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DIGESTION, ABSORPTION,
AND EXCRETION OF
PROTEINS
ANAGHA NAIR
PART II, MSc Biochemistry
INTRODUCTION
• William Beaumont, William Prout, Theodor
Schwann and Claude Bernard
• Essential and Non essential amino acids
• Animal and Plant based sources
• Daily protein load sources
• 1g of Protein: 4 calories
• Current RDA: 0.8 g per kg of body weight
• More required in pregnant women and Children
• Protein quality and Protein Density
• Constant breakdown and replacement of the
proteins
INTRODUCTION
• Peptidases:
• For protein digestion, most of proteases are secreted in inactive forms called pro-enzymes. If
they were synthesized in active forms, they would have hydrolysed cellular and extracellular
proteins of the organism itself. Inactive pro-enzymes are activated at the sites of their actions by
specific proteases or by optimal pH changes.
• Role of cooking in protein digestion
Exopeptidase
s
Endopeptidas
es
PROTEIN DIGESTION
1 – PROTEIN DIGESTION IN THE MOUTH
• Mechanical breakdown- Homogenization
• Role of the saliva
• No proteolytic enzymes
PROTEIN DIGESTION
2 – PROTEIN DIGESTION IN THE STOMACH
• Beginning of Hydrolysis- Partial digestion
• Release of Gastrin
• Stomach acidity and protein denaturation
• Mechanical and chemical digestion
• ATP dependant proton pump on luminal membrane and Histamine acting on H2 receptors on
Parietal cells
• Gastric acid: Pepsinogen activation by strong acidic pH, Activation of prosecretin and Antiseptic
• Pepsin: Non specific Partial digestion
• Peristalsis and chyme formation
• Secretin release by Duodenum and Cholecystokinin by
Duodenum and jejunum
• The Pancreatic proteases are secreted in inactive forms
like trypsinogen, chymotrypsinogen, proelastase
(endopeptidases) (Catalytic triad: Ser, His, Asp) and
procarboxypeptidase A and B (exopeptidases)
(Metalloezymes- Zn2+). The pancreas secretes digestive
juices and Bicarbonate buffer into the small intestine
• Activation of protease cascade by the Enterokinase
• Role of intestinal juices: Enteropeptidase, Dipeptidase and
Aminopeptidases
PROTEIN DIGESTION
3 – PROTEIN DIGESTION IN THE SMALL INTESTINE AND
PANCREAS
PROTEIN DIGESTION
• End products of Digestion: Free amino
acids, Dipeptides and tripeptides
• Absorption takes place in the ileum and
Jejunum of the small intestine.
• No absorption for peptides longer than 4
• Small intestine- microvilli
• Aminopeptidase-N
• Carrier proteins used for the absorption;
specific for each amino acid group
• Amino acid transporters in the luminal
membrane: Active Transport
ABSORPTION
• Release of the free amino acids into the bloodstream
• Transporters in the contraluminal membrane: Release into the blood stream
• Access to the interstitial fluids by endocytosis
• Mechanisms of Amino Acid absorption:
ABSORPTION
Sodium Dependent Active Transport: Movement of Na+ along the concentration gradient in the
intestinal cells via Na+ K+ ATPase.
Co-transportation of Dipeptides and Tripeptides by the proton electrochemical gradient across
the membrane: The dipeptide transporter also plays a key role in the absorption of Aminopenicillins
across the membrane
Meister Cycle: Aka gamma Glutamyl cycle. Involves tripeptides Glutathione (Gamma glutamyl cysteinyl
glycine). 1 Amino acid transfer= 3 ATP (consumed). Transport of certain amino acids like Cys and Glu.
Operated Sparingly.
o Transportation to the liver once the amino acids are in the blood.
o As with other macronutrients, the liver is the checkpoint for amino acid distribution and any further
breakdown of amino acids, which is very minimal.
o Dietary amino acids then become part of the body’s amino acid pool.
o Assuming the body has enough glucose and other sources of energy, those amino acids will be used in one of
the following ways:
•Protein synthesis
•Making nonessential amino acids
•Making other nitrogen-containing compounds
•Rearranged and stored as fat (there is no storage form of protein)
o If there is not enough glucose or energy available, amino acids can also be used in one of these ways:
•Rearranged into glucose for fuel for the brain and red blood cells: The nitrogen is removed in a process
called as Transamination and Oxidative deamination and the ammonia is transformed to Urea (excreted as
urine and highly soluble) due to toxicity. which occurs in the liver and kidneys
•Metabolized as fuel, for an immediate source of ATP
• What happens to the absorbed amino acids?
