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Transcript
Lec:3
biochemistry
Dr. Anwar j almzaiel
Digestion and absorption
The gastrointestinal tract (G.I.T)
The principle function of the gastrointestinal tract and its associated organs is
the digestion and absorption of nutrient. The major foods are ingested as
macromolecules (carbohydrate, proteins, lipids and nucleic acids), which must
be broken down to small components for absorption. This is achieved by
enzymes hydrolases secreted by the G.I.T, together with the mechanical process
involve in digestion. The digestive sequence is controlled by neural and
hormonal factors and the gut is an active endocrine organ.
Protein
Starch
triglycerides
amino acid
monosaccharides
monoacylglycerol, glycerol and fatty acid
Digestion: A process of converting complicated compounds
from the insoluble, non-diffusible state into simple products of
higher solubility and great diffusiblity making easier absorption
for utilization by tissue
The important digestive secretion are (daily)
secretion
Vol (ml)
pH
Salivary secretion
1000
6.8
Gastric juice
1500
1-3.5
Pancreatic juice
1000
8-8.3
Bile juice
1000
7.8
Intestinal juice
1800
7.5-8
Metabolism:
Is the network of chemical reactions that occur inside the body
(within the cell). It describes all biochemical reactions occurring in
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the cell exchanging matter and energy between the cell and its
environment.
Metabolites are the small molecules that are intermediates in the
degradation or biosynthesis of biopolymers. The term intermediary
metabolism is applied to the reactions involving these low-molecularweight molecules.
Metabolic pathways fall into three categories:
1. Anabolic pathways which are those involved in the synthesis of
large and more complex compounds from small molecules for
example synthesis of protein from amino acids, synthesis of
glycogen from carbohydrates and nucleic acid. Free energy is
required for these processes.
2. Catabolic pathways which are involved in the breakdown of
large molecules into small molecules, therefore, it is the process
of degradation (it can be absorbed and metabolized) for example
the respiratory chain and oxidative phosphorylation).
3. Amphibolic pathways which occur at the crossroad of
metabolism, acting as links between the anabolic and catabolic
pathways
After digestion, the simple food materials pass into the cells by a
process called “absorption”. So the first part of metabolism is the
digestion & absorption.
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Mouth
Ingestion: In the mouth food is ground, moistened and lubricated by saliva a
mucal fluid (secreted by three pairs of salivary glands; parotid, submaxillary,
and sublingual glands). It is colourless, opalescent, slimy fluid secreted at a
rate of 1500 cc/day, this depends on the type and amount of food.
Digestion: salivary glands secrete α-amylase, which digests starch into small
segments of α-dextrins, maltose and into individual soluble sugars. Salivary
glands also secrete lysozyme, which kills bacteria but is not classified as a
digestive enzyme.
Then the resulting bolus of food is swallowed into the esophagus and carried by
peristalsis to the stomach
Composition of saliva
Saliva contains 99.4% water and 0.6 solids. The saliva has a pH of 6.8 (natural,
slightly acidic) which necessary for working of amylase.
Saliva contains two major types of protein (two thirds of total solids, 0.4%):
a- α-amylase which is an enzyme for digesting starch
b- Mucin (glycoprotein) for lubricating purposes
It is also contains some inorganic ions (one third of total solid 0.2%) such as
Na+, K+, Ca++, PO4, Cl-, I, - SCN (in the smokers) and HCO3-
Function of Saliva
1- Digestive role, catalysing hydrolysis of polysaccharide (starch and
glycogen) into dextrin and disaccharide (maltose_
2- Lubricating of food (due to mucin, which is an excellent compound that
facilitates passage of food through G.I.T.
