Download MBBS Biochemistry PPT 62 Ingestion, Digestion And Absorption Of Dietary Lecture Notes

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Ingestion, Digestion & Absorption of Dietary

Proteins

Specific Learning Objectives

Describe importance of dietary protein quality in maintenance of health, and consequences of protein-energy malnutrition (e.g.

Marasmus and Kwashiorkor)

Describe role of gastric hormone gastrin and paracrine hormone histamine in promoting secretion of HCl and pepsinogen, and

activation of pepsinogen to pepsin.

Describe pepsin action in digestion of peptides
Describe roles of secretin, bicarbonate and cholecystokinin in neutralization of duodenal pH, and release of bile and pancreatic

zymogens

Describe activation of pancreatic zymogens and roles of active enzymes in protein digestion.
Ingestion of Dietary Proteins
Describe digestion of dietary proteins in stomach, duodenum and smal intestine
Describe uptake of peptides and aa from gastrointestinal tract
Discuss absorption and transport of aa to liver
Identify defects in uptake of aa (e.g. Hartnup disease) or peptides that lead to clinical symptoms (failure to thrive, edema,

various vitamin deficiencies).
Introduction

Dietary Protein consists of long chains of aa
In digestive process, enzymes in stomach and small intestine break

down complex protein into polypeptides and further into individual aa.

aa are absorbed through wall of small intestine, pass into blood and

further to liver through portal vein.

Ingestion of Dietary Proteins

Ingested dietary proteins is hydrolysed to aa

Absorbed from intestine and utilization of these aa for synthesis of body

proteins ex. structural proteins, plasma proteins, enzymes, milk proteins,

and hormones

Also synthesis of necessary non-protein nitrogen compounds includes

urea, uric acid, creatine, creatinine, aa, and polypeptides
Cont-

Recommended Dietary allowance (RDA) for both men and women: 0.8 g

of protein/kg body weight/day

Dietary proteins: Dietary proteins in our diet are either from animal source

or vegetable source.

Animal sources: Milk and dairy products, meat, fish and eggs.

Vegetable sources: Cereals, pulses, peas, beans and nuts

Importance of Dietary Proteins

For structural component of cells and tissues

Without adequate protein in diet, body cells and tissues would not be able

to function.

Proteins are large, complex molecules made up of smaller aa

compounds.
Cont-

Some aa are made by body and are nonessential, but others are

essential, meaning that we need to get them from diet

Therefore, consume protein-rich foods each day, since body does not

have a way to store amino acids

Cont--

? Essential

aa:

Cannot

be

synthesize in body so "essential"

to eat them from dietary food.

? Non-essential:

Body

can

synthesize them from other

proteins so not essential to eat

them

Table 27.1. Harper's Illustrated Biochemistry 30th Edition
Overview of the Digestion of Dietary Proteins

Marks, Marks and Smith, Medical Biochemistry

Digestion of Dietary Proteins

Proteins are too large to be absorbed by intestine, therefore, must be

hydrolysed into di- and tripeptides as well as individual aa, which can

be absorbed

Proteolytic enzymes responsible for degrading proteins are produced

by three different organs: stomach, pancreas, and small intestine
Activation of Gastric and Pancreatic zymogens

? Pepsinogen catalyzes its own

cleavage at pH of stomach

? Trypsinogen is cleaved by

enteropeptidase

? Active form of enzyme trypsin

plays a key role by catalysing

cleavage of other pancreatic

Marks, Marks and Smith, Medical Biochemistry

zymogens

Cont--

Digestion by gastric secretion: Digestion of proteins begins in stomach,

which secretes gastric juice, contains hydrochloric acid (HCl) and

proteolytic enzyme

Pepsin is a potent proteolytic enzyme and is present in gastric juices.
It is secreted as inactive zymogen form, pepsinogen.
Cont--

It is synthesised in "chief cells" of stomach

HCl maintains gastric pH at about 1 to 2 and ensures maximum

pepsin activity.

Optimum pH for pepsin is 1.6 to 2.5 and pepsin gets denatured if pH

is greater than 5.

Cont--

? Pepsinogen is hydrolysed in stomach

with help of HCl or pepsin itself

(autocatalytically) to form "active"

pepsin

? In process of activation (i) inactive

peptide called as "pepsin inhibitor

and (ii) 5 smaller peptides (inactive)

are liberated.
Cont--

Pepsin is a proteinase, a non-specific endopeptidase, and it hydrolyses

peptide bonds well inside protein molecule and produces proteoses and

peptones

It is particularly active on a peptide bond, which connects ?COOH group

of an aromatic aa like Phe, Tyr, and Tryp with amino group of either a

dicarboxylic acid or an aromatic a.a

Cont--

Pepsin also hydrolyse peptide bonds of:
? COOH group of methionine and leucine
? Leucine and glutamic acid
? Glutamic acid and asparagine
? Leucine and valine
? Valine and cysteine

