Metabolism of Carbohydrate

Metabolism of Carbohydrate
Dr. Uzma Zaman

Assistant Professor
Department of Biochemistry
DIMC, DUHS
Learning Objectives
 Discuss Digestion & Absorption of Carbohydrates
 Describe the Major and Minor Pathways for Oxidation
 Explain Glycolysis
 Describe Glycogenolysis
 Describe Gluconeogenesis
 Discuss Diabetes Mellitus

Digestion & Absorption of Carbohydrates
1-In the Mouth
Salivary amylase digests starch partially into mixtures of

dextrins and maltose.
2- In the Stomach
Salivary amylase acts for short time till the gastric HCL
inhibits the enzyme (due to drop of pH). Small amount of
acid hydrolysis occurs in stomach.
3- In the Small Intestine
a- Pancreatic amylase: It completes the digestion of starch

to maltose and isomaltose.
b- Intestinal disaccharidases :They complete the action of

other enzymes with production of monosaccharides e.g.
sucrase, maltase, lactase acting on sucrose, maltose,l
actose.
So, the end products of carbohydrate digestion are
mainly glucose, galactose and fructose.
 Monosaccharides actively absorbed by small intestine.
The portal vein carries simple sugars to the liver where

they are metabolized.
Liver does not consume all sugars passing through it, but
a large proportion of these sugars is delivered to systemic
blood in order to be utilized by other tissues.
Oxidation of glucose
A- The Major Pathways for Oxidation
which are mainly concerned with energy production.
I- Glycolysis: It produces pyruvate under aerobic condition

and lactate under anaerobic condition.
II- Citric acid cycle (Krebs’ cycle):Under aerobic condition,

pyruvate is converted to active acetate for oxidation
through citric acid cycle.
Oxidation of glucose
B-The Minor Pathways for Oxidation
which are mainly for synthesis of other glucose derivatives

and not for energy production.
I- Hexosemonophosphate pathway (HMP): For production

of pentoses and NADPH.
II- Uronic acid pathway: For production of uronic acids.

I-GLYCOLYSIS
 Sequence of enzymatic reactions in which one molecule

of glucose is converted into two molecules of three carbon
compound, either pyruvate in the presence of oxygen or
lactate in the absence of oxygen.
Glycolytic pathway proceeds in the cytosol of all cells (all

of the enzymes of glycolysis are found in the cytosol).
Glycolysisis also termed anaerobic oxidation of glucose as

it can proceed in the absence of oxygen.
Steps of Glycolysis can be divided into two phases:
Phase I
In this preparatory stage, glucose is phosphorylated

and cleaved to yield two molecules of glyceraldehyde 3-
phosphate. This process consumes 2 ATP.
Steps of Glycolysis can be divided into two phases:
Phase II
The two molecules of glyceraldehyde 3-phosphate

are converted to pyruvate under aerobic state with
generation of 4 ATP at substrate level and 6 ATP at the
respiratory chain level.
Under anaerobic state only 4 ATP are formed at the

substrate level with conversion of pyruvate to lactate.
Regulation of Glycolysis
Glycolysis is regulated at three nonequilibrium

(irreversible) reactions, i.e. 3 key enzymes:
I.Glucokinase(or hexokinase)
II.Phosphofructokinase-1(PFK-1)
III.Pyruvatekinase(PK).
II- CITRIC ACID CYCLE (Tricarboxylic Acid Cycle or Krebs' Cycle)
 It is formed of a series of reactions that are responsible for

the complete oxidation of the acetyl moiety of acetyl-CoA.
It is the final common pathway for the oxidation of

carbohydrates, lipids and proteins because glucose, fatty acids
and most amino acids are metabolized to acetyl-CoA or
intermediates of the cycle.
II- CITRIC ACID CYCLE
During the oxidation of acetyl-CoA, coenzymes (NAD and

