Sajiman, S.KM., M.

Gizi
 The major source of energy fuel in the average human diet is
carbohydrate,supplying half or more of the total caloric intake.
Roughly half of dietary carbohydrate is in the form of
polysaccharides such as starches and dextrins, derived largely from
cereal grains and vegetables.
The remaining half is supplied as simple sugars, the most important of
which include sucrose, lactose, and, to a lesser extent, maltose,
glucose, and fructose.
Carbohydrates are composed of the elements carbon, hydrogen, and
oxygen.
The ratio of hydrogen to oxygen is the same as that for water: two
parts of hydrogen to one part of oxygen.
The simplest carbohydrates have the formula C6H12O6.
Classification of carbohydrates.
 Tanaman menyimpan glukosa tidak dalam bnetuk molekul
tunggal tetapi dalam bentuk polysaccharides yang disebut
starch.
Terdapat dua macam starch yaitu amylose and amylopectin
Amylose meupakan rantai lurus molekul glikosa, sedangkan
amylopectin merupakan rantai molekus glukosa dengan banyak
cabang
The more open-branched structure of amylopectin increases its
surface area and thus its exposure to digestive enzymes,
resulting in it being more rapidly digested than amylose, which
in turn results in amylopectin raising blood glucose more quickly
than amylose
 Glikogen adalah polisakarida yang disimpan dalam tubuh
hewan termasuk manusia
Glikogen bukan merupakan sumber karbohirat dalam diet,
karena sangat sedikit kandungan glikogen dalam daging
 Serat makanan merupakan bagian dari struktur tumbuhan
dan terkandung pada semua jenis tumbuhan dari makanan
seperti vegetables, fruits, whole grains, and legumes.
Dietary fibers adalah polysaccharides
Pati juga disebut polysaccharides, dietary fibers berbeda
pada ikatan antara monosaccharides yang tidak dapat
dipecah oleh digestive enzymes dalam tubuh
dietary fibers disebut juga nonstarch polysaccharides
Jenis dietary fibers :
soluble fibers
insoluble fibers
 soluble fibers
form gels (viscous), and are easily digested by bacteria in the colon (fermentable).
Sumber : oats, barley, legumes, and citrus fruits,
soluble fibers sering dikaitkan dengan protektif efek terhadap heart disease dan
diabetes memalui menurunkan kadar kolesterol daran dan kadar glukosa darah
Jenis : Pectin, Gums, Mucilages
insoluble fibers
do not form gels (nonviscous), and are less readily fermented.
Sumber : whole grains (bran) and vegetables,
insoluble fibers promote bowel movements, mencegah constipation, and mencegah
diverticular disease
Jenis :lignins, cellulose, hemicellulose
 Thompson. Janice L,
Melinda M. Manore, Linda
A. Vaughan, 2011 The
science of nutrition2nd ed.
Benjamin Cummings
(ebooks)

Peran fiber dalam membantu menurunkan kadar cholesterol darah

(a) When eating a highfiber diet, fiber binds to the bile that is produced from
cholesterol, resulting in relatively more cholesterol being excreted in the feces.
(b) When a lower-fiber diet is consumed, less fiber (and thus cholesterol) is bound to
bile and excreted in the feces.
Carbohydrate Digestion in the GI Tract

Rolfes. Sharon Rady, Kathryn Pinna, Ellie

Whitney, 2012. Understanding Normal and
Clinical Nutrition, Ninth Edition, Wadsworth,
Cengage Learning (ebooks)
 Thompson. Janice L, Melinda M. Manore, Linda
Digestive Enzymes Produced in the A. Vaughan, 2011 The science of nutrition2nd
Gastrointestinal Tract and Their Actions ed. Benjamin Cummings (ebooks)
Hormones Involved in the Regulation of
Digestion

