CARBOHYDRATE
METABOLISM
By
Dr. Aisha Eid

METABOLISM OF FOODSTUFFS
Ptns, CHO, lipids
carbon compounds
CO2 & H2O
excretion

Dietary Carbohydrates:
 Monosaccharides:
glucose, fructose and galactose
in fruits and honey & obtained by hydrolysis of oligo- &
polysacs.
 Disaccharides:
sucrose, lactose, maltose (by hydrolysis of starch).
 Polysaccharides:
starch (in potatoes, rice, corn and wheat)
Cellulose (in cell wall of plants)
not digested by humans due to absence of cellulase

Digestion of Carbohydrates:
In the mouth:
Salivary amylase hydrolyzes starch into dextrin +maltose
In the stomach:
due to drop of pH salivary amylase acts for a very short time
In the small intestines:
Pancreatic and intestinal enzymes hydrolyze the oligo- and polysaccharides as
follows:
Pancreatic amylase
Starch maltose + isomaltose
Maltase
Maltose 2 glucose
Lactase
Lactose glucose + galactose
Sucrase
Sucrose glucose + fructose

Absorption of monosaccharides:
1. Simple diffusion:
Depending on the concn gradient of sugars between
intestinal lumen and mucosal cells.
e.g. Fructose and pentose
2. Facilitated transport:
It requires a transporter.
e.g. Glucose, Fructose and galactose
3. Active transport (cotransport):
It needs energy derived from the hydrolysis of ATP.
glucose & galactose are actively transported against
their concentration gradients by this mechanism.

Fate of absorbed monosaccharides:
In the liver, fructose and galactose are converted to
glucose. Fate of glucose:
A. Uptake by different tissues (by facilitated diffusion)
B. Utilization by the tissues: in the form of:
1. Oxidation to produce energy:
- Major pathways (glycolysis & Krebs' cycle).
- Minor pathways (hexose monophosphate pathway & uronic acid pathway)
2. Conversion to other substances:
Carbohydrates: ribose (RNA,DNA), galactose (in milk), fructose (semen)
Lipids: Glycerol-3 P for formation of triacylglycerols.
Proteins: Non-essential amino acids which enter in formation of proteins.
C. Storage of excess glucose:
as glycogen in liver and muscles,
when these reserves are filled it is converted to TAG & deposited in adipose tissue.
D. Excretion in urine
If blood glucose exceeds renal threshold (180 mg/dL), it will be excreted in urine.

Glucose Oxidation
Extracting Energy from Glucose:
There are 3 major biochemical processes that occur in
cells to progressively breakdown glucose with the
release of various packets of energy:
Glycolysis (occurs in the cytoplasm and is only
moderately efficient).
Krebs' cycle (takes place in the matrix of the
mitochondria and results in a great release of
energy).
Electron transport chain.

GLUCOSE OXIDATION

GLYCOLYSIS
Series of biochemical reactions by which
glucose is converted to:
-Pyruvate (in aerobic conditions)or
-Lactate (in anaerobic conditions).
Site: cytosol of every cell.
Physiologically it occurs in:
-muscles during exercise (lack of oxygen)
-RBCs (no mitochondria).

Steps:
Phase one: 1 molecule of glucose (C6) is converted to 2
molecules of glyceraldehyde 3-phosphate (C3)
as follows:
ATP ATP
Glucose (C6) 2 Glyceraldehyde 3 P (C3)

Phase two: in this phase the 2 molecules of glyceraldehyde 3-P
are converted to 2 molecules of pyruvate (aerobic)
or lactate (anaerobic):
4 ATP
2 Glyceraldehyde-3 P (C3) 2 Pyruvic Acid (C3)
2 NADH + 2 H+
2 NAD+
2 Lactic Acid

Overall, glycolysis can thus be summarized as
follows:
Glucose 2 Pyruvic Acid + 2 net ATP
+4 hydrogens (2 NADH2)
2 Lactic Acid + 2 net ATP

Regulation of Glycolysis:
It can be noted that all reactions of glycolysis
are reversible except those catalyzed by:
 Glucokinase (or hexokinase) (GK)
 Phosphofructokinase (PFK)
 Pyruvate kinase (PK)
Glycolysis is regulated by factors which
control the activity of the key enzymes
which catalyze the 3 irreversible
reactions.

