U N ~ OF JORDAN

Faculty OF Medicine
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LECTURE NO: i 1
,¢'---I DATE: \ 1. I" I 'LOa &
BY THE NAME OF ALLAH
Mttabolis"li.
Some metabolic factors & objective:
I-How we could utilize glucose to get energy.
2-Ruw we could make glucose from Doncarbohydrate
substances.
3-00 Wei-Fed state glucose stored in the form of glycogen.
we can degrade glycogen to get glucose.
S·Wc must know bow to make gluconic acid (an important
compound for dr-ug metabolism).
6-We can prepare one type of sugar from other type
(intercoDversion) that's because there is no essential sugar.
We arc going to talk on these pathways which is vcry
important for the production ofNADPH (electron carrier for
reductive biosynthesis. involve in reactive oxygen species).
Glucose is the primary source of energy for the Nervous
system & for RBC. In aerobic conditions, glucose converts into
Pyruvate but under anaerobic conditions it COD\'erts into Lactate.
-In our bodies, we got about 40 to 50% of energy from
carbohydrate
35% of energy from fat
15% of energy from protein
-60% of carbohydrates are preferable to be complex starch
(bread, ...etc), the remaining carbohydrate are come from
sucrose (table sugar), Disaccharide. monosaccharide, Bnd from
animals glycogen as weD as lactose (from milk).
Some compounds and the Jinks between:
Amylopectin 1-6
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Glycogen 1-6
Fructose a 1-2
Lactose p 1-4
Cellulose p 1-4 (we caD't digest this I)

I.Digestion of carbohydrate start at the mouth where we
have Alpha-Amylase enzyme which acts 00 thee starch and glycogen.
The end product of this process is (maltose, isomaltose (1-6 linkage)
and dextrin (short branch oligosaccharide).
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2-AftCf that when its reach the stomach Alpha-Amylase stop
working and become inactive because urtbe law PH urtbe stomach.
But when it reaches the duodenum it becomes active again and the
higb acidity uftbe stomach is neutralized by the bicarbonate secreted
from the pancreas. And a pancreatic Alpha-Amylase continues the
digestion of starch.
3-then between duodenum and the upper jejunum starch is
almost digested and ready to be absorbed by the small intestine.
The end products are (maltose, isomaltose, sucrose and
lactose (both from the beginning).
7 Amylase endoglycosidase doesn't work on maltose because
it's a terminal sugar and this enzyme (endoglycosidase) work 00 the
middle only.
7Mucosal cell: group of digestive enzyme disaccharide
(isomaltase, maltase, lactase and sucrase).
These enzymes degrade disaccharides to (glucose, fructose
and galactose) which arc absorbed by 2 mechanisms: I-Na
dependent transport system.
2 ~ N a independent transport system.
These sugars go to circulation and distributed to the other
tissues where we bave different form of protein that is uptake of
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these sugars. The absorbion viable is Na independent transport
system (facilitated diffusion).
This is a piece of starch has 1000000 suger residues will be
degraded by Alpha-Amylase to give us maltose, isomaltose and lipid
dextrin which will be degraded and the whole end product will be
(maltose, isomaltose, sucrose and lactose).
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Abnormal deerradation of disaccharide:
Sometime we have a deficiency in disaccharide enzymes.
This deficiency can be genetic, or
due to a variety of intestinal disease or due to a malnutrition
which affect tbe production of these enzymes.
Now we will talk about a genetic. Lactase is the most, the
highcst in descent of deficiency than any other enzyme.
In to 2/3 of the world populations have a deficiency of
enzyme lactase during adulthood. 90% of African people and people
of south cast Asia have lactase deficiency during adulthood. This
deficiency represent a quantity, not that the enzyme they have is
abnormal, but the deficiency on tbe enzyme itself.
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The mechanism by which this age dependent loss of the
enzyme occun is not clear. People who have lactase deficiency they
were have the enzyme but they loss it upon growth.