ABSORPTION
PepT1
 The gut and the liver utilize most of the absorbed amino acids.
 Glutamate and aspartate: Utilized as fuels by the gut, and very little enters the portal vein. The gut may also
use some branched chain amino acids. The liver takes up 60 - 70% of the amino acids in the portal vein of
which the most are converted to glucose.
 The increased levels of dietary amino acids reaching the pancreas stimulate the release of glucagon thereby
increasing amino acid uptake into the liver. Glucagon causes increased expression of amino acid transporters
on the liver cell surface
 Amino acids are deaminated in the liver and carbon skeletons are used for gluconeogenesis.
 Urea production increases to eliminate the nitrogen. Arg is a positive regulator of the first enzyme of the urea
cycle, carbamoyl phosphate synthetase I by stimulating the synthesis of N-acetyl glutamate, which stimulates
carbamoyl phosphate synthetase I
 Insulin release is also stimulated and net protein synthesis is stimulated, but gluconeogenesis in the liver is
not inhibited.
 Most of the amino acid nitrogen entering the peripheral circulation after a high protein meal or a mixed meal is
WHAT HAPPENS AFTER A PROTEIN RICH MEAL?
EXCRETION
• Nitrogenous waste products: Urine
• The average ratio of protein/nitrogen, by
weight, is 6.25, for the typical protein in the
diet.
• Normal urinary protein excretion is < 150
mg/day and consists mostly of secreted
proteins such as Tamm-Horsfall proteins
(Uromodulin).
• The normal mean albumin excretion rate
(AER): 5-10 mg/day (AER> 30 mg/day:
abnormal)
• Role of Proteinuria in identification of
kidney damage, worsening kidney disease
 Pancreatitis: Premature activation of pancreatic zymogens.
Serum amylase measured.
 Hartnup Disease: Defective absorption of neutral amino acids
(especially Trp). Defective transport across the intestinal
epithelium calls and reabsorption in renal tubular cells
resulting in neutral amino aciduria. Pellagra like symptoms
observed due to the loss of Trp. It may also be due to the non
availability of the Trp for Conversion of Niacin coenzymes.
DISEASES
Acute Pancreatitis Chronic Pancreatitis
 Protein Intolerance: Inflammation and swelling will occur in your intestines leading to gas,
diarrhea, stomach pain, cramping, bloating and nausea.
 Protein Allergy: Nausea, vomiting, diarrhea, stomach cramping, abdominal pain, gas and
bloating. Other symptoms that may develop include rashes, shortness of breath, wheezing,
coughing, nasal congestion, headaches, hives and facial swelling. Some food allergies can result
in a severe reaction that can lead to death.
 Diets high in animal protein especially red meat, are linked to a higher risk for kidney stones,
kidney disease, liver malfunction, colorectal cancer, and osteoporosis. Some scientists
hypothesize that high-protein diets may accelerate bone-tissue loss because under some
conditions the acids in protein block absorption of calcium in the gut, and, once in the blood,
amino acids promote calcium loss from bone; however even these effects have not been
consistently observed in scientific studies.
DISEASES
Nutritional Biochemistry- Tom Brody
Protein Digestion and Absorption – Nutrition: Science and Everyday Application, v. 1.0
(pressbooks.pub)
5.4: Protein Digestion, Absorption and Metabolism - Medicine LibreTexts
CRANE CW. Some aspects of protein digestion and absorption in health and disease. Postgrad
Med J. 1961 Dec;37(434):745-54. doi: 10.1136/pgmj.37.434.745. PMID: 13882022; PMCID:
PMC2482598.