FAD) are reduced and subsequently reoxidized in the
respiratory chain with the formation of ATP.
II- CITRIC ACID CYCLE
Site:
The enzymes of the TCA cycle are found in the

mitochondrial matrix except Succinate dehydrogenase
which is tightly bound to the inner mitochond rial
membrane (forms complex II of the respiratory chain).
The enzymes of the TCA cycle are in close proximity to

the enzymes of the respiratory chain.
B- The Minor Pathways for Oxidation
I- HexoseMonophosphate Pathway (HMP): The pentose
phosphate pathway (PPP) is an alternative route for glucose
oxidation. It has two major functions, formation of:
1) Ribose-5-p required for nucleotide and nucleic acid synthesis
2) NADPH
The enzymes of the pentose phosphate pathway are cytosolic.

HMP is active in certain tissues e.g. liver, thyroid, adrenal
cortex, adipose tissue, gonads, retina, lactating mammary
gland and RBCs.
NADPH
is required for the following reactions:
Reduction of metabolically important compounds as

glutathione and folic acid
Synthesis of fatty acids
Cholesterol synthesis
Hydroxylation reactions
Glutathione is of particular importance to combat

oxidation stress in tissues and to keep hemoglobin active by
conserving iron in ferrous state
II-Uronic Acid Pathway
It is also an alternative oxidative pathway for glucose that
does not lead to the formation of ATP.
It is a cytosolic pathway that occurs in the liver.
In humans, it catalyzes the conversion of glucose to
glucuronic acid, and pentoses.

II-Uronic Acid Pathway
The main function is the formation of UDP-glucuronate
which is utilized in the following pathways:
Glycosaminoglycans(GAGs) synthesis.
Conjugation reactions with many compounds to increase
their water solubility such as: all steroid hormones and their
metabolites, bilirubin and certain detoxification reactions of
xenbiotics such as phenols.

Glycogen Metabolism
Glycogen is a highly branched polymer of glucose. It is the
main storage form of carbohydrates in animals. It is
present mainly in the liver and in muscles.
• Liver glycogen (forms 8 – 10% of its wet weight)

maintains blood glucose between meals. After 12–18
hours of fasting, liver glycogen is almost totally depleted.
• Muscle glycogen(forms 2% of its wet weight) : supplies a
readily available source of glucose to the contracting
muscles
Glycogen metabolism includes the following:
I- Glycogenesis: is synthesis of glycogen from glucose-6-

p.this requires presence of the enzyme glycogen synthase.
II- Glycogenolysis: is breaking-down of glycogen to glucose

(in the liver) or to g-6-p (in the muscle)
Both glycogenesis and glycogenolysis are under strict

hormonal control mediated by a second messenger cyclic
AMP
GLUCONEOGENESIS
It is the synthesis of glucose and /or glycogen from non-
carbohydrate precursors e.g. glycerol, glucogenic amino
acids and lactate.
Its main function is to supply blood glucose in case of

carbohydrate deficiency (fasting, starvation and low
carbohydrate diet).
It starts 4 to 6 hours after the last meal and continues

throughout fasting state.
Regulation of Blood Glucose
The normal fasting plasma glucose level (after 8-12 hours
fasting) is between 70 to less than 100 mg/dL, increases after
meal and returns back to <140 mg/dL at two hours after feeding
(2 hour postprandial or 2h PP).
The maintenance of blood glucose is an important function of

different tissues. Glucose is the principal source for energy
production in the brain.
Sudden decrease in blood glucose if not treated may produce

coma or even death.
After-meal rise in blood glucose stimulates insulin secretion from
pancreatic β-cells of islets of langerhans.
Insulin action: It is secreted by the B-cells of pancreatic islets in
response to hyperglycemia. It produces its effects through the
following mechanisms:
It increases the uptake of glucose by extrahepatic tissues
(heart, skeletal muscles and adipose tissues).