3- For testing
4- Neutralization influence upon some of the acidity of the stomach (due to
the presence of machinery and bicarbonate ions)
The presence of stone in slivery gland because of presence of NaCl and other
salts that precipitate and blockage of silvery gland
- α-amylase hydrolase only α 1-4 bonds such as the bonds in starch, it
cannot hydrolyse β (1-4) like in cellulose
- Some people have acidic pH of saliva because of the presence of organic
acid (lactic acid)in their saliva as a result from the bacteria found in the
carries of the teeth
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Esophagus
The esophageal secretions are entirely mucoid in character and principally
provide lubrication for swallowing. The food passes to stomach through the
peristaltic movement of the esophagus. No digestive juice is secreted in the
esophagus, but amylase of the saliva continues its activity during this passage
Stomach
The main digestion of protein takes place in the stomach. The digestion of
carbohydrates and fats is stopped due to the presence of HCl (high acidity).
Gastric secretion is initiated by nervous or reflex mechanism; effective stimuli
are similar to those of salivary secretion. Secretion is due to hormonal stimulus
gastrin, which produced by gastric glands
The gastric juice, which is a mixture of HCl, organic material (enzymes)
secreted from the gastric gland, which is composed of 3 types of cells:
1- Columnar cells: present in the neck of gastric gland, secret mucin
2- Parietal cells: found in the tubular part of gastric gland, arranged in
layers, secrete HCl
3- Chief cells: these are exhibiting a single layer of secreting cells in the
neck of gastric gland, secrete HCl, pepsin and other enzymes
Function of gastric mucin:
a- Protect epithelial tissue from being digested, through its buffering action
of the gastric juice to protect the stomach wall from the action of HCl and
pepsin and prevents the formation of gastric ulcers
b- Provide us with glycoprotein called intrinsic factor that facilitates
absorption of Vit. B12
The most common cause of maturation failure is not lack of Vit B12 in the
diet, but instead failed to absorb Vit B12 from the G.I.T. This often occurs
in the disease called pernicious (malignant) anemia
Stimulation of gastric secretion
The factors stimulate gastric juice in 3 phases:
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a- Cephalic phase: includes the taste, smell and sight of foods
b- Gastric phase: includes the presence of food in the stomach, this
stimulation due to mechanical and chemical factors which cause the wall
of the stomach to secrete hormone called gastrin carried by the blood to
the parietal cells of gastric gland to the wall and cause HCl secretion
Histamine: also stimulates the secretion of HCl (like gastrin) but has a
different structure (produced from removal of CO2 from histidine)
c- Intestinal phase: presence of food in the duodenum of intestine stimulates
secretion of gastric juice, which is due to hormonal stimulation
The composition of gastric juice
- Colourless clear fluid and contain about (99.4% water), 0.6% total
solids
- Chief inorganic substances in gastric juice are HCl and small amounts
of NaCl, KCl, PO4-3
- The organic substances are enzymes:
a- Pepsin
It is produced in the peptic and mucous cells of the gastric glands, and
secreted as inactive form pepsinogen and in the cavity it is activated as it
come in contact with HCl formed pepsin that cataylase the conversion of
protein into polypeptides, proteoses and small particles
b-Renine
This enzyme is in the infant stomach only and facilitate the digestion of
casine of milk and this enzyme after 6 months of age will disappear (it
absent in adult)
c-Lipase
Which is inactive because of low pH, it has minor lipolytic influence
when compared with pancreatic and intestinal lipase (hydrolyse
triglycerides of short and medium chain length)
Hydrochloric acid (HCl)
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The parietal cells are the main source of HCl. These cells contain the enzyme
carbonic anhydrase, which catalyses the reversible reaction of CO2 with H2O to
carbonic acid
The HCl conc=170 meq/L pH=0.87 and normality of 0.17 N
Davenport theory: according to this theory, plasma CO2 can pass through
parietal cells freely. The solubility of CO2 is very low in normal conditions, but
by the action of carbonic anhydrase the solubility becomes 100 times more
soluble. H2CO3 will then dissociate to give bicarbonate + H+ions. The hydrogen
ion in some way is secreted and accompanied with Cl- which is from lymph to
form HCl. H2O get out, HCO3 is absorbed into the blood the bicarbonate ions
go to the lymph to replace the Cl- ions taken
The membrane adjacent to the gastric lumen secretes H+ & Cl.- The HCO3
formed within the cell is passed back to plasma. The Cl- is freely permeable
membranes so Cl- comes from plasma enters the cell and then secreted into the
lumen.
