Protein metabolism

Dr.Mahr-un -nisa

Proteins

Proteins-----AA Proteins are made from 20 different amino

acids, 9 of which are essential. Each amino acid has an amino group, an

acid group, a hydrogen atom, and a side group.

It is the side group that makes each amino acid unique.

The sequence of amino acids in each protein determines its unique shape and function.

Amino Acids Have unique side groups that result in

differences in the size, shape and electrical charge of an amino acid

Nonessential amino acids, also called dispensable amino acids, are ones the body can create.

Nonessential amino acids include alanine, arginine, asparagines, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine.

Amino Acids Essential amino acids, also called

indispensable amino acids, must be supplied by the foods people consume.

Essential amino acids include histidine, isoleucine, leucine, lysine, methionine, phenyalanine, threonine, tryptophan, and valine.

Conditionally essential amino acids refer to amino acids that are normally nonessential but essential under certain conditions.

A m in o A c id R e q u ir e m e n t s o f H u m a n s - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N u t r i t io n a l ly E s s e n t ia l N u t r i t io n a l ly N o n e s s e n t ia l - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

A r g in in e a A la n i n e H is t id i n e A s p a r a g i n e I s o le u c in e A s p a r ta te L e u c in e C y s te i n e L y s i n e G lu ta m a te M e th io n in e G lu ta m i n e P h e n y la la n i n e G l y c i n e T h r e o n in e P r o l in e T r y p to p h a n S e r in e V a l in e T y r o s in e

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - a “ N u tr i t io n a l l y s e m ie s s e n t ia l .” S y n t h e s iz e d a t r a te s in a d e q u a te to s u p p o r t g r o w t h o f c h i ld r e n .

What is protein Proteins

Amino acid chains are linked by peptide bonds in condensation reactions.

Dipeptides have two amino acids bonded together.

Tripeptides have three amino acids bonded together.

Polypeptides have more than two amino acids bonded together.

Amino acid sequences are all different, which allows for a wide variety of possible sequences.

M. Zaharna Clini. Chem. 2009

Peptide bond

The Chemist’s View of Proteins Proteins

Protein Shapes Hydrophilic side groups are attracted to

water. Hydrophobic side groups repel water. Coiled and twisted chains help to provide

stability.

M. Zaharna Clini. Chem. 2009

Classification of protein Proteins are polymers of amino acids

produced by living cells in all forms of life. A large number of proteins exist with

diverse functions, sizes, shapes and structures but each is composed of essential and non-essential amino acids in varying numbers and sequences.

The number of distinct proteins within one cell is estimated at 3,000 - 5,000 The most abundant organic molecule in cells

(50-70% of cell dry weight)

M. Zaharna Clini. Chem. 2009

Size A typical protein contains 200-300

amino acids, but some are much smaller and some are much larger

Proteins range in molecular weight from 6,000 Daltons (insulin) to millions of Daltons (structural proteins)

M. Zaharna Clini. Chem. 2009

Protein Structure Primary structure –

sequence of AA In order to function properly,

proteins must have the correct sequence of amino acids.

e.g when valine is substituted for glutamic acid in the chain of HbA, HbS is formed, which results in sickle-cell anemia.

M. Zaharna Clini. Chem. 2009

Secondary structure Initial helical

folding Beta pleated sheet Held together by

Hydrogen bonding

M. Zaharna Clini. Chem. 2009

Tertiary Structure Chain folds back on

itself to form 3D structure

Interaction of R groups Responsible for

biologic activity of molecule

M. Zaharna Clini. Chem. 2009

Quaternary structure 2 or more polypeptide

chains binding together eg. Hemoglobin

Hemoglobin has 4 subunits

Two chains Two chains

Many enzymes have quaternary structures

M. Zaharna Clini. Chem. 2009

Classification by Protein Structure

Simple Proteins (contain only amino acids) are classified by shape as – Globular proteins: compact, tightly

folded and coiled chains Majority of serum proteins are globular

Fibrous proteins: elongated, high viscosity (hair, collagen)

M. Zaharna Clini. Chem. 2009

Classification by Protein Structure

Conjugated proteins contain non-amino acid groups

Amino acid portion is called apoprotein and non-amino acid portion is called the prosthetic group

It is the prothetic groups that define the characteristics of these proteins.

Name of the conjugated protein is derived from the prosthetic group

M. Zaharna Clini. Chem. 2009

Conjugated Proteins

Classification Prosthetic group

Example

Lipoprotein Lipid HDL

Glycoprotein Carbohydrates Immunoglo-bulins

Phosphoprotein Phosphate Casein of milk

M. Zaharna Clini. Chem. 2009

Functions of proteins Generally speaking, proteins do everything in the

living cells Functional classification of plasma proteins is useful

in understanding the changes that occur in disease: Tissue nutrition Proteins of immune defense

Antibodies Acute phase proteins

Proteins associated with inflammation Transport proteins( albumin, transferrin)

Proteins used to bind and transport Hemostasis

Proteins involved in forming clots and acting very closely with complement

M. Zaharna Clini. Chem. 2009

Functions of proteins Regulatory

( receptors, hormones ) Catalysis,

enzymes Osmotic force

Maintenance of water distribution between cells and tissue and the vascular system of the body