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Other enzyme genetic is sucrase. This enzyme deficiency can
be found on Greenland Eskimos. In North America, they have 2% of
deficiency as heterozygous.
When these disaccharides are not digested what will
happen?
They reach the Inge intestine with their small molecules
cause increasing on osmotic pressure and that leads to Osmotic
Diarrhea, because they haven't been uptaked. Alter the increasing in
osmotic pressure, the intestinal nora will work on these disaccharide
and it will metabolize them. After this process bacteria will act on
these disaccharide by fermentation and convert tbem to:
2C metabolize, 3C metabolize, C02 and 82 gas.
~ B y measuring the 82 gas, we can know ifthe patient has a
deficiency of an enzyme. We measure the H2 gas by giving the
patient a glass of drink that has aoy of these disaccharides and
measure the H2 in his breath. Then we can diagnose if he has a
deficiency in disaccharidase from these disaccharide.
In addition to diarrhea, tbe increasing of C02 and H2(gas)
will cau.se abdominal cramp.
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to givc you an idea, if you give someone 9g of lactose
which present in 1 glass of milk, this will cause a loss of fluid about 1
liter.
MODosaccbaridcl':
They are absorbed by two mecbanisms; the major t is
Sodium Monosaccharide Co-transport System.
Na is being taken up and fired down from the lumen to the
intracellular space against its concentration.
The movement ofNa is coupled with glucose transport. After
that, the Na is pumped out by NA K ATPASE pump which requires
energy this is what we call secondary active transport.
This process takes place in the intestinal mucosal cells as well
as in the kidney (epithelial cells of renal tubules for reabsorbtion of
the filtered glucose).
is transported against its concentration.
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The uptake of glucose from blood of the intestinal mucosal
cells and its distribution to the other tissue where we have a variety
of transport systems that are Na Independent are carried out by
facilitated diffusion.
We have different transport proteins with different
properties, affinities and maximum capacity. They all depend on the
transporter's location.
~ T h e s e transporters which we abbreviated as Glut
transporter (glut from glucose) arc 14 in nunber. We are going to
talk about the prominent ones:
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I-Glut I: present in RBes & brain. It has low Km and high
affinity for glucose. Even when you have a fasting level ofsuger, it
can still take up glucose.
2-Glut 2: found in liver, kidney and in pancreatic beta cells.
This tnmsporter has a high capacity, high V max but low affinity
(high Km) it has 2 functions:
A-If the suger level increases in blood, it wiu take it and
store it in the previous location.
B-If the suger level decreases in blood, it will release it
from one of the stored previous location.
3-Glut 3: its the glucose transporter in the Neurons. It has
lowKm.
4-Glut 4: found in fat, adipose tissue, skeletal and heart
muscle. It is Insulin dependent. For that reason, Diabetic patient<il
will have problem if they have insulin deficiency. Thais because the
fat cant take suger and convert it to glycerol and fatty acids and
store it. Also, the muscles can't utilize the suger to get energy.
5·Glut 5: is concerned mainly of absorption of fructose. This
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is found on small intestines & testes they absorb fructose. (Also the
sperms prefer fructose as a source of energy).
6-Glut 7: you can find this transporter on the tissues that are
involved in glucose formation in tbe liver and the kidney. They arc
located on the endoplasmic membrane. During the process of
forming glucose, glucose 6 phosphate enter the lumen then it goes out
free.
Catabolism:
In the GI tract, carbohydrates, fats & proteins are degraded
into their monomers. These monomers are absorbed and
metabolized to smaDer constituents producing energy. We have 20
amino acids, differeDt fatty acids aDd different sugars. When
catabolized, they give us few end products (C02, H2 aDd NH3).
Catabolism is a conversion process.
The purposes from catabolism are: I-produce energy
2-produce molecules that
are necessary to build an intcrmediate compound such as acetyl CoA
Anabolism:
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We use precursor molccules (amino acids, fatty acid,
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nitrogen base and somctimes intermediate compound such as acetyl
co enzyme A).