Pepsin cannot act on proteins like keratins, Silkfibroins,

mucoproteins, mucoids and protamines
Digestion by pancreatic secretion

Optimum pH for activity of pancreatic enzymes (pH 8) provided by

alkaline bile and pancreatic juice

Secretion of pancreatic juice is stimulated by peptide hormones,

Cholecystokinin

Cont--

On entering small intestine, large polypeptides produced in stomach

by action of pepsin are cleaved to oligopeptides and aa by a group of

pancreatic proteases

Includes both endopeptidases (Trypsin, Chymotrypsin, Elastase) and

exopeptidases (metalloenzyme, contains zinc).
Digestion by proteolytic enzymes in intestinal juice

Amino-peptidases: Luminal surface of intestinal epithelial cells contains

aminopeptidase, an exopeptidase that repeatedly cleaves N-terminal

residue from oligopeptides to produce even smaller peptides and free

aa.

Requires presence of Zn++, Mn++ and Mg++ which help in formation

of a metal-enz-substrate coordination complex for catalysis

Cont--

Hydrolyse a terminal peptide bond connected to an end a.a bearing a

free- NH2 group, splits off end a.a. from N-terminal end of a

peptide, changing latter gradually stepwise to a "tripeptide"

Tri and Di-peptidases: hydrolyse peptides at either of two places
In microvil us membrane of intestinal epithelial cells, or inside

epithelial cells after peptides absorbed inside cell
Cont--

Tri-peptidase acts on a tri-peptide and produces a di-peptide and free

a.a

Di-peptidase hydrolyses a di-peptide to produce two molecules of aa

They require presence of Mn++, Co++ or Zn++ as cofactors for their

activity.

Cleavage of dietary protein in small intestine by pancreatic proteases

Peptide

bonds susceptible to

hydrolysis for each of five major

pancreatic proteases

? First

three

are

serine

endopeptidases, whereas the last

two are exopeptidases

Fig 19.5. Lippincott's Illustrated Reviews, Biochemistry, 6th Ed

Each is produced from an inactive

zymogen
Absorption of Amino Acids

Free aa are taken into enterocytes by a sodium-linked secondary

transport system of apical membrane.

Di- and tripeptides, are taken up by a proton-linked transport system.

Peptides are hydrolyzed in cytosol to aa that are released into portal

system by facilitated diffusion.

Cont--

Therefore, only free aa are found in portal vein after a meal

containing protein.

These aa are either metabolized by liver or released into general

circulation
Absorption of products of protein digestion by carrier protein transport system

? AA are absorbed into epithelial cells by Na+-

linked secondary transport via symporter

? Various aa are transported by carriers specific

for them

? AA exit cell at basal membrane via various

passive carriers by facilitated transporter

? AA enter blood by simple diffusion

Marks, Marks and Smith, Medical Biochemistry

Role of Glutathione in Amino Acid Absorption

Meister proposed that glutathione participates in an active group

translocation of L-amino acids (except L-Pro) into cells of small intestine,

kidneys, seminal vesicles, and brain.

He proposed a "cyclic" pathway/-glutamyl cycle in which Glutathione is

regenerated again

-glutamyl transferases (GGT) plays a key role in this cycle, a pathway for

synthesis and degradation of glutathione and drug and xenobiotic

detoxification
-glutamyl/Meister cycle

Fig.26.1: Text Book of Medical Biochemistry by Chatterjee & Rana Shinde, 8th Ed

Disorder related to aa transporter

Hartnup disease: Defect in SCL6A19 gene, it is a sodium-dependent and

chloride independent neutral aa transporter, expressed in kidneys and

intestine

This gene controls absorption of certain aa from intestine and

reabsorption of those aa in kidneys

Person with Hartnup disease cannot absorb aa properly from intestine

and cannot reabsorb them from tubules in kidneys
Cont--

Resulting excessive amount of aa such as Trp excreted in urine

Due to inadequate amount of Trp, body not able to make sufficient

amount of niacin (vit B3), which is necessary component of NAD+

Pellagra, a similar condition, is also caused by low nicotinamide; this

disorder results in dermatitis, diarrhea, and dementia

Cont--

Cystinuria: Dibasic (diamino aa) transporter Lys, Arg, Ornithine and

Cys. If there is any defect in this transport system, it leads to

Cystinuria

In medicine, Garrod's tetrad is a term named for British physician

Archibald Garrod, who introduced phrase "inborn errors of

metabolism" in a lecture in 1908

Tetrad comprises four inherited metabolic diseases: albinism,

alkaptonuria, Cystinuria and pentosuria
Intestinal aa transport systems and their disorders

Clinical-cases discussed
33

Reference Books

1) Biochemistry, Lippincott's Il ustrated Reviews, 6th Ed
2) Harper's Il ustrated Biochemistry-30th Ed
3) Lehninger Principles of Biochemistry, 6th Ed
4) Marks, Marks and Smith, Medical Biochemistry
5) Netter's Essential Biochemistry, 1st Ed

Thank you

This post was last modified on 05 April 2022