Thompson. Janice L, Melinda M. Manore, Linda

A. Vaughan, 2011 The science of nutrition2nd
ed. Benjamin Cummings (ebooks)
 Polysaccharides and disaccharides are the most important dietary
carbohydrates nutritionally because free monosaccharides are not
commonly present in the diet in significant quantities.
However, some free glucose and fructose are present in honey,
certain fruits, and the carbohydrates added to processed foods such
as high-fructose corn syrup
Before dietary carbohydrates can be used by the bodys cells they
must first be absorbed from the gastrointestinal (GI) tract into the
bloodstream, a process normally restricted to monosaccharidesthe
form of carbohydrates enterocytes can absorb.
Poly-, tri-, and disaccharides therefore must be hydrolyzed. The
hydrolytic enzymes involved are collectively called glycosidases or,
alternatively, carbohydrases.
 Pencernaan polisakarida dimulai dari mulut
Enzim kunci adalah salivary -amylase, yaitu glycosidase yang
spesifik menghidrolisis ikatan (1-4) glycosidic
Ikatan (1-4) pada cellulose, (1-4) pada lactose, dan ikatan (1-
6) pada rantai cabang amylopectin resistant terhadap -amylase
Pencernaan karbohidrat dalam mulut berlangsung singkat sehingga
hanya sedikit mono-or disaccharides yang dihasilkan.
Didalam lambung salivary amylase masih bekerja menghirolisis
karbohidrat sampai asam lambung penetrates the food bolus dan
rendahnya pH lambungmenyebabkan enzim menjadi inactivate
Pada tahap ini , pati mengalami partially hydrolyzed, dengan
products utama adalah dextrins, (merupakan short-chain
polysaccharides) dan maltose
 The starches move into the duodenum and jejunum,
Further digestion of the dextrins is resumed in the small intestine
by the -amylase of pancreatic origin, which is secreted into the
duodenal contents.
The presence of pancreatic bicarbonate in the duodenum
elevates the pH to a level favorable for enzymatic function.
If the dietary starch form is amylose, which is unbranched, the
products of -amylase hydrolysis are maltose and the
trisaccharide maltotriose, which undergoes slower hydrolysis to
maltose and glucose
Structure of starches
 The hydrolytic action of -amylase on amylopectin, produces
glucose and maltose, as it does with amylose.
However, the 1-6 bonds linking the glucose residues at the
branch points of the molecule cannot be hydrolyzed by -
amylase
Further digestion by -amylase removes glucose units until
isomaltose, a three-unit triose with one unit attached with an
(1-6) glycosidic bond
Isomaltose is hydrolyzed by (1-6)-glycosidase (-dextrinase or
isomaltase), which is located in the brush border and is the only
glycosidase capable of hydrolyzing (1-6) linkages
 Virtually no digestion of disaccharides or small
oligosaccharides occurs in the mouth, stomach, or lumen of the
small intestine.
In the human, digestion takes place entirely in the upper small
intestine.
Unlike -amylase activity, disaccharidase activity occurs in the
microvilli of the intestinal mucosal cells (the brush border), rather
than in the intestinal lumen
Among the enzymes located on the mucosal cells are lactase,
sucrase, maltase, and isomaltase
 Lactase catalyzes the cleavage of lactose to equimolar amounts
of galactose and glucose.
Lactase activity is high in infants.
In most mammals, including humans, the activity of lactase
decreases a few years after weaning.
This diminishing activity can lead to lactose malabsorption and
lactose intolerance.
Sucrase hydrolyzes sucrose to yield one glucose and one
fructose residue.
Maltase hydrolyzes maltose to yield two glucose units.
Isomaltase (also called -dextrinase) hydrolyzes the 1-6 bond
of isomaltose
 Thompson. Janice L, Melinda M. Manore, Linda
A. Vaughan, 2011 The science of nutrition2nd
ed. Benjamin Cummings (ebooks)

The four types of absorption that occur in the small intestine.

(a) In passive diffusion,nutrients pass through the enterocytes and into the bloodstream without
the use of a carrier protein or the requirement of energy.
(b) In facilitated diffusion, nutrients are shuttled across the enterocytes with the help of a carrier
protein without the use of energy.
(c) active transport, energy is used along with a carrier protein to transport nutrients against
their concentration gradient.
(d) In endocytosis, a small amount of the intestinal contents is engulfed by the cell membrane of
the enterocyte and released into the interior of the cell.
 Glucose, is absorbed into the intestinal mucosa cell by several
pathways These include active transport and facilitated
transport
active transport :
The active transport mechanism for glucose and galactose absorption into
enterocytes requires energy as ATP and the involvement of a specific
receptor.
The glucose galactose receptor has been designated sodium-glucose
transporter 1 (SGLT1)
A mutation in the SGLT1 gene is associated with glucose galactose
malabsorption.
The transport protein of SGLT1 has two binding sites: One binds Na+ and
the other binds glucose
Absorption of Monosaccharides

Rolfes. Sharon Rady, Kathryn Pinna, Ellie

Whitney, 2012. Understanding Normal and
Clinical Nutrition, Ninth Edition, Wadsworth,
Cengage Learning (ebooks)
 The glucose binding site is not available unless the transport protein has
already bound a Na+.
The attachment of sodium to the carrier increases the transport proteins
affinity for glucose.
Sodium is moving down a concentration gradient because the intracellular
concentration of Na+ is low.
When Na+ is released inside the cell, the carriers affinity for glucose is
decreased, and the glucose is released into the cell.
Na+/K+-ATPase then pumps the Na ions back out of the cell.
 Facilitated Transport
All glucose absorption is not dependent upon SGLT1.
At times of high glucose concentration in the intestinal mucosa,such as after a
large carbohydrate meal, glucose is transported into the enterocyte by
facilitated transporter type 2 (GLUT2).
GLUT2 also transports glucose, galactose, and fructose out of the enterocyte
and is located at the basolateral membrane.
At times when the glucose concentration of the lumen of the intestine exceeds
the blood concentration, intracellular GLUT2 is translocated to the apical
membrane by the movement of the cytoskeleton and the contraction of myosin
GLUT2 has a high affinity for both glucose and fructose.
After high-carbohydrate meals, more glucose (and fructose) is transported
into the enterocyte by facilitated transport than by active transport using
SGLT1.
 Fructose is transported into the mucosal cell by a specific facilitative
transporter GLUT5
GLUT5 has a high affinity for fructose and is not influenced by the
presence of glucose
This transport is independent of the active, Na+-dependent transport
of glucose (SGLT), but the rate of uptake is much slower than that of
both glucose and galactose.
fructose is absorbed, which slows its entry and produces a smaller
rise in blood glucose
Fructose is transported from the enterocyte into the portal vein by
GLUT2
GLUT2 also transports glucose and galactose out of the enterocyte
and is located at the basolateral membrane
Fructose is transported from the mucosal cell by GLUT2, the same
transporter that moves glucose out of the cell.
 Following transport of glucose, galactose, and fructose across
the wall of the intestine, they enter the portal circulation,where
they are carried directly to the liver.
The liver is the major site of metabolism of galactose and
fructose,
fructose and galactose can be converted to glucose and can be
stored as liver glycogen, returned to the bloodstream to
maintain circulating glucose levels, or catabolized for energy
Transport of monosaccharides into enterocytes.
a. Active transport of glucose and galactose requiring ATP and Na+.
b. Facilitated transport of glucose and galactose into the enterocyte by GLUT 2 when the
intestinal lumen glucose levels are high; glucose and galactose may also exit the cell with
assistance from GLUT 2.
c. Fructose entering the enterocyte via transport facilitated by GLUT 5 and leaving the cell via
transport facilitated by GLUT 2.
 GLUT1
GLUT1 is responsible for the basic supply of glucose to erythrocytes,
endothelial cells of the brain, and most fetal tissue.
GLUT1 supplies the glucose to the developing central nervous system
during embryogenesis.
GLUT2
predominant expression in the -cells of the pancreas, liver, small intestine,
and kidney. As discussed previously,
GLUT2 is involved in the transport of glucose and fructose from
enterocytes into the portal blood, and when the concentration of glucose
in the intestinal lumen is high, it transports glucose and fructose into the
enterocyte.
 GLUT3
Predominant expression in those tissues that are highly dependent upon
glucose, such as the brain and neurons.
GLUT3 also expressed in cells and tissues that have a high requirement for
glucose such as spermatozoa,the placenta, and preimplantation embryos.
Some data suggest that a possible disregulation of GLUT3 might lead to
glucose deficits in the brain and thus to dyslexiain children.
GLUT4
GLUT4 is the primary means by which insulin is responsible for the cellular
uptake of glucose in muscle and adipose tissue.
Other cells and tissues such as the liver, kidney, erythrocytes, and brain do not
express GLUT4 and therefore are not dependent upon insulin for glucose
uptake
GLUT5
specific for the transport of fructose
It is expressed primarily in the small intestine
 The carbohydrate consumed in food is digested and absorbed
and enters the bloodstream causing blood glucose to rise
Blood glucose levels are normally tightly controlled by the liver
and hormones secreted by the pancreas.
If these hormones are not produced normally or if the body
does not respond to them normally, blood glucose levels can
rise too high or drop too low.
Diabetes mellitus is a disease in which blood glucose levels are
consistently above the normal range
hypoglycemia is a condition in which blood glucose levels
drop below the normal range.
 Gula darah puasa adalah alat skrining yang sangat baik untuk diabetes.
Kriteria untuk diagnosis diabetes mellitus, sebagaimana dikembangkan oleh
American Diabetes Association adalah sebagai berikut :
konsentrasi glukosa plasma sewaktu 200 mg / dL (11,1 mmol / L). Sewaktu
didefinisikan sebagai setiap saat sepanjang hari tanpa memperhatikan waktu sejak
makanan terakhir.
Gula darah puasa 126 mg / dL (7.0 mmol / L). Puasa didefinisikan sebagai tidak
ada asupan kalori selama minimal 8 jam.
2 jam postprandial (PP) 200 mg / dL (11,1 mmol / L) selama toleransi glukosa oral
test (OGTT). Tes harus dilakukan seperti yang dijelaskan oleh WHO, menggunakan
beban glukosa yang mengandung setara dengan 75 g glukosa dilarutkan dalam air.
Normal Values
Normal fasting glucose: FPG <100 mg/dL (<5.6 mmol/L SI units)
Impaired fasting glucose: FPG 100125 mg/dL (5.66.9 mmol/L SI units)
Provisional diagnosis of diabetes: FPG 126 mg/dL (7.0 mmol/L SI units)
Regulation of blood glucose : Insulin and glucagon are key factors in controlling blood
glucose. When blood glucose rises above the normal range of 70 to 90 milligrams per
deciliter (mg/dL) 1 , insulin is released 2 to lower it 3 and 4 . Blood glucose then falls
back into the normal range 5 .
When blood glucose falls below the normal range 6 , glucagon is released 7 , which
has the opposite effect of insulin 8 and 9 . This then restores blood glucose to the
normal range 10 . Other hormones, such as epinephrine, norepinephrine, cortisol, and
growth hormone, also contribute to blood glucose regulation
Gordon M. Wardlaw, Anne M. Smith, 2012 .Contemporary Nutrition : a Functional Approach 2nd ed. The
McGraw-Hill Companies
 Blood glucose homeostasis is regulated primarily by two
hormones: insulin and glucagon
When the concentration of glucose in the blood is high, such as
during and immediately after a meal, the pancreas releases the
hormone insulin into the bloodstream
Insulin delivers messages to various body cells to cause the level
of glucose in the blood to fall.
In the liver, insulin promotes the storage of glucose as glycogen and, to a
lesser extent, fat.
In muscle, insulin stimulates the uptake of glucose for energy production
and the synthesis of muscle glycogen for energy storage).
Insulin also stimulates protein synthesis and, in fat-storing cells, it increases
glucose uptake from the blood and stimulates lipid synthesis
Role of Insulin in Cellular Uptake of Glucose Binding of insulin to its receptor causes
insulin-responsive glucose transporters to relocate from the cytoplasm to the cell
membrane, facilitating the movement of glucose molecules across the cell membrane.
Insulin Promotes Energy Storage The pancreas increases its release of the hormone
insulin in response to high blood glucose. Insulin stimulates glucose transport into cells
and promotes energy storage
 when a person has not eaten for a few hours and blood glucose
begins to fall, the pancreas releases the hormone glucagon
Glucagon signals liver cells to break down glycogen into glucose,
which is released into the bloodstream.
Glucagon also stimulates the liver to synthesize new glucose molecules
by gluconeogenesis
Newly synthesized glucose is released into the blood to prevent
blood glucose from dropping below the normal range.
Gluconeogenesis can also be stimulated by the hormone epinephrine,
also known as adrenaline.
This hormone, which is released in response to dangerous or stressful
situations, enables the body to respond to emergencies.
It causes a rapid release of glucose into the blood to supply the
energy needed for action.
Glucagon Promotes Mobilization of Stored Energy The pancreas increases its release
of the hormone glucagon in response to low blood glucose. Glucagon promotes the
breakdown of liver glycogen, fat (adipose tissue), and protein (muscle). Glucagon
also promotes the synthesis of ketones and the production of glucose from
noncarbohydrate sources.
 Food
Insulin
Exercise
Stress
Illness