Sometimes we use reducing electron carriers. We can build
a limitless numbcr of protcin!il, carbohydrates, fat and nucleic acids.
So it's a diversion process and requires cncrgy.
In metabolism pathways, we have regulation which bas
different aspects:
- intracellular signals: it inhibits (compound forming
process) by its end products or by intermediate product or allosteric.
This happens quickly within the cell
If the cell needs compound x, it will produce it, and when the
amount of x becomes more than the cell needs, tbe process will be
inhibited by intracellular signals.
7CeUs that arc connected by gap junction, the signals that
regulate metabolism pass through these gaps.
Endocrine glands and other cell'i secrete signals, and some of
these signals travel by a duct system to the blood. These signals going
with the circulation and where they find aoy receptor it binds with it
and induce the formation of a secondary messenger (formation of a
compound within the cell that complete the action).
Two systems of secondary messenger are ea &
Phosphatidylioisitol. We will talk about them in the next lecture.
Other system of the seconda')' messenger is Adenylyl
cyclase.
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-7Any reeeptor looks like a domain, which binds a signal
hormone or a neurotransmitter and consist'i of 7 transmembrane
helical structures. It also consists of an intercellular domain that
interacts with some other proteins.
Tbe previous second messenger systems have a similar
structure ofthis receptor (the ooe explained above) but differ in
type.
A cell can have receptors for many signals: it can bind many
signals some are excitatory others are inhibitory for some reactions
i.e. hormones or neurotransmitten binding to this domain and
followed by a conformational change which results from interactions
between intercellular domain with protein called G-protein.
This protein binds to GTP or GDP and that's why we call it
G-protein.
G-protein may inhibit or stimulate reactions ego In adenylyl
cyclase G-protein makes stimulation then it is called GS protein. iI
consists of trimeric subunits a,p,y.
when G-protein binds with signal hormone, GOP will receive
a phosphate group and converted into GTP. After that, (I subunit
dissociate. Tbis is a membrane bound protein.
The dissociate a subunit will bind another membrane bound
inactive enzyme. Upon this action, adenylyl cyclase become active.
<AMP:
Hydrolysis or phosphorlysis of ATP will lead to a formation
DreAMY.
cAMPis a 1 phosphat groub binds to carbon # 3 in Ribose
suger. This is called 3prime Sprime cAMP.
This protein have an activity called GTPase, it degrades the
GTP to GOP & phosphate group.
~ G D P protein will be associated with subunits and
inactivate the reaction.
cAMPcontinue the reactioD. Secondery messenger bind with
one kind of protein kinase.
We have several protein kinases in our body. Remember that
when u say protein kinase its an enzyme that pbosphorelates
substrates which are proteins. Protein kinase consist of regulatory
'subunits and catalytic subunitll (when attached to it is inactive)
whcn cAMP bind to regulatory subunits these subunits leave the
catalytic site. When the catalytic subunits r alone they will be active.
Catalytic subunits phosphorelate the binding proteins and
these proteins wbich undergo phosphorelation have different
functions, some are activated others are inhibited and others take
part in ion channels which may excite the channel to transport
substances and other proteins may bind to DNA promoters
increasing tbe e x p n ~ s s i o n of specific genes to make more proteins or
enzymes.
The previous phospborelation processes are reversible by
phosphatase enzyme which work after the dissociation of the signals.
Note: cAMP has a very short life and is degraded by enzyme
called pbospbodiesterase which convert cAMP to 5' AMP ( DOt
secondary messenger) by braking the phosphate ester bond.
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Phosphodiesterase is enhibited by methyhanthync
derivatives such as thiophyline and caffeine.
Special thanks 10 3M©©R ,SHAKER AND NADER who
AJelped me in writing this sheet
Tdedicate this sheet to all my colleagues, with my best
wishes
Hashem Abu Mabfouz
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