Activity of these enzymes increase during CHO
feeding, and decreases during starvation:
 Regulation according to energy
requirements of cell
 Regulation by hormones

Regulation according to energy
requirements of cell:
Each cell regulates glycolysis according to
the rate of utilization of ATP:
i) High levels of AMP
(indicating high ATP utilization):
+++ PFK (i.e. activates glycolysis).
ii)High levels of ATP
(indicating little utilization of ATP):
- - -PFK and PK (i.e. inhibits glycolysis).

Regulation by hormones:
Postprandial hyperglycemia causes:
+++ of insulin
--- glucagon & adrenaline (anti-insulin hormones)
i) Insulin:
+++ all pathways of glucose utilization.
+++ glycolysis by inducing synthesis, activation
of all the glycolytic key enzymes (GK, PFK, PK).
ii) Glucagon:
Inhibits glycolysis by acting as
repressor & inactivator of the glycolytic key enzymes.

Importance of Glycolysis:
1. Glycolysis provides mitochondria with pyruvic a
oxaloacetate which is the primer of the Krebs' cycle.
2. Glycolysis provides dihydroxyacetone P glycerol 3-P
that is important for lipogenesis (TAG synthesis)
3. Energy production:
Glycolysis liberates only a small part of energy from
glucose, however:
a. Important during severe muscular exercise, where
oxygen supply is often insufficient to meet the
demands of aerobic metabolism.
b. Provides all energy required by the R.B.Cs. (due to
lack of mitochondria).

Energy yield of glycolysis:
In absence of oxygen:
2 ATP are consumed for conversion of glucose
to Fructose 1,6 P.
2 ATP are produced during conversion of
glyceraldehydes 3-P to pyruvate.
Since 1 glucose molecule gives 2 molecules of
G 3-P, then total number of ATP produced is 4.
net gain of ATP in absence of oxygen is:
4-2=2 ATP.

Energy yield of glycolysis:
In presence of oxygen:
2 ATP are produced directly
(as in absence of oxygen),
6 ATP are produced indirectly:
from oxidation of 2 NADH2 through ETC
net gain of ATP in presence of oxygen is:
2+6= 8 ATP.

The Transition Reactions
These link glycolysis to the Krebs Cycle
Alternate Fates of Pyruvate
A. Oxidative Decarboxylation B. Carboxylation
forms Acetyl CoA forms Oxaloacetate

Oxidative decarboxylation of pyruvate:
Puruvate dehydrodenase complex irreversibly converts
pyruvate into acetyl CoA:
Pyruvic acid (3C)+NAD++Coenzyme A
Acetyl CoA(2C)+CO2+ NADH+ H+
Acetyl CoA can also be produced by breakdown of:
 lipids or
 certain (ketogenic) amino acids.
-NAD+ is converted into NADH+H+.
Those hydrogens go through oxidative phosphorylation and
produce 3 more ATP.

Oxidative decarboxylation of pyruvate:
NADH+H
2 CoA
NADH+H

Carboxylation of pyruvate to oxaloacetate:
Pyruvate carboxylase converts
pyruvate to oxaloacetate.
Pyruvic acid (3C) + CO2 + ATP
Oxaloacetic acid (4C) + ADP + Pi

Finally, comes the Krebs' Cycle
Krebs' Cycle
(Citric Acid Cycle)
(Tricarboxylic Acid Cycle)
"TCA"

Site: mitochondria of every cell
Series of biochemical reactions that are
responsible for complete oxidation of
CHO, fats and Ptns to form :
CO2 + H2O + Energy