American Diabetes Association complete guide to diabetes 4th ed. 2005. American
Diabetes Association. United States of America
 Blood glucose rises after a meal depends on many things.
Different foods have different amounts of carbohydrate and will
produce different amounts of glucose.
Carbohydrates come in several forms that take various amounts of
time to be digested and that affect the blood glucose differently.
Fat or protein can slow down digestion and the rate at which glucose
levels rise.
High protein foods can raise blood glucose levels but do so more
slowly than foods containing mostly carbohydrate.
Carbohydrate containing foods that are also high in fat and protein
have a low GI because of the effects of these other components on
gastric emptying.
 Blood glucose rises after a meal
glucose signals the body to release insulin.
When there is too much glucose in the blood, insulin is released.
Insulin reduces the amount of glucose in the blood
Insulin then lets glucose into the cells that need it.
Without insulin, cells in the body cant get the energy they need
to live and grow.
 physically active (PA) its good for your overall health.
PA can help prevent heart disease and other health problems
PA improves blood flow and muscle tone.
PA can even help you handle stress
When exercise, muscles work harder and use up the glucose
they have stored for fuel.
When the glucose stored in muscle runs low, glucose from the
blood is used.
Exercise can help use up some of the glucose that builds up in
the blood.
 Everyone seems stressed out these days
Stress can produce hormones that can shoot blood glucose
levels up and out of desired range
 When youre sick, your body is also stressed.
stress, body releases hormones that help fight the illness.
But these hormones also counteract the effect of insulin in
lowering blood glucose and cause blood glucose levels to go
up.
 The first stage of cellular respiration takes place in the cytosol
of the cell and, meaning glucose breakdown.
Because oxygen isnt needed for this reaction, glycolysis is
sometimes called anaerobic metabolism.
In glycolysis, the 6-carbon sugar glucose is broken into two 3-
carbon molecules called pyruvate
1. Hexokinase (muscle)/Glucokinase (liver) catalyzes:
Phosphorylation of glucose to give glucose-6-phosphate (ATP is
the source of the phosphate group).