Protein Digestion – Biology for Everybody (homeomagnet.com)
Protein digestion in the stomach and small intestine - Tuscany Diet (tuscany-diet.net)
How will Absorption and Assimilation of Proteins in the Human body? (takshilalearning.com)
REFERENCES:
PROTEINS DIGESTION, ABSORPTION.pptx

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PROTEINS DIGESTION, ABSORPTION.pptx

  • 1. DIGESTION, ABSORPTION, AND EXCRETION OF PROTEINS ANAGHA NAIR PART II, MSc Biochemistry
  • 2. INTRODUCTION • William Beaumont, William Prout, Theodor Schwann and Claude Bernard • Essential and Non essential amino acids • Animal and Plant based sources • Daily protein load sources • 1g of Protein: 4 calories • Current RDA: 0.8 g per kg of body weight • More required in pregnant women and Children • Protein quality and Protein Density • Constant breakdown and replacement of the proteins
  • 3. INTRODUCTION • Peptidases: • For protein digestion, most of proteases are secreted in inactive forms called pro-enzymes. If they were synthesized in active forms, they would have hydrolysed cellular and extracellular proteins of the organism itself. Inactive pro-enzymes are activated at the sites of their actions by specific proteases or by optimal pH changes. • Role of cooking in protein digestion Exopeptidase s Endopeptidas es
  • 4. PROTEIN DIGESTION 1 – PROTEIN DIGESTION IN THE MOUTH • Mechanical breakdown- Homogenization • Role of the saliva • No proteolytic enzymes
  • 5. PROTEIN DIGESTION 2 – PROTEIN DIGESTION IN THE STOMACH • Beginning of Hydrolysis- Partial digestion • Release of Gastrin • Stomach acidity and protein denaturation • Mechanical and chemical digestion • ATP dependant proton pump on luminal membrane and Histamine acting on H2 receptors on Parietal cells • Gastric acid: Pepsinogen activation by strong acidic pH, Activation of prosecretin and Antiseptic • Pepsin: Non specific Partial digestion • Peristalsis and chyme formation
  • 6. • Secretin release by Duodenum and Cholecystokinin by Duodenum and jejunum • The Pancreatic proteases are secreted in inactive forms like trypsinogen, chymotrypsinogen, proelastase (endopeptidases) (Catalytic triad: Ser, His, Asp) and procarboxypeptidase A and B (exopeptidases) (Metalloezymes- Zn2+). The pancreas secretes digestive juices and Bicarbonate buffer into the small intestine • Activation of protease cascade by the Enterokinase • Role of intestinal juices: Enteropeptidase, Dipeptidase and Aminopeptidases PROTEIN DIGESTION 3 – PROTEIN DIGESTION IN THE SMALL INTESTINE AND PANCREAS
  • 8. • End products of Digestion: Free amino acids, Dipeptides and tripeptides • Absorption takes place in the ileum and Jejunum of the small intestine. • No absorption for peptides longer than 4 • Small intestine- microvilli • Aminopeptidase-N • Carrier proteins used for the absorption; specific for each amino acid group • Amino acid transporters in the luminal membrane: Active Transport ABSORPTION
  • 9. • Release of the free amino acids into the bloodstream • Transporters in the contraluminal membrane: Release into the blood stream • Access to the interstitial fluids by endocytosis • Mechanisms of Amino Acid absorption: ABSORPTION Sodium Dependent Active Transport: Movement of Na+ along the concentration gradient in the intestinal cells via Na+ K+ ATPase. Co-transportation of Dipeptides and Tripeptides by the proton electrochemical gradient across the membrane: The dipeptide transporter also plays a key role in the absorption of Aminopenicillins across the membrane Meister Cycle: Aka gamma Glutamyl cycle. Involves tripeptides Glutathione (Gamma glutamyl cysteinyl glycine). 1 Amino acid transfer= 3 ATP (consumed). Transport of certain amino acids like Cys and Glu. Operated Sparingly.