Steps:
acetyl-CoA + oxaloacetate citrate

+H+
+H+
+H+
+H+
Acetyl CoA
oxaloacetate
× 2

During this process the following is
produced:
 3x2=6 NADH+H+
 1x2=2 FADH2
 1x2=2 ATP
 2x2=4 CO2

Each glucose molecule that goes through Krebs cycle
+ the preparatory conversion to Acetyl CoA gives:
 8 NADH
 2 FADH2
 2 ATP
 6 CO2
N.B.: glycolysis produced 2 ATP + 2 NADH,
so there is a net production of:
 4 ATP
 10 NADH

Energy yield of Krebs' cycle:
Glucose 2 puruvate
2 NADH
2 oxaloacetate
4 ATP
6 ATP
6 ATP
6 ATP
6 ATP

Energy yield of Krebs' cycle:
1 mole of acetyl CoA through Krebs' cycle produces 12 ATPs:
1 ATP (substrate level oxidative phosphorylation).
1 FADH2 → 2 ATP (respiratory chain oxidative phosphorylation).
3 NADH+H+→9 ATP(respiratory chain oxidative phosphorylation)
oxidative decarboxylation of pyruvate gives 1 NADH+H+ → 3 ATP
Thus net ATP gain is: 12 + 3 = 15 ATP
Since 1 glucose molecule by undergoing glycolysis gives 2 pyruvate
Thus 1 glucose molecule yields 15 × 2 = 30 ATP.

Thus complete oxidation of glucose
(in presence of oxygen) gives:
 Glycolysis: 8 ATP
 Total ATP yield = 30+8 = 38 ATP.

2 Acetyl CoA
Reduced coenzymes (e-)
10 NADH + 2 FADH2
38

Regulation of Krebs' cycle:
1. Regulation according to energy status of the cell:
+++NADH/NAD and ATP/ADP (thus no need for further energy
production) inhibit the cycle, and vice versa.
Krebs' cycle is only aerobic, since under anaerobic conditions the
respiratory chain is inhibited leading to increased NADH/NAD
ratio which inhibits the cycle.
2. Regulation according to availability of substrate:
+++ acetyl CoA and oxaloacetate +++ cycle.
+++ intermediate products of cycle (citrate & succinyl Co A)
---feedback inhibition of the cycle.

Importance of Krebs' cycle:
1. Energy production: 1 acetyl CoA yields 12
ATP.
2. It is the final common metabolic pathway for
complete oxidation of acetyl CoA which
results from the partial oxidation of CHO, fats
and proteins (amino acids).
3. Interconversion of carbohydrates, fats and
proteins (gluconeogenesis, lipogenesis, and
formation of non-essential amino acids).

Minor Pathways of Glucose Oxidation:
 Hexose monophosphate pathway
(HMP shunt).
 Uronic acid pathway.

Hexose Monophosphate Pathway
(HMP shunt)
Pentose Phosphate Pathway
Pentose Shunt
Site: cytoplasm of cells e.g. liver, adipose
tissue,
adrenals, gonads, RBCs and retina.
Steps:
Glucose-6-P dehydrogenase
G-6-P R-5-P
NADP+ CO2 NADPH+H+

Importance of HMP shunt
R-5-P NADPH
Importance
for RBCs

Importance of HMP shunt:
2. It is the main source of NADPH:
coenzyme for reductases, hydroxylases and NADPH oxidase
which catalyze several important biochemical reactions, e.g.:
i) Fatty acid synthesis lipogenesis:
HMP is active in liver, adipose tissue & lactating memory gland.
ii) Steroid synthesis:
HMP is active in adrenal cortex, testis, ovaries and placenta.
iii) Important for vision:
NADPH
retinal retinol (important for vision)
Thus HMP is active in the eye.

3) Importance of HMP in RBCs:
-H2O2 (powerful oxidant) produces damage of:
 cellular DNA,
 Ptns
 phospholipids of cell membrane.
-RBCs are liable to oxidative damage by H2O2 due to
their role in O2 transport.
-H2O2 produces oxidative damage in the form of:
 Oxidation of Fe2+ to Fe3+ (metHb can’t carry O2)
 Lipid peroxidation which increases cell membrane
fragility.
RBC lysis + anemia & jaundice

HMP in RBCs produces NADPH, which
provides reduced GSH to remove H2O2
protects cell from oxidative damage
GSH reductase & GSH peroxidase remove
H2O2 produced by biochemical reactions:

glutathione peroxidase
H2O2 2 H2O
2 G-SH G-S-S-G
NADP+ NADPH, H+
glutathione reductase

Favism:
 Genetic condition due to deficiency of
(G6PD),
 There is impaired HMP in the RBCs, and
RBC capacity to protect itself from oxidative
damage is markedly decreased (--- NADPH)
 Eating Fava beans (which contain oxidizing
agents), or administration of certain drugs
(e.g. aspirin, sulfonamides or primaquin)
which stimulate production of H2O2, produce
lysis of the fragile red cells.

Regulation of HMP:
 NADPH produces feedback (-) G6PD.
 Insulin produces (+) G6PD.
N.B:
Insulin produced in response to
hyperglycemia
increase glucose oxidation by HMP
( acts as inducer of synthesis of G6PD).

Uronic Acid Pathway
This pathway converts glucose to glucuronic acid.
Site: cytosol of liver cells.
Importance of Uronic Acid Pathway:
enters in different biological reactions, e.g.:
1. Synthesis of glycosaminoglycans (GAGs).
2. Conjugation with certain compounds rendering
them more water soluble, thus helping in their
excretion, e.g.:
 Steroid hormones.
 Bilirubin, which is excreted in bile in the form of
bilirubin diglucuronide.

Glycogen Metabolism
Glycogenesis
Glycogenolysis
Gluconeogenesis

Glycogen Metabolism
1. Liver glycogen:
-Forms 8-10% of the wet weight of the liver.
-Maintains blood glucose (especially between meals).
-Liver glycogen is depleted after 12-18 hours fasting.
2. Muscle glycogen:
-Forms 2% of the wet weight of muscle.
-Supplies glucose within muscles during contraction.
-Muscle glycogen is only depleted after prolonged
exercise.

Glycogen metabolism includes:
 Glycogenesis: synthesis of glycogen
from glucose.
 Glycogenolysis: breakdown of
glycogen to glucose-1-phosphate.
 Gluconeogenesis: synthesis of
glucose or glycogen from non-CHO
precursors.

Glycogenesis & Glycogenolysis
Site: cytoplasm of liver and muscles.
The key enzyme of glycogenesis is glycogen synthase.
The key enzyme of glycogenolysis is glycogen phosphorylase.
In muscles: G-6-P is oxidized by glycolysis to provide energy
during muscle contraction.
In liver:
G-6-Phosphatase
G-6-P Glucose + Pi Blood G
N.B: Muscles cannot supply blood glucose due to their lack
of the enzyme G-6-phosphatase.

Glycogenesis
Glycogenolysis
Glycogen Synthase
+ Branching Enzyme
Glycogen
Phoshorylase
hexokinase

Mechanism of glycogen
synthesis (glycogenesis):
A. Synthesis of UDP-glucose.
B. Synthesis of a primer to initiate glycogen synthesis:
A fragment of glycogen (present in cells whose glycogen stores are
not totally depleted) can serve as a primer.
C. Elongation of glycogen chains by glycogen synthase:
-Glycogen synthase uses UDP-glucose to add glucose to
glycogen primer (1,4 link), and the process is repeated.
D. Formation of branches in glycogen:
-When the chain becomes about 6-11 glucose units long, the
branching enzyme transfers 5-8 glucosyl residues of α-1,4-
chain to a neighboring chain attaching it by α-1,6- glucosidic
linkage

Mechanism of glycogen
degradation (glycogenolysis)
A. Shortening of chains:
Glycogen phosphorylase acts on the 1,4-glucosidic linkage of
glycogen G-1-P residues
until each branch contains only 4 glucose units.
B. Removal of branches:
-The transferring enzyme transfers 3 glucose units from one end
of the short branch to the end of another branch.
-The debranching enzyme cleaves 1,6-glucosidic linkage
releasing free G , and the process is repeated.
C. Conversion of G-1-P to G-6-P:
This is done by phosphoglucomutase enzyme.