Glucose + ATP glucose-6-P + ADP

 6 CH OPO 2
2 3
5 6 CH OPO 2 1CH2OH
H O H 2 3
O
H
4 H 1 5 H HO 2
OH
OH OH H 4 3 OH
3 2
OH H
H OH
Phosphoglucose Isomerase
glucose-6-phosphate fructose-6-phosphate
2. Phosphoglucose Isomerase catalyzes:
Isomerization of glucose-6-phosphate to give fructose-6-
phosphate.
glucose-6-P (aldose) fructose-6-P (ketose)
 Phosphofructokinase
6 CH OPO 2 1CH2OH 6 CH OPO 2 1CH2OPO32
2 3 2 3
O ATP ADP O
5 H HO 2 5 H HO 2

H 4 3 OH Mg2+ H 4 3 OH
OH H OH H
fructose-6-phosphate fructose-1,6-bisphosphate
3. Phosphofructokinase catalyzes:
Phosphorylation of fructose-6-phosphate to give fructose-
1,6-bisphosphate (ATP is the source of the phosphate
group).
fructose-6-P + ATP fructose-1,6-bisP + ADP
 2
1CH2OPO3

2C O
H O
2
HO 3C H Aldolase 3
CH2 OPO 3 1C

H 4C OH 2C O + H 2C OH
2
H C OH 1CH2OH 3 CH2OPO3
5
2
6 CH2 OPO 3 dihydroxyacetone glyceraldehyde-3-
phosphate phosphate
fructose-1,6-
bisphosphate
Triosephosphate Isomerase

4. Aldolase catalyzes:
Cleavage of fructose-1,6-bisphosphate to give two 3-carbon
fragments, glyceraldehyde-3-phosphate and dihydroxyacetone
phosphate

fructose-1,6-bisphosphate dihydroxyacetone-P + glyceraldehyde-3-P

 2
1CH2OPO3

2C O
H O
2
HO 3C H Aldolase 3
CH2 OPO 3 1C

H 4C OH 2C O + H 2C OH
2
H C OH 1CH2OH 3 CH2OPO3
5
2
6 CH2 OPO 3 dihydroxyacetone glyceraldehyde-3-
phosphate phosphate
fructose-1,6-
bisphosphate
Triosephosphate Isomerase

5. Triose Phosphate Isomerase (TIM) catalyzes:

Isomerization of dihydroxyacetone phosphate to give glyceraldehyde-3-
phosphate.
dihydroxyacetone-P glyceraldehyde-3-P
 Glyceraldehyde-3-phosphate
Dehydrogenase
H O + H+ O OPO32
1C NAD+ NADH 1C
+ Pi
H C OH H C OH
2 2
2 2
3 CH2OPO3 3 CH2OPO3

glyceraldehyde- 1,3-bisphospho-
3-phosphate glycerate

6. Glyceraldehyde-3-phosphate Dehydrogenase
catalyzes:
Oxidation (and phosphorylation) of glyceraldehyde-3-
phosphate to give 1,3-bisphosphoglycerate.
glyceraldehyde-3-P + NAD+ + Pi
1,3-bisphosphoglycerate + NADH + H+
 Phosphoglycerate Kinase
O OPO32 ADP ATP O O
1C 1
C
H 2C OH H 2C OH
2 Mg2+ 2
3 CH2 OPO 3 3 CH2 OPO 3

1,3-bisphospho- 3-phosphoglycerate
glycerate

7. Phosphoglycerate Kinase catalyzes:

Transfer of a phosphate group from 1,3 bisphosphoglycerate to
ADP (phosphorylation of ADP to ATP) to give 3-
phosphoglycerate

1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
 Phosphoglycerate Mutase
O O O O
C
1
C
1
H 2C OH H 2C OPO32
2
3 CH2OPO3 3 CH2OH
3-phosphoglycerate 2-phosphoglycerate

8. Phosphoglycerate Mutase catalyzes:

Isomerization of 3-phosphoglycerate to give 2-phosphoglycerate
3-phosphoglycerate 2-phosphoglycerate
 Enolase
O H O OH O
O O O
C C 1
C
1
H 2 C OPO32 C OPO32 2C OPO32

3 CH2OH CH2OH 3 CH2

2-phosphoglycerate enolate intermediate phosphoenolpyruvate

9. Enolase catalyzes:
Dehydration of 2-phosphoglycerate to give
phosphoenolpyruvate.
2-phosphoglycerate phosphoenolpyruvate + H2O
 Pyruvate Kinase
O O O O
ADP ATP
1
C 1
C

2
C OPO32 2
C O

3 CH2 3 CH3
phosphoenolpyruvate pyruvate

10. Pyruvate Kinase catalyzes:

Transfer of a phosphate group from phosphoenolpyruvate to
ADP (phosphorylation of ADP to ATP) to give pyruvate
phosphoenolpyruvate + ADP pyruvate + ATP
 Hexokinase

Phosphoglucose Isomerase

Phosphofructokinase

Aldolase

Triose Phosphate Isomerase

Glyceraldehyde-3-phosphate Dehydrogenase

Phosphoglycerate Kinase

Phosphoglycerate Mutase

Enolase

Pyruvate Kinase
 citrate synthase

malate aconitase
dehydrogenase

fumarase

isocitrate
dehydrogenase

succinyl-CoA
synthetase
 In liver The synthesis and breakdown of glycogen is regulated
to maintain blood glucose levels.

