!!!Glycolysis, neoglucogenesis, the anaerobic degradation of glucose
DIGESTION OF CARBOHYDRATES
Glycogen, starch and disaccharides (sucrose,
lactose and maltose) are hydrolyzed to
monosaccharide units in the gastrointestinal tract.
The process of digestion starts in the mouth by the
salivary enzyme α –amilase.
The time for digestion in mouth is limited.
Salivary α -amilase is inhibited in stomach due to the
action of hydrochloric acid.
Another α -amilase is produced in pancreas and is
available in the intestine.
α -amilase hydrolyzes the α -1-4-glycosidic
bonds randomly to produce smaller subunits like
maltose, dextrines and unbranched
The intestinal juice contains enzymes hydrolyzing
disaccharides into monosaccharides (they are produced
in the intestinal wall)
Sucrase hydrolyses sucrose into glucose and
lactose into glucose
maltose into two
ABSORPTION OF CARBOHYDRATES
Only monosaccharides are absorbed
The rate of absorption: galactose > glucose > fructose
Glucose and galactose from the intestine into endothelial
cells are absorbed by secondary active transport
Carrier protein is specific for D-glucose or Dgalactose.
L-forms are not transported.
There are competition between glucose and
galactose for the same carrier molecule;
thus glucose can inhibit absorption of
Fructose is absorbed from intestine into
intestinal cells by facilitated diffusion.
Absorption of glucose from intestinal cells
into bloodstream is by facilitated diffusion.
Transport of glucose from blood into cells of different
organs is mainly by facilitated diffusion.
The protein facilitating the glucose transport is called
glucose transporter (GluT).
GluT are of 5 types.
GluT1 is seen in erythrocytes and endothelial cells;
GluT2 is located mainly in hepatocytes membranes (it
transport glucose into cells when blood sugar is high);
GluT3 is located in neuronal cells (has higher affinity to
GluT4 - in muscles and fat cells.
GluT5 – in intestine and kidneys;
The fate of glucose molecule in the cell
activated in well
fed, resting state
if glucose is
the NADPH for lipid
pentoses for nucleic
is activated if
energy is required
Regulation of Glycolysis
The rate glycolysis is regulated to meet two major cellular needs:
(1) the production of ATP, and
(2) the provision of building blocks for synthetic reactions.
There are three control sites in glycolysis - the reactions catalyzed by
phosphofructokinase 1, and
These reactions are irreversible.
Their activities are regulated
by the reversible binding of allosteric effectors
by covalent modification
by the regulation of transcription (change of the enzymes amounts).
The time required for allosteric control, regulation by phosphorylation, and
transcriptional control is typically in milliseconds, seconds, and hours, respectively.
1) PFK-1 is
inhibited by ATP
2) Pyruvate kinase
is inhibited by ATP
3) Hexokinase is
inhibited by excess
1) AMP and fructose 2,6bisphosphate (F2,6BP) relieve the
inhibition of PFK-1 by ATP
stimulate the activity of pyruvate
Gluconeogenesis - synthesis of "new" glucose from such
precursors as pyruvate, lactate, certain amino acids, and
intermediates of the tricarboxylic acid cycle.
Most of the reaction steps in the pathway from pyruvate to
glucose 6-phosphate are catalyzed by enzymes of the
glycolytic sequence and thus proceed by reversal of
steps employed in glycolysis. However, there are two
irreversible steps in the normal "downhill" glycolytic
pathway which cannot be utilized in the "uphill"
conversion of pyruvate to glucose 6-phosphate. In the
biosynthetic direction these steps are bypassed by
The first of these bypass steps is the phosphorylation of pyruvate to
phosphoenolpyruvate. The first step is catalyzed by pyruvate
carboxylase of mitochondria:
pyruvate + CO2 + ATP → oxaloacetate + ADP + P
The oxaloacetate formed in this mitochondrial reaction is then
reduced to malate at the expense of NADH by the mitochondrial
form of malate dehydrogenase:
oxaloacetate + NADH + H+ → malate + NAD+
The malate so formed may then leave the mitochondria and in the
cytosol the malate is then reoxidized by the cytoplasmic form of
NAD-linked malate dehydrogenase to form extramitochondrial
malate + NAD+ → oxaloacetate + NADH + H+
In the last step of the bypass, oxaloacetate is acted upon by
phosphoenolpyruvate carboxykinase (GTP) to yield phosphoenolpyruvate
and CO2, a reaction in which GTP serves as the phosphate donor:
oxaloacetate + GTP → phosphoenolpyruvate + CO2 + GDP.
The second crucial point in gluconeogenesis in which a reaction of the
downhill glycolytic sequence is bypassed is conversion of fructose 1,6diphosphate into fructose 6-phosphate:
fructose 1,6-diphosphate + H2O → fructose 6-phosphate + P.
This reaction is catalized by the enzyme fructose diphosphatase.
In some animal tissues, particularly the liver, kidney, and
intestinal epithelium, glucose 6-phosphate may be
dephosphorylated to form free glucose; the liver is the
major site of formation of blood glucose. The hydrolytic
cleavage of glucose 6-phosphate does not occur by
reversal of the hexokinase reaction but is brought about
glucose 6-phosphate + H2O → glucose + P
Glucose-6-phosphatase is not present in muscles or in the
brain, which thus cannot donate free glucose to the blood.
Diabetes mellitus is a disorder in which blood
sugar (glucose) levels are abnormally high because
the body does not produce enough insulin.Insulin a
hormone released from the pancreas, controls the
amount of sugar in the blood.The levels of sugar in
the blood vary normally throughout the day. They
rise after a meal and return to normal within about 2
hours after eating. Once the levels of sugar in the
blood return to normal
often use the full name diabetes
mellitus, rather than diabetes alone, to
distinguish this disorder from diabetes
insipidus, a relatively rare disease that does
not affect blood sugar.
Types of Diabetes mellitus
1: In type 1 diabetes ( insulindependent diabetes or juvenile-onset
diabetes), more than 90% of the insulinproducing cells of the pancreas are
permanently destroyed. The pancreas,
therefore, produces little or no insulin
Only about 10% of all people with diabetes
have type 1 disease. Most people who have
type 1 diabetes develop the disease before
2: In type 2 diabetes ( non-insulindependent diabetes or adult-onset diabetes),
the pancreas continues to produce insulin,
sometimes even at higher-than-normal
levels. However, the body develops
resistance to the effects of insulin, so there is
not enough insulin
to meet the body's needs.
Type 2 diabetes may occur in children and
adolescents, but usually begins in people older than
30 and becomes progressively more common with
age. About 15% of people older than 70 have type 2
diabetes. Obesity is the chief risk factor for
developing type 2 diabetes, and 80 to 90% of
people with this disease are obese. Because obesity
causes insulin resistance, obese people need very
large amounts of insulin
to maintain normal blood sugar levels.
The two types of diabetes have very similar symptoms. The first
symptoms are related to the direct effects of high blood sugar
levels (hyperglycemia). When the blood sugar level rises above
160 to 180 mg/dL, sugar spills into the urine (glucoseuria).
When the level of sugar in the urine rises even higher, the
kidneys excrete additional water to dilute the large amount of
sugar. Because the kidneys produce excessive urine, a person
with diabetes urinates large volumes frequently (polyuria). The
excessive urination creates abnormal thirst (polydipsia).
Because excessive calories are lost in the urine, the person
loses weight. To compensate, the person often feels excessively
hungry. Other symptoms include blurred vision, drowsiness,
nausea, and decreased endurance during exercise.