HCO3- will combine with Na+ to form NaHCO3 and increases slightly the pH of
the blood, the buffering system of blood, neutralize this alkalinity, then pass
away in the urine,i.e. urine will be less acidic.
The hydrogen ion needed may come from the following methods:
1- The dissociation of H2CO3 as follows
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2- It may also come from glucose metabolism within mitochondria
3- Or the dissociation of water
as result of contact with gastric HCl, proteins are denatured
(destruction)this allows the polypeptide chain to unfold, making it more
accessible to the action of proteolytic enzymes. The low pH also has the
effect of destroying most microorganism entering G.I.T
Clinical investigation of gastric function
The highly acid nature of gastric juice predisposes to the formation of nonhealing ulcer or slowly healing ulcer in the stomach known as “peptic ulcer” or
in the duodenum “duodenal ulcer”
- Hyperacidity (hyper chlorohydria): acidity may be associated with
hypermotility and rapid emptying of the stomach. This is seen in patients
suffering from a duodenal ulcer due to a state of irritation of the lining
mucosal membrane. The secretary phase increase secreting high amount
of HCl
- Hypoacidity (hypochlorohydria): this take place in gastric juice
obstruction in patients of chronic illness of the stomach associated with
atrophic changes in the gastric lining of the stomach such as chronic
gastritis and gastric ulcer.
- Achlohydria: when there is no HCl secretion, this is a diagnostic feature
of stomach cancer; there might be detected of acidity, but due to organic
acids as lactic acid or butyric acid due to fermentation by bacterial flora.
i.e. , bacteria can act only in the absence of HCl.
Function of HCl
1234-
Activates pepsinogen
Provides optimum pH for the action of pepsin(acidic medium)
Denaturates protein , become easily digested
Facilitates absorption of iron, its deficiency causes anaemia
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5- Because of its high acidity, it acts as a germicide, that kills pathogenic
bacteria
Note
Factors inhibit gastric secretion
1- fat presents in large amount in stomach (fatty meal)
2- fat present in the duodenum which gastric secretion and HCl
due to:
a- it decreases gastric motality
b- fat cause the release of hormone called enterogastrone
released by duodenal mucosa thus gastric juice and HCl
secretion is inhabited
Pancreatic Juice
It is a clear, watery secretion. It contains (1.5% total solids &98. 5 % water). It
has a pH of (8.0-8.3, which is alkaline) depends upon HCO3- concentration.
Amount of secreted per day is about (1000 cc) depend on the amount and type
of diet.
Two thirds of total solids which is equivalent to 1% is organic material and
consist mainly of enzymes. Some of these enzymes secreted as zymogens
(trypsine, chemotrypsine and procarboxypeptidase) inactive forms which are
secreted by pancreases, when reach duodenum, they are activated by an enzyme
of intestinal wall called entrokinase. The activation involves hydrolytic removal
of a small peptide from the inactive enzymes. Once active trypsine is produced
thus in small amounts, it can activate the rest of trypsinogen
&chymotrypsinogen (auto catalysis)
Carboxyepeptidase secreted probably as aprocarboxyypeptide which
is inactive form and activated by trypsin, it acts on the carboxyl group
of amino acid in the polypeptides
Function of trypsin
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biochemistry
Dr. Anwar j almzaiel
Protein digestion
Auto catalysis
Chymotrypsinogen activation
Procarboxy peptide activation
4. Lipase: hydrolyse lipid into glycerol or fatty acid and monoglycerides
5. Amylase: which hydrolyse α1-4 glycosidic linkages in polysaccharides (like
starch into amylopectine or glycogen into maltose)
6. Cholesterol esterase: hydrolyse cholesterolester into cholesterol and fatty
acids
7. Ribonuclease:hydrolyse ribonucleic acid (RNA) into nucleotides
8. Deoxyribonuclease:hydrolyse deaoxyribonucleic acid(DNA) into
nucleotides
9. Collagenase: hydrolyse collagen in diet (muscle &tissue)
10. Phosphatase: can remove phosphate from organic substances
All these enzymes act in either neutral or slightly alkaline
One third of the solid (0.5%) is inorganic material & consist mainly of the Cl - &
HCO3- and Na+ . They function to neutralize the HCl action in stomach
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& provide alkaline pH for the action of these enzymes which act on
neutral or alkaline media.