In muscle - The synthesis and breakdown of glycogen is

regulated to meet the energy requirements of the muscle cell.
 the liver is a major site of glycogen synthesis and storage.
Glycogen accounts for as much as 7% of the weight of the liver.
Liver glycogen can be broken down to glucose and reenter the bloodstream.
Therefore, it plays an important role in maintaining glucose homeostasis.
The other major site of glycogen storage is skeletal muscle.
In human skeletal muscle, glycogen generally accounts for a little less than
1% of the weight of the tissue.
Although the concentration of glycogen in the liver is greater, muscle stores
account for most of the bodys glycogen (75%) because the muscle makes
up a much greater portion of the bodys weight than the liver does.
The glycogen stores in muscle are an energy source within that muscle fiber
and cannot directly contribute to blood glucose levels. (Muscle lacks the
enzyme that converts the phosphorylated glucose back to free glucose.)
 Glucose is first phosphorylated upon entering the cell, producing glucose-6-
phosphate.
In muscle cells, the enzyme catalyzing this phosphate transfer from ATP is
hexokinase
Glucose phosphorylation in the liver is catalyzed primarily by a called
glucokinase
The phosphate is transferred from the 6-carbon of the glucose to the 1-carbon in a
reaction catalyzed by the enzyme phosphoglucomutase.
 Energy derived from the hydrolysis of the --phosphate anhydride bond of uridine
triphosphate (UTP to UMP) allows the resulting uridine monophosphate to be coupled to the
glucose-1-phosphate to form uridine diphosphate glucose (UDP-glucose).
Glucose is incorporated into glycogen as UDP-glucose.
 The breakdown of glycogen into individual glucose units
glycogenolysis is regulated by hormones, most importantly
glucagon (of pancreatic origin) and the catecholamine hormone
epinephrine (produced in the adrenal medulla).
Glucagon and epinephrine function antagonistically to insulin in
regulating the balance between free (glucose) and stored
glucose (glycogen)
Muscle is responsive to epinephrine.
Liver is responsive to glucagon and somewhat responsive to
epinephrine.
 In the liver, phosphoglucomutase converts glucose-1-phosphate
to glucose-6- phosphate, which is then hydrolyzed by glucose-6-
phosphatase to release free glucose
glucose leaves the cell and enters the bloodstream.
Only gluconeogenic tissues such as the liver can make glucose
available to the body at large.
Other tissues that store glycogen, such as muscle, lack glucose-
6-phosphatase and so break down glycogen only for their own
needs.
In these tissues, the glucose-1-phosphate liberated by
phosphorolysis of glycogen is converted to glucose-6-
phosphate, which then enters glycolysis
 Liver contains glucose 6-phosphatase.
Muscle does not have this enzyme.
WHY?
The liver releases glucose to the blood to be taken up by brain and
active muscle. The liver regulates blood glucose levels.

The muscle retains glucose 6-phosphate to be use for energy.

Phosphorylated glucose is not transported out of muscle cells.
 All cells are dependent on glucose.
Glucose level in blood plasma must be stable.
Brain is especially sensitive to the decrease of glucose level (the
daily glucose requirement of the brain in a typical adult human being
is about 120 g).
160 g of glucose needed daily by the whole body
Red blood cells use only glucose as a fuel.
The amount of glucose present in body fluids is about 20 g, and that
readily available from glycogen is approximately 190 g.
During period of fasting glycogen in liver is mobilized but it only lasts
12 to 24 hours and this source of glucose may not fulfill metabolic
need.
During a longer period of starvation organism must synthesize
glucose from smaller noncarbohydrate precursor molecules.
 Gluconeogenesis synthesis of glucose from
noncarbohydrate precursors

Liver and kidney are major sites of glucose synthesis

precursors: lactate, pyruvate, glycerol and some amino acids (glucogenic
amino acids ; especially glycine, alanine, glutamate, and aspartate)
Under fasting conditions, gluconeogenesis supplies almost all of the
bodys glucose
Gluconeogenesis universal pathway. It present in animals,
microorganisms, plants and fungi
Plants synthesize glucose from CO2 using the energy of sun,
microorganisms from acetate and propionate
 In glycolysis, glucose is converted into pyruvate; in
gluconeogenesis, pyruvate is converted into glucose.
However, gluconeogenesis is not a reversal of glycolysis.
There are three irreversible reactions in glycolysis catalyzed by
hexokinase, phosphofructokinase, and pyruvate kinase.

1. Glucose + ATP glucose-6-phosphate + ADP (hexokinase) G = -8 kcal

mol-1
3. Fructose-6-phosphate + ATP fructose-1,6-biphosphate + ADP
(phosphofructokinase) G = -5.3 kcal mol-1
10. Phosphoenolpyruvate + ADP pyruvate + ATP (pyruvate kinase) G = -4
kcal mol-1

These three reactions must be bypassed in gluconeogenesis

 gluconeogenesis
glycolysis
CHARLOTTE W. PRATT., KATHLEEN CORNELY
2014 Essential Biochemistry Third Edition. John
Wiley and Sons
 Bypassed Reactions in Gluconeogenesis

Phosphoenolpyruvate is formed from pyruvate by way of

oxaloacetate through the action of pyruvate carboxylase and
phosphoenolpyruvate carboxykinase.

Pyruvate + CO2 + ATP + H2O oxaloacetate + ADP + Pi + 2H+

Oxaloacetate + GTP phosphoenolpyruvate + GDP + CO2

Fructose 6-phosphate is formed from fructose 1,6-bisphosphate.

Enzyme - fructose 1,6-bisphosphatase.

Fructose 1,6-bisphosphate + H2O fructose 6-phosphate + Pi

Glucose is formed by hydrolysis of glucose 6-phosphate in a

reaction catalyzed by glucose 6-phosphatase.

Glucose 6-phosphate + H2O glucose + Pi

 Pyruvate cannot be converted directly back to
phosphoenolpyruvate because pyruvate kinase catalyzes an
irreversible reaction
The first step in gluconeogenesis is the carboxylation of
pyruvate to form oxaloacetate at the expense of a molecule of
ATP
Enzyme pyruvate carboxylase is present only in mitochondria.
Pyruvate is transported into mitochondria from cytoplasm; the
part of pyruvate is formed in mitochondria from amino acids.
Essential cofactor of pyruvate carboxylase is biotin, which
serves as a carrier of CO2.
Oxaloacetate is polar molecule and can
not pass through the mitochondria
membrane into cytoplasm

Therefore it is reduced:
oxaloacetate + NADH2 malate + NAD+
Enzyme malate dehydrogenase

Malate passes through the mitochondria

membrane into cytoplasm and again oxidized
to oxaloacetate (enzyme malate
dehydrogenase):
malate + NAD+ oxaloacetate + NADH2

Cytoplasmic oxaloacetate is
decarboxylated to phosphoenolpyruvate
by phosphoenolpyruvate carboxykinase
Pyruvate carboxylase is allosterically activated by acetyl CoA.

Accumulation of acetyl CoA from fatty acid oxidation signals abundant

energy, and directs pyruvate to oxaloacetate for gluconeogenesis.

Pyruvate carboxylase reaction

biotin

This reaction takes place in mitochondria matrix.

 Phosphoenolpyruvate carboxykinase reaction

Reaction takes place in the cytosol.

In decarboxylation reaction GTP donates a phosphoryl group.
Oxaloacetate is simultaneously decarboxylated and
phosphorylated by phosphoenolpyruvate carboxykinase.
One molecule of ATP and one molecule of GTP were spent to
lift pyruvate to the energy level of phosphoenlpyruvate.
 A metabolically irreversible reaction
The enzyme responsible for this step is fructose 1,6-
bisphosphatase
F1,6BPase is allosterically inhibited by AMP and fructose
2,6-bisphosphate (F2,6BP)
 In most tissues, gluconeogenesis ends with the formation
of glucose 6-phosphate (G-6P).

Glucose 6-phosphate, unlike free glucose, cannot diffuse

out of the cell.

The generation of free glucose is controlled in two ways:

enzyme responsible for the conversion of glucose 6-phos-phate
into glucose, glucose 6-phosphatase, is regulated;
enzyme is present only in tissues whose metabolic duty is to
maintain blood-glucose homeostasis liver and to a lesser extent
kidney, pancreas, small intestine.
 Michelle McGuire and Kathy A. Beerman. 2011.Nutritional Sciences: From
Fundamentals to Food, Second Edition. Wadsworth Cengage Learning

The Cori Cycle : The Cori cycle is a metabolic pathway that involves both glycolysis
and gluconeogenesis. Under conditions of limited oxygen availability, muscles
break down glucose to lactate via glycolysis. Lactate is released into the blood and is
converted by the liver to glucose via gluconeogenesis.
Sajiman, S.KM., M. Gizi
 PPP : Pentosa
Phospat Pathway Fungsi utama :

Produksi NADPH untuk

Jalur alternatif sintesis reduktif
untuk metabolisme seperti biosintesis
glukosa asam lemak serta
steroid