Regulation of Glycogen
Synthesis vs. Degradation
Glycogen synthase & glycogen phosphorylase: key enzymes
Regulation of these enzymes occurs via:
 Covalent modification (phosphorylation & dephosphn.)
 Allosterics
 Hormones
-Reciprocal control of the two pathways is hormonally
mediated through phosphorylation and
dephosphorylation of synthase and phosphorylase.
-Phosphorylation of enzymes :
turns synthesis off (--- glycogenesis), and
turns degradation on (+++ glycogenolysis).

Covalent modification :
Phosphorylation/dephosphorylation
I. Glycogen synthase is present in two forms:
a-form: it is the active form and it is dephosphorylated.
b-form: it is the inactive form and it is phosphorylated.
-Conversion of a- to b-form by protein kinase: ++ by c-AMP
-Conversion of b- to a-form by protein phosphatase.
II. Glycogen phosphorylase is present in two forms:
a-form: it is the active form and it is phosphorylated.
b-form: it is the inactive form and it is dephosphorylated.
-Conversion of a- to b-form by the enzyme protein phosphatase.
-Conversion of b- to a-form by phosphorylase kinase:+by c-AMP

Allosteric regulation:
Conformational changes in the enzyme ptns affecting activity and regulation:
 Glucose-6-phosphate
++ synthase (+) glycogenesis (excess substrate).
- - phosphorylase (-) glycogenolysis & (+) glycogenesis.
 ATP
+ + synthase (+) glycogenesis
- - phosphorylase (-) glycogenolysis
.
 Ca+2
++ phosphorylase kinase (+) glycogen phosphorylase glycogenolysis
-Muscle contraction ---> Ca+2 release (+) phosphorylase glycogenolysis
(+) glucose ATP generation for ensuing cycles of muscle contraction.

Hormonal regulation

Insulin:
++ phosphodiesterase - cAMP - protein kinase
++ protein phosphatase
A. stimulates glycogenesis:
b- a-form of glycogen synthase (activation)
activation of glycogenesis in both liver and muscle.
B. inhibits glycogenolysis:
a- b-form of glycogen phosphorylase (inactivation)
This leads to inactivation of glycogen phosphorylase
(conversion of active to the inactive form)
decrease glycogenolysis in both liver and muscle.

Insulin
+++Glycogenesis ----Glycogenolysis

B. Glucagon (in liver) and
epinephrine (in liver and muscles):
Both hormones produce activation of adenyl cyclase thus
increasing cAMP
This produces activation protein kinase.This converts:
1. Active a- to inactive b-form of glycogen synthase
(phosphorylated), thus inhibiting synthase.
Accordingly glucagon & epinephrine --- glycogenesis.
2.Inactive b- to active a-form of glycogen phosphorylase,
thus activating glycogen phosphorylase.
Accordingly glucagon & epinephrine +++glycogenolysis.

C. Growth hormone and
glucocorticoids:
+++ gluconeogenesis +++ G-6-P
G-6-P allosterically +glycogen synthase-b
++glycogenesis.
Thus growth hormone &
glucocorticoids
activate glycogenesis.

Regulation according to
nutritional status:
A. In the well fed state:
Glycogen synthase is allosterically (+) by G6P (which
is present in high concentrations).
Glycogen phosphorylase is (-) by G6P & ATP, i.e.
(-)glycogenolysis & (+)glycogenesis stores bl glucose
B. During starvation:
There are decreased levels of G6P & ATP, thus
(-)glycogenesis & (+)glycogenolysis to supply blood
glucose.

Muscle glycogen and blood
glucose
Muscle glycogen can be converted to
Bl glucose via indirect pathways:
Cori's cycle:
during muscle exercise
Glucose- alanine cycle:
during starvation

Cori's cycle:
glycolysis
gluconeogenesis
Glycogen

Glucose- alanine cycle:
gluconeogenesis
transamination
Glycogen

Glycogen storage diseases:
Inherited deficiencies of specific enzymes of
glycogen metabolism.
Von Gierke's disease (most common)
Cause: deficiency of G-6-phosphatase.
It is characterized by:
-enlargement of liver and kidneys
-hypoglycemia
-hyperlipemia
-hypercholestorelemia.

Gluconeogenesis

Gluconeogenesis
Synthesis of glucose from non-carbohydrate
precursors.
These precursors are metabolic intermediates.
Importance:
Supply blood glucose in case of CHO deficiency
>18 hrs. (fasting, starvation and low CHO diet).
Site:
Cytosol of liver cells
and to a lesser extent in kidneys.

Steps:
By reversal of glycolysis.
3 glycolytic key enzymes are reversed by
4 key enzymes of gluconeogenesis
as follows:

Glucogenic Precursors:
They give directly or indirectly pyruvate,
oxaloacetate or any intermediates of
glycolysis or Krebs' cycle. They include:
1. Lactate:
It is released by R.B.Cs. and by skeletal muscles
during exercise, then transferred to the liver
to form pyruvate then glucose.
2. Glycerol:
It is produced from digestion of fats and from
lipolysis.

3. Glucogenic amino acids:
Ptns are the main sources of blood glucose especially after 18 hrs
due to depletion of liver glycogen.
-Some amino acids by deamination directly form pyruvic acid or
oxaloacetic.
-Others may give intermediates of Krebs' cycle which go through
the cycle eventually yielding oxaloacetic acid.
4. Propionyl CoA:
Many amino acids may give propionyl CoA through their
catabolism. Also the last 3 carbons of odd chain fatty acids form
propionyl CoA and thus give glucose. This is uncommon in
humans.

Regulation of gluconeogenesis:
Gluconeogenic regulatory key enzymes are those which
reverse the glycolytic key enzymes.
Glycolysis and gluconeogenesis are reciprocally controlled:
Insulin:
(secreted after carbohydrate meal)
--- gluconeogenic key enzymes (at the same time it acts as inducer
of glycolytic key enzymes) decrease bl. Glucose.
Anti-insulin hormones (glucagon, epinephrine,
glucocorticoids & growth hormone):
(secreted during fasting, stress or severe muscular exercise)
+++ gluconeogenic key enzymes, thus increasing gluconeogenesis
increased blood glucose.

Blood Glucose
Concentration of bloog glucose:
fasting blood glucose (8-12 hrs. after the last meal) is
70-110 mg/dL.
It increases after meals but returns to fasting level
within 2 hrs.
Sources of blood glucose:
Dietary carbohydrates.
Glycogenolysis (during fasting for less than 18 hrs.).
Gluconeogenesis (during fasting for more than 18 hrs.).

Regulation of Blood Glucose:
Four factors are important for regulating
blood glucose level:
I. Gastrointestinal tract.
II. Liver
III. Kidney.
IV.Hormones.

I. Gastrointestinal tract:
1. It controls the rate of glucose absorption.
The maximum rate of glucose absorption is
1 gm/kg body weight/ hour.
An average person weighing 70 gm will absorb
70 gm glucose/ hour.
2. Glucose given orally stimulates more insulin
than intravenous glucose. This may be due to
secretion of glucagon-like substance by
intestines. This stimulates B-cells of pancreas
to secrete more insulin. This is called
anticipatory action.