The other inorganic materials which present in small amounts K+, Ca+
& PO4+
Secreted from different intestinal glands in mucosa at intestinal and
duodenum from the gland called Brunner LieberKuhn gland. The juice
contains desquamated epithelial cells, leukocytes and mucus. Intestinal
juice contains 98.5% water and 1.5% total solids.
The organic solids contain enzymes, musin, phosphate lipids and
enzyme like substances, pH= 7.0-8.0
The enzymes are:
1- Nucleotidase: hydrolse the nucleotide into nucleoside with PO4-3
Nucleotide: nitrogen base, ribose & phosphoric acid
Nucleoside: nitrogen base and ribose only
2- Nucleosidase: converts nucleoside to nitrogen base & pentose
sugar (ribose)
3- Maltase: converts maltose to 2 molecules of glucose
4- lactase: converts lactose to glucose and galactose
5- Sucrase: converts sucrose to glucose and fructose
6- Amino peptidase: hydrolyze the polypeptide release amino of the
polypeptide to dipeptide
7- Dipeptidase: hydrolyze the didpeptide into a.a.(amino acids)
8- phospholipases: convert the phospholipid to fatty acids (saturated
& unsaturated), PO4- , glycerol and nitrogen
9- Phosphatases: remove the phosphate group from organic
compound & phosphate will be available to be absorbed the
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inorganic solid (Na+, Cl-, HCO3-, K+, Ca++, PO4-3) are similar as that
found in the pancreatic juice
The intestinal juice secretion is stimulated by hormone called
‘Enterocrinin’ which is produced from Duodenum & jejunum
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Bile is secreted in the small intestine; it isn’t digestive secretion
& contains no enzymes but help in digestion, secreted at site of
pancreatic juice. It helps in digestion of fat and its absorption.
Bile is secreted by the liver and collected in the gall bladder,
stored & undergoes concentration; therefore we’ve bile with its
main constituents of organic material which is bile pigment,
mucin, cholesterol, bile acids and salts. Bile acids may increase
when we have inflammation in stomach or gall bladders, its
increased in the blood of liver in case of cancer, so bile acids
are marker if there’s any damage in the gall bladder of liver or
any change in bile itself
The volume secreted per day 500-1000 ml
The bile acids are cholic acids; there are 3 types of bile acids:
- Cholic acid
- Deoxycholic acid
- lithocholic acid
These cholic acids are conjugated with a.a like
Tyrosine
tyrocholic acid
or may be conjugated with a.a. like glycine
glycine
glycocholic acid
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biochemistry
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These are known as bile salt, these bile acids and salts
are synthesized by liver from cholesterol by oxidation of
the side chain of the molecule to give cholic acid, and they
are soluble in water.
Function of bile salt
1- Breakdown protein molecule to very small particles
2- Increase surface area of fat molecules to be acted by enzyme
lipase for digestion of fat.
3- Highly emulsion agents, breakdown fat molecules into small
particles and decrease the surface tension of water, thus
increase the surface area of fat molecule to be acted by
enzyme lipase for digestion of fat
4- Facilitate the action of pancreatic lipase by shifting pH to be
optimum for lipase activity (6.5-8)
5- They form miscells with fatty acids & mono and diglycerides
6- It stimulates intestinal peristalsis (movement of intestine) help in
absorption of diet and pass of feces
7- Stimulate the liver to produce and synthesize of bile, this is due
to the mechanism by the action of hormones
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