Metabolism of Carbohydrates

Metabolism of Carbohydrates

Glycogen Metabolism

Types of hormones

Glucagon: produced by the pancreas when blood glucose is lowInsulin: produced by the pancreas when blood glucose is highEpinephrin: released by the adrenal glands, high exerciseGlucocorticoids (cortisol) – steroid hormone released by the adrenal glands

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)

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+

Glucose

Glycogen
Glucose-6-phosphate
Pyruvate
Glycolysis OFF
Gluconeogenesis ON
Glycogenolysis ON
Glycogenolysis ON
Glycolysis ON
Glycogen
Glucose-6-phosphate
Pyruvate
Glucose
Muscle Epinephrin (cAMP)
Liver Glucagon,epinephrin (cAMP)
Gluconeogenesis Very little occurs in muscle
Does NOT occur In muscle !
Glycolysis and Gluconeogenesis – regulation – hormonal During stravation, Cortisol, promotes gluconeogenesis, protein breakdown in muscle, supplies amino acids to the liver.


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

Glycogen Metabolism - synthesis

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

(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 Glycogen Metabolism – breakdown (glycogenolysis)

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

Insulin

Produced in pancreas -  Blood glucose level Blood glucose normal range 3.3 - 7 mMbalance maintained between:glucose utilisation - glycolysis, synthesis of glycogen and fatty acidsb) glucose production - gluconeogenesis and glycogen breakdown.All of the above pathways are subject to hormonal control.

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. Insulin



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.