Produksi residu ribosa

Tidak menghasilkan untuk biosintesis
ATP nukleotida serta asam
nukleat
 The Pentose Phosphate Pathway (also called Phosphogluconate
Pathway, or Hexose Monophosphate Shunt)
The primary results of the pathway are:
NADPH, used in reductive biosynthesis reactions within cells (e.g. fatty acid
synthesis).
Production of ribose-5-phosphate (R5P), used in the synthesis of
nucleotides and nucleic acids.
Production of erythrose-4-phosphate (E4P), used in the synthesis of
aromatic amino acids.
 Function : Production of
For NADPH
Ribose 5P
Site :
In the cytoplasm of all cells except muscle,
and nonlactating mammary gland (low
activity)
 Generation of NADPH
mainly used for reductive syntheses of fatty acids, steroids,
amino acids via glutamate dehydrogenase; and production
of reduced glutathione in erythrocytes and other cells.
active in liver, adipose tissue, adrenal cortex, thyroid,
erythrocytes, testes, and lactating mammary gland
not active in non-lactating mammary gland and has low
activity in skeletal muscle.
Production of ribose residues for nucleotide and
nucleic acid synthesis.
 the activity of the pentose phosphate pathway is high in rapidly
dividing cells that must synthesize large amounts of DNA.
the pentose phosphate pathway not only produces ribose, it
also provides a reducing agent (NADPH) required for the
reduction of ribose to deoxyribose.
 Oxidative phase
In this phase, two molecules of NADP+ are reduced to NADPH, utilizing the
energy from the conversion of glucose-6-phosphate into ribulose 5-
phosphate.
Non-oxidative phase
 The starting point of the pentose phosphate pathway is glucose-
6-phosphate,
glucose-6-phosphate can be derived from
free glucose,
glucose-1-phosphate produced by glycogen phosphorolysis,
gluconeogenesis
Reactants Products Enzyme Description
Dehydrogenation. The
hydroxyl on carbon 1 of
glucose 6-phosphate
Glucose 6-phosphate + 6-phosphoglucono-- glucose 6-phosphate
turns into a carbonyl,
NADP+ lactone + NADPH dehydrogenase
generating a lactone,
and, in the process,
NADPH is generated.
6-
6-phosphoglucono-- 6-phosphogluconate
phosphogluconolactonas Hydrolysis
lactone + H2O + H+
e
Oxidative
decarboxylation. NADP+
is the electron acceptor,
6-phosphogluconate + ribulose 5-phosphate 6-phosphogluconate
generating another
NADP+ + NADPH + CO2 dehydrogenase
molecule of NADPH, a
CO2, and ribulose 5-
phosphate.
 Glucose-6-phosphate dehydrogenase catalyzes the metabolically
irreversible transfer of a hydride ion from glucose-6-phosphate
to NADP1, forming a lactone and NADPH:
 deficiency of glucose-6-phosphate dehydrogenase :
decreases the cellular production of NADPH, interferes with
the normal function of certain oxidationreduction processes
The cells more susceptible to oxidative damage
Detoxification of H2O2 is inhibited, and cellular damage results - lipid
peroxidation leads to erythrocyte membrane breakdown and
hemolytic anemia
individuals with glucose-6-phosphate dehydrogenase
deficiency are also more resistant to malaria
The lactone intermediate is hydrolyzed to 6-phosphogluconate by
the action of 6-phosphogluconolactonase
6-phosphogluconate is oxidatively decarboxylated in a reaction that
converts the six-carbon sugar to a five-carbon sugar and reduces a
second NADP1 to NADPH

The two molecules of NADPH produced for each glucose molecule that enters the
pathway are used primarily for biosynthetic reactions, such as fatty acid synthesis
and the synthesis of deoxynucleotides.
The ribulose-5-phosphate product of the oxidative phase of the
pentose phosphate pathway can isomerize to ribose-5-
phosphate

Ribose-5-phosphate is the precursor of the ribose unit of

nucleotides.
Reactants Products Enzymes

ribulose 5-phosphate ribose 5-phosphate Ribulose 5-Phosphate Isomerase

Ribulose 5-Phosphate 3-
ribulose 5-phosphate xylulose 5-phosphate
Epimerase

xylulose 5-phosphate + ribose 5- glyceraldehyde 3-phosphate

transketolase
phosphate + sedoheptulose 7-phosphate

sedoheptulose 7-phosphate + erythrose 4-phosphate +

transaldolase
glyceraldehyde 3-phosphate fructose 6-phosphate

xylulose 5-phosphate + erythrose glyceraldehyde 3-phosphate

transketolase
4-phosphate + fructose 6-phosphate
 Ellie Whitney, Sharon Rady Rolfes 2013. Understanding Nutrition, Thirteenth
Edition. Wadsworth, Cengage Learning
Sareen S. Gropper, Jack L. Smith. 2013 Advanced Nutrition and Human
Metabolism, Sixth Edition. Wadsworth, Cengage Learning
Janice L. Thompson, Melinda M. Manore, Linda A. Vaughan. 2011. The
science of nutrition 2nd ed. Pearson Education, Inc., publishing as Pearson
Benjamin Cummings
Charlote W. Pratt, Kathleen Cornely, 2014. Essential Biochemistry. John
Wiley and Sons
American Diabetes Association complete guide to diabetes 4th ed. 2005.
ADA. United States of America