It increases utilization of glucose (oxidation, glycogenesis and
lipogenesis) in different tissues.
It decreases output of glucose by liver (decreases
glycogenolysis and gluconeogenesis).

During fasting blood glucose decreases so insulin
secretion is inhibited whereas the anti-insulin
hormones increase leading to activation of mechanisms
of glucose production:
glycogenesis and gluconeogenesis.

Diabetes Mellitus
Definition
The term diabetes mellitus describes a metabolic disorder that

is characterized by persistent rise in blood glucose
(hyperglycemia) result from defects in insulin secretion, insulin
action, or both.
Classification of DM
Type I Diabetes Mellitus is primarily a disease of the young. It

was previously known as insulin dependent diabetes mellitus
(IDDM) it require insulin to control hyperglycaemia
Diabetes Mellitus
Type II Diabetes Mellitus It is previously known as
noninsulin dependent diabetes mellitus (NIDDM) means
that drugs stimulate endogenous insulin secretion and
promoting glucose utilization are required.
Metabolic Changes in DM
All the metabolic changes are due to decrease in the insulin /
anti-insulin ratio, which produces changes reversal to insulin
action or as a consequent of hyperglycemia.
1) Changes in carbohydrate metabolism include: This leads to

hyperglycemia, glucosuria, polyuria, loss of electrolytes,
dehydration, and polydepsia.
2) Changes in lipid metabolism include: Decreased lipogenesis

and increased lipolysis. This leads to weight loss and increases
plasma free fatty acids
Metabolic Changes in DM
3) Changes in protein metabolism include: it leads to increased
sensitivity to infection and delayed healing of wounds.
Complications of DM
These complications can occur over a long period of time.
They can be divided in macrovascular and microvascular
complications.
Diabetes accelerates atherosclerosis that can lead to

coronary artery disease, stroke and peripheral vascular
disease (macrovascular disease)
Damage to the retina (retinopathy), kidney (nephropathy)

and nerves (neuropathy) (microvascular disease).
Types of Diabetic Coma
I- Diabetic Ketoacidosis:
Diabetic ketoacidosis is considered a medical emergency
that results from uncontrolled hyperglycemia and
deficiency of insulin.
The condition can be precipitated by stress and infection.
Diabetic ketoacidosis is much more common in type I
diabetes, but can also occur in patients with type II
diabetes.
Types of Diabetic Coma
II- Hypoglycemic Coma
Hypoglycemia results from taking too much diabetes
medication or insulin.
It is manifested as headache, feeling dizzy, poor
concentration, tremors of hands, and sweating are
common symptoms of hypoglycemia. Coma occurs if blood
sugar level gets too low.

Diagnosis of DM
Many patients with diabetes remain asymptomatic for
long periods, so that the first presentation of the disease
is frequently a chronic complication.
Symptoms include polyuria, polydipsia, polyphagia,
prolonged time of wound healing, and weight loss.
Polyphagiaresults from the decreased glucose uptake
by the satiety centre in the brain.
Tests for Diagnosis and Assessment of DM Control
I- Fasting and 2-hour (post-glucose or postprandial) plasma
glucose levels in an oral glucose tolerance test (OGTT).
Non-diabetic healthy subjects will have:
Fasting plasma glucose < 100 mg/dL,
Two-hours value in an OGTT (2-h PG) < 140 mg/dL.
Patients with diabetes mellitus will have:
Fasting plasma glucose > 126 mg/dL,
2-hour value in an OGTT (2-h PG) at or above 200 mg/dL.

II- Oral Glucose Tolerance Test (OGTT) Normal OGTT: There is
an increase in plasma glucose levels after 30 and 60 minutes
from the glucose load due to the absorption of glucose
followed by a drop due to increased uptake and utilization of
glucose under the effect of the stimulated insulin secretion.
No glucosuria occurs during the test.

