BIOCHEMISTRY OF GASTROINTESTINAL SYSTEM

Objectives
 At the end of this lesson You will able to describe
Digestion and absorption of food
 The effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
Liver Metabolism
Liver function tests
Bilirubin, ALT,AST,ALP,GGT
GGT, Urea, NH3 and Albumin
 Pancreatic function tests

BIOCHEMISTRY OF GASTROINTESTINAL SYSTEM
Definitions
 Food: - is any solid or liquid which ingested & enable the body to carry out any of its
life function.
 Nutrients; Foods components which provide energy and serve as cofactor in different
metabolic reactions
 Xenobiotic: Biologically unimportant components which excrete with wastes are
 Roughage: - is as dietary fibers which enable the body to get rid of waste products,
which would otherwise become poisonous to the body.
3

Macronutrients Contribute to the Energy Pool of the Body
and Micronutrients are Cofactors (Coenzymes):
Energy Pool
of the body
(100%)
28 March
2023
4
Micronutrient
(Vitamins, ions)<0.01%)
Fats
20% - 35%
Proteins
(10% - 35%)
Macronutrients

BIOCHEMISTRY OF GASTROINTESTINAL SYSTEM Cont…
 Food have a little chemical different from the tissue of the animal
 So how tissues of animal protected from enzymatic digestion?

BIOCHEMISTRY OF GASTROINTESTINAL SYSTEM Cont…
 GIT biochemistry discuss the role of GIT in peripheral energy homeostasis through
digestion, assimilation and absorption of ingested nutrients.
 The whole process of digestion involves hydrolytic cleavage reactions with the final
absorbable monomers like:
Monosaccharaides, amino acids, fatty acids and glycerol
 Tissue of the animal protected from enzymatic digestion by:
 Secretion of most digestive enzymes in the form of Zymogen and
 Capsulation of tissues with mucus (large glycoproteins)
6

Strategies that prevent premature zymogen activation
 Secretion of most digestive enzymes in the form of Zymogen
Capsulation of tissues with mucus (large glycoproteins)
At pH>2, the peptide (44 AA) clipped of pepsinogen remains bound to pepsin,
masking its active site; it is released by a drop of pH below 2 or by further degradation
by pepsin
Acinar cells synthesize and secrete a trypsin inhibitor that acts as a safeguard
against trypsin activation within the pancreas.
Pancreatic secretory trypsin inhibitor (PSTI), a small polypeptide, blocks any
trypsin that is erroneously activated within the pancreas
Another protective mechanism is that trypsin has a mechanism of autolysis (self-digestion)
Fluid secretion by duct cells flush zymogens/active enzymes out of the pancreas into
the duodenum
α-1ant trypsin blocks any trypsin that is erroneously activated within the alveoli

BIOCHEMISTRY OF GASTROINTESTINAL SYSTEM Cont…
The Characteristics of Most Digestive Enzymes
They are fairly narrow substrate specificity; e.g.
Glycosidase (glycosidic bonds), proteases/peptidase (peptide bonds),
Lipases (ester bonds) and Nucleases(phospodiester bond)
They hydrolyzes only specific bonds based on the type of nutrients; e.g.
 Salivary amylase (α-1→ 4 glycosidic bonds)
 Isomaltase (α-1→ 6 glycosidic bonds)
 Surcease (α-1→ 2 glycosidic bonds)
 Lactase (β-1→ 4 glycosidic bonds)
PH specific

Salivary --amylase
Lingua lipase
 HCL, Gastric lipase, pepsin, rennin
Pancreatic -amylase and HCO3-
Pancreatic lipase. Co-lipase, phospholipase & cholesterol esterase
Trypsinogen, chymotrypsinogen, proelastase and procarboxypeptidse
 Glucoamylase, Lactase, Sucrase &Trehalase
Enterokinase. Aminopeptidase, dipeptidase &
tripeptidase
Bile acid/salt

Mechanisms of Carbohydrate Absorption
A. Sodium-dependent transport
B. Sodium-independent transport (GLUTs)
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Lipid Digestion and Absorption
11

Protein Digestion and Amino Acids Absorption
12

 Sodium-dependent transport and facilitated
diffusion.
13
Absorption of Amino
Acids

The Effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
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 Gastrin
 Motilin
 Secretin
 PYY
 PP
 CCK
 Ghrelin
 GLP-1
 GIP

The Effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
 In addition to insulin and the counter regulatory hormones variety of peptides influence
fuel metabolism
 The following Gut” hormones have indirect influence on fuel metabolism by effects on
the synthesis or secretion of insulin or the counter hormones.
 For example:
 Gastrin induces gastric acid secretion, which affects nutrient digestion & absorption .
 Secretin stimulates pancreatic and biliary bicarbonate and water secretion but inhibits
gastrin release and secretion of gastric acid
 Peptide YY (PYY) inhibits gastric acid secretion, slows intestinal motility and inhibits

The Effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
 For example:
 Motilin stimulates gastric and pancreatic enzyme secretion to influences nutrient
digestion and Induces gallbladder contraction
 Pancreatic polypeptide (PP) reduces gastric emptying &slows upper intestinal motility
 CCK inhibits proximal gastric motility to increases postprandial satiety &regulates
nutrient-stimulated pancreatic enzyme secretion & gallbladder contraction
 Ghrelin, is growth hormone secretagogue & appetite stimulant. Its mechanism is
through the activation of the AMPK in the hypothalamus which leads to the release of
neuropeptide Y, which increases appetite. Research geared toward interrupting the
ghrelin/ghrelin receptor signaling system is increasing to develop new antiobesity agents.

The Effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
 “INCRETIN” are all Insulinotropic factors from GIT which potentiating insulin release
from β-pancreatic cell
INCRETIN do not act as direct insulin secretagogues, they have indirect influence
through fuel metabolism
 They are mediating modest postprandial (After a meal) increase in serum glucose by
slowing gastric empty time and increase the rate of insulin synthesis and secretion
INCRETIN are accounted for the greater β-cell response(50-70%) seen after an oral
glucose load as opposed to that seen after the administration of glucose intravenously

The Effect of Gastrointestinal-Derived Hormones on Fuel Metabolism
Several gastrointestinal peptides have INCRETIN effect , e.g.;
 Glucagon like peptide-1 (GLP-1) regulate glucose homeostasis by inhibiting the
secretion of glucagon
 Glucose-dependent insulinotropic polypeptide (GIP) interacts with GIP receptors
on adipocytes, this interaction coupled to energy storage
The half-lives of GIP and GLP-1 in the circulation are on the order of 2.5 minutes.
The protease DPP-4 (dipeptidyl protease 4) found on the surface of kidneys,
intestine, liver, and many other tissues is responsible for inactivating GIP and GLP-1.
If one wants to increase the efficacy of the incretins (GIP/GLP-1):
synthetic incretin which mimics GIP/GLP-1 & with longer half-lives could be developed along
with drugs which inhibit DPP-4, thereby increasing the serum half-lives of GIP and GLP-1.
Such synthetic incretin/drugs have been developed & are used for treatment of type 2 DM

Liver Metabolism

LIVER METABOLISM
Because of its wide range and diversity of synthetic functions, the liver
may be considered to be the body’s factory,
Taking raw materials and producing many compounds, some of which
are exported for use in other tissues.

Liver Metabolism
Metabolic Functions
 Carbohydrate metabolism (glycogen
metabolism & gluconeogenesis
 Lipid metabolism (cholesterol, fatty acids &
TAG synthesis, bile and bile salt synthesis
 Detoxification (Urea cycle, Conjugation &excretion of
bilirubin),, gluconeogenesis from glycerol & lactate
(Cori cycle)
Vitamin storage vit. B 12, vit A and K
 All proteins synthesis except gamma globulin
Liver cells are responsible for conversion of
preprothrombin (inactive) to active prothrombin in
the presence of vit. K.
 It also produces other clotting factors like factor V,
VII and X. Fibrinogen involved in blood
coagulation is also synthesized in liver.
Right lobe Left lobe
Gall bladder Bile duct Pancreas

BLOOD
CELLS
LIVER
Bilirubin diglucuronide
(water-soluble)
2 UDP-glucuronic acid
via bile duct to intestines
Stercobilin
excreted in feces
Urobilinogen
formed by bacteria KIDNEY
Urobilin
excreted in urine
CO
Biliverdin IX
Heme oxygenase
O2
Bilirubin
(water-insoluble)
NADP+
NADPH
Biliverdin
reductase
Heme
Globin
Hemoglobin
reabsorbed
into blood
Bilirubin
(water-insoluble)
via blood to
the liver
INTESTINE
Catabolism of hemoglobin
unconjugated
3/28/2023
ORGANS
FUNCUTION
TEST
A
22
Detoxification(Conjugation and Excretion of Bilirubin)

LIVER METABOLISM
UREA CYCLE AND NH4 DETOXIFICATION
3/28/2023
23
ORGANS
FUNCUTION
TEST
A

Liver Metabolism
Detoxify Lactate Produced by Muscle and RBC through CORI CYCLE)
Gluconeogenesis
Glycolysis

Glucose-Alanine Cycle Detoxify NH3 from Muscles Proteins Degradation
Through UREA CYCLE During Starvation and Diabetes