II. Liver:
The liver is the main blood glucostat
Maintains blood glucose level within normal as follows:
A. If blood glucose level increases, the liver controls this
elevation and decreases it through:
1. Oxidation of glucose via major and minor pathways.
2. Glycogenesis.
3. Lipogenesis.
B. If blood glucose level decreases, the liver controls this
drop and increases it through:
1. Glycogenolysis.
2. Gluconeogenesis.

III. Kidney:
All glucose in blood is filtered through the
kidneys, it then completely returns to the
blood by tubular reabsorption.
If blood glucose exceeds a certain limit (called
renal threshold), it will pass in urine causing
glucosuria.
Renal threshold: it is the maximum rate of
reabsorption of glucose by the renal tubules.
Normally the renal threshold for glucose is
180 mg/100mL.

IV. Hormones:
A. Insulin (the only hypoglycemic hormone):
Action of insulin:
Insulin decreases bl glucose level by:
1. +++ oxidation of glucose
2. +++ glycogenesis
3. --- glycogenolysis
4. --- glyconeogenesis
5. +++ lipogenesis

B. Anti-Insulin Hormones:
(hyperglycemic hormones):
1. Growth Hormone:
It elevates the blood glucose level by stimulating gluconeogenesis.
2. Thyroxine:
It elevates the blood glucose level by:
Increasing the rate of absorption of glucose from intestines.
Stimulating gluconeogenesis and glycogenolysis.
Inhibiting glycogenesis.
3. Epinephrine (adrenaline):
It increases the blood glucose level by increasing glycogenolysis in
both liver and muscles.
4. Glucagon:
It increases the blood glucose level by increasing glycogenolysis in
liver only.

Mechanism of Blood Glucose
Regulation
(Glucose Homeostasis)
The blood glucose level is regulated by the balance between the
action of insulin and anti-insulin hormones (hyperglycemic
hormones).
After a carbohydrate meal:
Bl glucose increases, stimulating the secretion of insulin which
tends to decrease the blood glucose level by its various actions.
During fasting:
Bl glucose is low; this stimulates the secretion of the anti-insulin
hormones (hyperglycemic hormones) which by their various
mechanisms lead to increasing the blood glucose level.
The net result is a condition of glucose equilibrium, or what
we call the homeostatic mechanism.

Abnormalities of Blood
Glucose Level
These may be in the form of:
 Hyperglycemia
 Hypoglycemia
Hyperglycemia: (Diabetes Mellitus):
It is due to:
decreased insulin secretion and/or
hypersecretion of anti-insulin hormones.

Hypoglycemia:
-It is the decrease in blood glucose level below the fasting level.
At a level of 50mg/100 mL convulsions occur
At a level of 30 mg/100 mL coma and death result.
-Hypoglycemia is more dangerous than hyperglycemia
because glucose is the only fuel to the brain.
Causes:
i. Excess insulin:
a) Overdose of insulin.
b) Tumor of B-cells of pancreas (insulinoma).
ii. Hyposecretion of anti-insulin hormones:
(hypo-functions of the pituitary gland, adrenals & thyroid gland).
insulin acts unopposed causing lowering of blood glucose
iii. Liver disease:
hypoglycemia is due to decreased glycogen stores and impaired
gluconeogenesis.

Glucosuria
Presence of detectable amounts of glucose in urine (>30 mg/dL).
Causes:
A. Hyperglycemic glocusuria:
Bl glucose exceeds the renal threshold (180mg/dL). It is caused by:
1. Diabetes mellitus.
2. Emotional or stress glucosuria (epinephrine glucosuria)
3. Alimentary glucosuria;It is due to increased rate of glucose
absorption as in cases of gastrectomy or gastrojejunostomy.
B. Normoglycemic or renal glucosuria:
1. Congenital renal glucosuria (diabetes innocens):
due to congenital defect in renal tubular reabsorption of glucose.
2. Acquired renal disease (e.g. nephritis).
3. Pregnancy glucosuria:
It appears during pregnancy and disappears later on after labour.