III- Measurement of Glycated- Hb (HbA1C):It is a good

for diagnosis and monitor of blood glucose to assess
diabetic control and to follow up of diabetic patients.
Normal HBA1C is 4 – 6.5%; levels above 6.5% are
diagnostic of diabetes mellitus and levels > 8 % indicate
poor diabetic control.
Treatment of Diabetes Mellitus
Diet control
It is to achieve weight reduction in overweight patients with

type II DM. If improvement in hyperglycemia is not
achieved by diet, trial with an oral drug should be started.
Oral Anti-diabetic Drugs:
These drugs are used for type II DM but not for type I DM
oral hypoglycemic drugs are: Drugs that increase insulin
secretion , improve insulin sensitivity or decrease the
intestinal absorption of carbohydrates and fats
Treatment of Diabetes Mellitus
Insulin:
Human insulin is now available in the market and often it is

preferred. It is injected subcutaneously, or as an insulin pen.
Recently, inhaled insulin is under trials.

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Metabolism of Carbohydrate

Dr. Uzma Zaman

 Describe the Major and Minor Pathways for Oxidation

 Discuss Diabetes Mellitus

Salivary amylase digests starch partially into mixtures of

a- Pancreatic amylase: It completes the digestion of starch

b- Intestinal disaccharidases :They complete the action of

 Monosaccharides actively absorbed by small intestine.

The portal vein carries simple sugars to the liver where

which are mainly concerned with energy production.

I- Glycolysis: It produces pyruvate under aerobic condition

II- Citric acid cycle (Krebs’ cycle):Under aerobic condition,

which are mainly for synthesis of other glucose derivatives

I- Hexosemonophosphate pathway (HMP): For production

II- Uronic acid pathway: For production of uronic acids.

 Sequence of enzymatic reactions in which one molecule

Glycolytic pathway proceeds in the cytosol of all cells (all

Glycolysisis also termed anaerobic oxidation of glucose as

In this preparatory stage, glucose is phosphorylated

The two molecules of glyceraldehyde 3-phosphate

Under anaerobic state only 4 ATP are formed at the

Glycolysis is regulated at three nonequilibrium

 It is formed of a series of reactions that are responsible for

It is the final common pathway for the oxidation of

During the oxidation of acetyl-CoA, coenzymes (NAD and

The enzymes of the TCA cycle are found in the

The enzymes of the TCA cycle are in close proximity to

1) Ribose-5-p required for nucleotide and nucleic acid synthesis

The enzymes of the pentose phosphate pathway are cytosolic.

is required for the following reactions:

Reduction of metabolically important compounds as

Synthesis of fatty acids

Glutathione is of particular importance to combat

It is also an alternative oxidative pathway for glucose that

does not lead to the formation of ATP.

It is a cytosolic pathway that occurs in the liver.

In humans, it catalyzes the conversion of glucose to

glucuronic acid, and pentoses.

The main function is the formation of UDP-glucuronate

which is utilized in the following pathways:

Conjugation reactions with many compounds to increase

metabolites, bilirubin and certain detoxification reactions of

xenbiotics such as phenols.

• Liver glycogen (forms 8 – 10% of its wet weight)

I- Glycogenesis: is synthesis of glycogen from glucose-6-

II- Glycogenolysis: is breaking-down of glycogen to glucose

Both glycogenesis and glycogenolysis are under strict

Its main function is to supply blood glucose in case of

It starts 4 to 6 hours after the last meal and continues

The maintenance of blood glucose is an important function of

Sudden decrease in blood glucose if not treated may produce

pancreatic β-cells of islets of langerhans.

Insulin action: It is secreted by the B-cells of pancreatic islets in

response to hyperglycemia. It produces its effects through the

It increases the uptake of glucose by extrahepatic tissues

(heart, skeletal muscles and adipose tissues).

lipogenesis) in different tissues.

It decreases output of glucose by liver (decreases

glycogenolysis and gluconeogenesis).

glycogenesis and gluconeogenesis.