Liver Metabolism
Only Liver blood glucose homeostasis through gluconeogenesis & glycogenolysis
Only Liver clear glycerol produced by adipose tissue TAG lipolysis

Liver Metabolism
Only in the Liver Ketogenesis (Ketone Bodies Synthesis occur)

Structure of Cholesterol & Regulation of Cholesterol Homeostasis by
Promoting Bile Acids and Bile Salts Synthesis in the Liver
 Bile acids are synthesized in the liver from cholesterol & stored in the gall bladder.
 About 15-30 grams/day of bile acids is secreted into the GIT through common bile duct.
CH3
CH3
HO
H3C CH3
CH3
A B
C D
1
2
3
4
5
6
7
8
9
10
11
12
13
14 15
16
17
18
19
20
21
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Structure of Primary Bile Acids

The Difference between Bile Acids Cholesterol :
 The rings in bile salts contain more OH groups (2/3) than cholesterol
The rings in bile salts contain less carbons (24-C) than cholesterol (27C)
Bile salts have a polar side chain (carboxylic acid (COOH) function group
Unlike cholesterol bile acids lack a C5–C6 double bond.

Functions of Bile
 The alkaline pH of the bile serves to neutralize the acidity of the gastric juice.
 The bile salts are efficient surfactants and detergents.
 Bile is the only route of excretion for bilirubin, the end product of heme catabolism.
 It serves to excrete cholesterol, thus regulating the body cholesterol pool.
 Bile serves as the medium of excretion for several drugs which are detoxified by liver
 Bile acids are emulsifier of lipids
 Bile acids promote absorption of fat and fat -soluble vitamins (A, D, E & K).
 They also maintain cholesterol homeostasis by promoting excretion of cholesterol
 i.e. extra cholesterol can be disposed as bile acids

Bile Acids synthesis and secretion serves as a major route to get rid of Cholesterol

Bile Acids synthesis and secretion serves as a major route to get rid of Cholesterol

Clinical Significance of Bile Salts Metabolism (Cholestasis
(Cholelithiasis))
 Cholelithiasis (the presence of stone in the gallbladder or bile duct) is caused by:
Decreased bile salts and phospholipid
 Increased cholesterol in the bile (>15%)
Cholecystitis (Infections of the gallbladder)
Dehydration
 Those type of bile is called Lithogenic bile (promoting the formation of calculi).
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LIVER FUNCTION TESTS

LIVER FUNCTION TESTS
 Liver function tests are a group of tests done to assess the functional capacity of the liver as well as any
cellular damage to the liver cells such as:
1.Its Synthetic ability: By measuring the various plasma proteins such as albumin and prothrombin
that are synthesized by the liver and PT
 The half-life of prothrombin is 6 hours only; therefore, PT indicates the present function of the liver.
 PT is prolonged only when liver loses more than 80% of its reserve capacity.
2. Liver Enzyme Panel: two types
1.Those indicating hepatocellular damage and
ALT, AST, GGT, LDH; AST may be more than ALT in alcoholic liver disease.
2. Those indicating cholestasis (obstruction): GGT used as major discriminate the source of elevated ALP
 If ALP is elevated parallel with GGT source of the elevated ALP is most likely biliary tract
3. Its secretory/excretory abilities: By measuring the serum bilirubin level

Liver Function Tests
Bilirubin (Total and direct bilirubin)-should be low in serum
Total protein (high)
Albumin (serum level should be high if it is normal),
Prothrombin time (shorter)
 Lipids profile (LDL, HDL, VLDL and TAG)
Ammonia and Urea: NH4 ----------> Urea
Liver Inflammatory enzymes: ALT, AST, ALP, GGT

PANCREATIC FUNCTION TESTS
Endocrine function (glucagon Insulin)
Exocrine function

PANCREATIC FUNCTION TESTS
 Disease of the pancreas
Diabetes Mellitus: hyperglycemia and glycosuria
Pancreatitis: Inflammation of pancreas
Malabsorption syndrome : Decreased acinar cell activity leading
to reduce digestive enzymes
Pancreatic carcinoma:

PANCREATIC FUNCTION TESTS
 Acute Pancreatitis
serum amylase
 Derived from pancreatic acinar cells
 amylase level rises over the first 2-12 hours, peaks at 48 hours, returns to normal
within 3-5 days
 Serum: 70 - 340 IU/L, Urine: up to 300 IU/L per hour
 Serum lipase
is derived from pancreatic acinar cells, it rises slightly earlier than amylase, 1-8 hours
peaks earlier, at 24 hours
The serum lipase also lasts longer in the serum, 8-14 days
Serum lipase is more sensitive and specific than the serum amylase
159 Reference : 0 - 62 U/L

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