CARBOHYDRATES
METABOLISM
MS. HAFSA MARYAM
LECTURER
UNIVERSITY OF LAHORE
Learning outcomes

Metabolism of Carbohydrates

Glycogenesis

Glycogenolysis

Gluconeogenesis

Blood Sugar Regulation
Glycogen metabolism Pathways

Glycogen is the storage form of glucose in animals

lt is stored mostly in Iiver (6-8%) and muscle (1-2%)

The function of liver glycogen is to maintain the blood glucose levels,
particularly between meals.

Muscle glycogen serves as a fuel reserve for the supply of ATP during
muscle contraction. Glycogen is the fuel reserve of the body because :

1. Glycogen can be rapidly mobilized

2. Glycogen can generate energy in the absence of oxygen

3. Brain depends on continuous glucose supply
Glycogenesis

The synthesis of glycogen from glucose. It takes place in the cytosol and requires ATP and UTP,
besides glucose.

Synthesis of UDP-glucose: Hexokinase( in muscle) and glucokinase(in liver) convert glucose to
G6P. Phosphoglucomutase catalyses the conversion of G6P to G1P.

Uridine diphosphate glucose (UDPG) is synthesized from glucose 1- phosphate and UTP by UDPglucose pyrophosphorylase.

Requirement of primer to initiate glycogenesis: A small fragment of pre- existing glycogen must act
as a 'primer’ to initiate glycogen synthesis.

Glycogen synthesis by glycogen synthase : Glycogen synthase helps in the formation of 1,4glycosidic linkages. Glycogen synthase transfers the glucose from UDP-glucose to the non-reducing
end of glycogen to form α-1,4 linkages.

Formation of branches in glycogen : Glucosyl α-4-6 transferase helps in branching and further
elongation
Glycogenolysis

It involves the degradation of stored glycogen in liver and muscle.

Glycogen is degraded by breaking α-1,4 and α-1,6-glycosidic bonds.

Irreversible pathway.

Action of glycogen phosphorylase: α-1,4-glycosidic bonds are cleaved by
glycogen phosphorylase to yield glucose 1-phosphate. This process
(phosphorolysis) continues until 4 glucose residues remain on either side of
branching point (α-1,6-glycosidic link).

The glycogen so formed is known as limit dextrin which cannot be further
degraded by phosphorylase.

Action of debranching enzyme : The branches of glycogen are cleaved by
debranching enzyme.

Glycosyl 4 : 4 transferase breaks α-1,4 glycosidic bonds

Amylo α-1,6-glucosidase breaks the α- 1,6 glycosidic bond.

Formation of glucose 6-phosphate and glucose : glucose 1-phosphate and free
glucose are produced in a ratio of 8 : 1 by the action of glycogen
phosphorylase and debranching enzyme. Glucose 1- phosphate is converted to
glucose 6 -phosphate by the enzyme phosphoglucomutase.

Glucose 6-phosphatase that cleaves G6P to glucose (in liver). This enzyme is
absent in muscle and brain
Glycogenolyis
Gluconeogenesis

The synthesis of glucose from noncarbohydrate compounds is known as
gluconeogenesis.

The major substrates/precursors for gluconeogenesis are lactate, pyruvate,
glucogenic amino acids, propionate and glycerol.

Gluconeogenesis occurs mainly in the cytosol, although some precursors are
produced in the mitochondria.

Gluconeogenesis mostly takes place in liver and kidney matrix.

The overall summary of gluconeogenesis for the conversion of pyruvate to glucose:

2 Pyruvate + 4ATP + 2GTP + 2NADH + 2H+ + 6H2O
+ 4ADP + 2GDP + 6Pi + 6H+
Glucose + 2NAD+
Significance:

Brain and central nervous system, erythrocytes, testes and kidney medulla are
dependent on glucose for continuous supply of energy. Human brain alone requires
about 120 g of glucose per day, out of about 160 g needed by the entire body.

Glucose is the only source that supplies energy to the skeletal muscle, under
anaerobic conditions.

In fasting even more than a day, gluconeogenesis must occur to meet the basal
requirements of the body for glucose and to maintain the intermediate of citric acid
cycle.

Certain metabolites produced in the tissues accumulate in the blood, e.g. lactate,
glycerol, propionate etc. Gluconeogenesis clears them from the blood
Blood sugar Regulation

Glucose Homeostasis: It is the maintenance of blood glucose level
within the normal range. The blood glucose level must be maintained
within the narrow limits of 70-100 mg/dl.

Normal blood glucose level (fasting) is 70-110mg/dl

Post-prandial blood glucose level is 120-140mg/dl.

Above and below the above level is consider as abnormal.

Hyperglycemia - Levels above the normal range

Hypoglycemia - Levels below the normal range
Homeostasis of blood glucose

High blood glucose - Beta cells release insulin

Low blood glucose - Alpha cells release glucagon

Normal blood glucose - Glycogenolysis in the liver; Glucose released to
blood Peripheral tissue Cells take glucose From blood
Fundamental Regulatory Mechanisms

As blood sugar tends to increase it stimulates the secretion of
insulin

Glycogenesis is accelerated

Utilization of glucose by tissues is increased

As blood sugar tends to decrease it stimulates the secretion of
glucagon, ratio of insulin/glucocorticoids and GH production of
glucose mainly by gluconeogenesis & glycogenolysis
Blood glucose regulation during Postprandial state Glucose

Insulin: Insulin is the first hormone to be isolated, purified, crystallized &
synthesized. Insulin secretion is associated with energy abundance.

Insulin: The insulin plays an important role in storing the excess energy. In the
case of excess carbohydrates, it causes them to be stored as glycogen mainly in
the liver and muscles. All the excess carbohydrates that cannot be stored as
glycogen are converted under the stimulus of insulin into fats and stored in the
adipose tissue.

Produced by beta cells of the pancreas. It is a small protein (with 51 AAs). It
has a molecular weight of 5808. It is composed of two polypeptide chains
connected to each other by disulfide linkages.
Role of hormones in glucose
Regulation

Hyperglycemic Hormones

Glucagon, Epinephrine or Adrenaline, Glucocorticoids, ACTH, Growth
hormone, Thyroxine All these are anti-insulin hormones.

Glucagon - produced by the α-cells of the islets of Langerhans of the
pancreas. Glucagon opposes the actions of insulin and increases Blood
Glucose

Epinephrine or Adrenaline: It is secreted by adrenal medulla and increases
blood glucose, promotes glycogenolysis and enhance gluconeogenesis

Glucocorticoids: It is secreted by adrenal cortex, increases blood glucose
and Enhance gluconeogenesis and releases AAs from muscle
Hypoglycemic hormone

Insulin: It is involve in glycogen synthesis

Gluconeogenesis

Uptake of glucose in muscle & adipose cells - Lipogenesis

Insulin acts at the transcriptional level to regulate synthesis of
more than 100 proteins.