  • 10. o Transportation to the liver once the amino acids are in the blood. o As with other macronutrients, the liver is the checkpoint for amino acid distribution and any further breakdown of amino acids, which is very minimal. o Dietary amino acids then become part of the body’s amino acid pool. o Assuming the body has enough glucose and other sources of energy, those amino acids will be used in one of the following ways: •Protein synthesis •Making nonessential amino acids •Making other nitrogen-containing compounds •Rearranged and stored as fat (there is no storage form of protein) o If there is not enough glucose or energy available, amino acids can also be used in one of these ways: •Rearranged into glucose for fuel for the brain and red blood cells: The nitrogen is removed in a process called as Transamination and Oxidative deamination and the ammonia is transformed to Urea (excreted as urine and highly soluble) due to toxicity. which occurs in the liver and kidneys •Metabolized as fuel, for an immediate source of ATP • What happens to the absorbed amino acids?
  • 12.  The gut and the liver utilize most of the absorbed amino acids.  Glutamate and aspartate: Utilized as fuels by the gut, and very little enters the portal vein. The gut may also use some branched chain amino acids. The liver takes up 60 - 70% of the amino acids in the portal vein of which the most are converted to glucose.  The increased levels of dietary amino acids reaching the pancreas stimulate the release of glucagon thereby increasing amino acid uptake into the liver. Glucagon causes increased expression of amino acid transporters on the liver cell surface  Amino acids are deaminated in the liver and carbon skeletons are used for gluconeogenesis.  Urea production increases to eliminate the nitrogen. Arg is a positive regulator of the first enzyme of the urea cycle, carbamoyl phosphate synthetase I by stimulating the synthesis of N-acetyl glutamate, which stimulates carbamoyl phosphate synthetase I  Insulin release is also stimulated and net protein synthesis is stimulated, but gluconeogenesis in the liver is not inhibited.  Most of the amino acid nitrogen entering the peripheral circulation after a high protein meal or a mixed meal is WHAT HAPPENS AFTER A PROTEIN RICH MEAL?
  • 13. EXCRETION • Nitrogenous waste products: Urine • The average ratio of protein/nitrogen, by weight, is 6.25, for the typical protein in the diet. • Normal urinary protein excretion is < 150 mg/day and consists mostly of secreted proteins such as Tamm-Horsfall proteins (Uromodulin). • The normal mean albumin excretion rate (AER): 5-10 mg/day (AER> 30 mg/day: abnormal) • Role of Proteinuria in identification of kidney damage, worsening kidney disease
  • 14.  Pancreatitis: Premature activation of pancreatic zymogens. Serum amylase measured.  Hartnup Disease: Defective absorption of neutral amino acids (especially Trp). Defective transport across the intestinal epithelium calls and reabsorption in renal tubular cells resulting in neutral amino aciduria. Pellagra like symptoms observed due to the loss of Trp. It may also be due to the non availability of the Trp for Conversion of Niacin coenzymes. DISEASES Acute Pancreatitis Chronic Pancreatitis
  • 15.  Protein Intolerance: Inflammation and swelling will occur in your intestines leading to gas, diarrhea, stomach pain, cramping, bloating and nausea.  Protein Allergy: Nausea, vomiting, diarrhea, stomach cramping, abdominal pain, gas and bloating. Other symptoms that may develop include rashes, shortness of breath, wheezing, coughing, nasal congestion, headaches, hives and facial swelling. Some food allergies can result in a severe reaction that can lead to death.  Diets high in animal protein especially red meat, are linked to a higher risk for kidney stones, kidney disease, liver malfunction, colorectal cancer, and osteoporosis. Some scientists hypothesize that high-protein diets may accelerate bone-tissue loss because under some conditions the acids in protein block absorption of calcium in the gut, and, once in the blood, amino acids promote calcium loss from bone; however even these effects have not been consistently observed in scientific studies. DISEASES
  • 16. Nutritional Biochemistry- Tom Brody Protein Digestion and Absorption – Nutrition: Science and Everyday Application, v. 1.0 (pressbooks.pub) 5.4: Protein Digestion, Absorption and Metabolism - Medicine LibreTexts CRANE CW. Some aspects of protein digestion and absorption in health and disease. Postgrad Med J. 1961 Dec;37(434):745-54. doi: 10.1136/pgmj.37.434.745. PMID: 13882022; PMCID: PMC2482598. Protein Digestion – Biology for Everybody (homeomagnet.com) Protein digestion in the stomach and small intestine - Tuscany Diet (tuscany-diet.net) How will Absorption and Assimilation of Proteins in the Human body? (takshilalearning.com) REFERENCES: