesis. Glycolysis needs to be inhibited cuz you don't want to activate glucose breakdown and synthesis at the same time.
In Muscle, no receptor for glucagon, epinephrine results in an increase in cAMP designed to increase ATP production. So turn ON glycogen breakdown, and logically would turn ON glycolysis to generate more ATP
During stravation, Cortisol, promotes gluconeogenesis, protein breakdown in muscle, supplies amino acids to the liver.

6. Glycogen Metabolism - overview
- Functions as energy storage in animal cells: In liver and muscle
Skeletal muscle - ~400g glycogen (1-2% weight)
Liver - ~100g glycogen (6-8% weight)
Glycogen exists in cytoplasmic granules that contain enzymes
for its synthesis and breakdown
Liver glycogen
 during well-fed state,
 during fasting.
Muscle glycogen only moderately
depleted during prolonged
fasting.
Glycogen granules in liver cells

7. Glycogen Metabolism - synthesis
glucose-6-P
glucose
HK or GK
glucose-1-P
phosphoglucomutase
UTP
UDP-glucose + PPi
(UDP-l)
UDP-glucose pyrophosphorylase
-O-l-l-l-l
UDP
-1,4 bonds {
glycogen synthase
-O-l-l-l-l-l-l-l-l-l-l
-l-l-l-l
Transferase
-1,6 bond

8. Glycogen Metabolism – breakdown (glycogenolysis)
(glucose)n
l-l-l-l-l-l-l-l-l~
Glucose-1-P + l-l-l-l-l-l-l-l~ Pi
(glucose)n-1
glycogen phosphorylase
phosphoglucomutase
Glucose-6-P
Note:
free glucose is released from each -1,6 linked residue
degradation of branch points requires 2 further enzymes

9. Glycogen Metabolism – regulation
Liver ( maintains BGL ):
Well fed state:
Glycogen synthesis
During fasting:
Glycogen breakdown
Skeletal muscle
During exercise:
During rest:
Regulation is complex - controlled by enzyme activation
and hormones

10. Insulin Produced in pancreas -  Blood glucose level
Blood glucose normal range mM
balance maintained between:
glucose utilisation - glycolysis, synthesis of glycogen and fatty acids
b) glucose production - gluconeogenesis and glycogen breakdown.
All of the above pathways are subject to hormonal control.

11. Insulin
When blood glucose  - insulin is secreted -  rate of glucose uptake in liver and peripheral tissues  plasma glucose  - when this falls below a critical value - insulin secretion  - glucagon secreted, therefore the insulin/glucagon is critical in maintenance of blood glucose level.
Diabetes is characterised by abnormally  blood glucose level and intolerance to ingested glucose.

13. Insulin and diabetes
Type I – Juvenile onset – insulin-dependent: autoimmune attack on insulin producing cells in the pancreas, so insulin production is deficient. Responds to insulin injection.
Type II – non-insulin dependent: insulin levels may be normal, but the cells are insensitive due to a down regulation of the insulin receptors. Usually onset occurs after age 35, frequently associated with obesity.