Acid-base balance Participation as buffers to maintain pH

Structural, contractile, fibrous and keratinous

Monogastric Protein Digestion Whole proteins are not absorbed

Too large to pass through cell membranes intact

Digestive enzymes Hydrolyze peptide bonds

Secreted as inactive pre-enzymes Prevents self-digestion

H3N+ C

HC

R

O

NH

CH

CO

RNH

CH

C

R

O

O–

Monogastric Protein Digestion Initiated in stomach

HCl from parietal cells Stomach pH 1.6 to 3.2 Denatures 40, 30, and 20 structures

Pepsinogen from chief cells

Cleaves at phenylalanine, tyrosine, tryptophan

Protein leaves stomach as mix of insoluble protein, soluble protein, peptides and amino acids

Aromatic amino acids

Pepsinogen

HClPepsin

Protein Digestion – Small Intestine

Pancreatic enzymes secreted Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase Collagenase

Zymogens

Monogastric Digestion – Small Intestine

Zymogens must be converted to active form Trypsinogen Trypsin

Endopeptidase Cleaves on carbonyl side of Lys & Arg

Chymotrypsinogen Chymotrypsin Endopeptidase

Cleaves carboxy terminal Phe, Tyr and Trp

Procarboxypeptidase Carboxypeptidase

Exopeptidase Removes carboxy terminal residues

Enteropeptidase/Trypsin

Trypsin

Trypsin

Protein Digestion Small intestine (brush border)

Aminopeptidases Cleave at N-terminal AA

Dipeptidases Cleave dipeptides

Enterokinase (or enteropeptidase) Trypsinogen trypsin Trypsin then activates all the other enzymes

Trypsin Inhibitors Small proteins or peptides Present in plants, organs, and

fluids Soybeans, peas, beans, wheat Pancreas, colostrum

Block digestion of specific proteins Inactivated by heat

Protein Digestion Proteins are broken down to

Tripeptides Dipeptides Free amino acids

Free Amino Acid Absorption

Free amino acids Carrier systems

Neutral AA Basic AA Acidic AA Imino acids

Entrance of some AA is via active transport

Requires energy

Na+ Na+

Peptide Absorption

Form in which the majority of protein is absorbed

More rapid than absorption of free amino acids

Active transport Energy required

Metabolized into free amino acids in enterocyte

Only free amino acids absorbed into blood

Absorption of Intact Proteins Newborns

First 24 hours after birth Immunoglobulins

Passive immunity Adults

Para cellular routes Tight junctions between cells

Intracellular routes Endocytosis Pinocytosis

Of little nutritional significance... Affects health (allergies and passive immunity)

Protein Transport in the Blood

Amino acids diffuse across the basolateral membrane Enterocytes portal blood liver

tissues Transported mostly as free amino acids

Liver Breakdown of amino acids Synthesis of non-essential amino acids

Groff & Gropper, 2000

Overview of Protein Digestion and Absorption in Monogastrics

OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT ORGANISM

Ingested protein

Bio- synthesis Protein

AMINO ACIDS

Nitrogen Carbon

skeletons

Urea

Degradation (required)

1 2 3

a

b

PurinesPyrimidinesPorphyrins

c c

Used for energy

pyruvateα-ketoglutaratesuccinyl-CoAfumarateoxaloacetate

acetoacetateacetyl CoA

(glucogenic)

(ketogenic)

Amino Acid Catabolism Deamination of Amino Acids removal of the a-amino acids

Oxidative DeaminationNon-oxidative DeaminationTransamination

TRANSAMINATION

The term amphibolic is used to describe a biochemical pathway that involves both catabolism and anabolism

Reductive amination catalyzed byglutamate dehydrogenase (this is physiological

important becouse high conc. Of NH4 ion are cytotoxic)

Glutamine synthesis is coupled to hydrolysis of ATP

Pyruvate is an amphibolic intermediatein synthesis of alanine

Glutamte dehydrogenase, glutamine synthetase and aminotranferases play central roles in amino acid biostynthsis

The combined action of the above said enzymes converts inorganic ammonium ion in to the α-amino nitrogen of AA

Asparagine synthesis is energetically

favorable due to coupling to ATP hydrolysis

Serine biosynthesis(oxidation of the α-hydroxyl group of the glycolytic intermidiate 3-phosphoglycerate by 3-phosphoglycerate dehygrogenase convert it to 3-phosphohydroxypuruvate.

Transamination and subsequent dephosphorylation is strongly favored)

Multistep pathway for glycine biosynthesis

Glycine is also synthesized from serine

Cysteine is not nutritionally essential, however it is derived from methionine

+NH3

CH

C

H2C

O-

O

H2C S CH3

Tyrosine is formedfrom phenylalanine

Hydroxyproline is formed after protein synthesis

Selenocysteine is synthesized from serine and selenophosphate

Amino acids that are synthesized de novo in humans. All are related by a small number of steps to glycolysis or TCA cycle intermediates.

Salvage pathways for formation of certain nonessential amino acids from other amino acids

Amino Acid formed Precursor Amino Acid

Arginine Proline

Cysteine Methionine

Tyrosine Phenylalanine

NITROGEN BALANCE

Nitrogen balance = nitrogen ingested - nitrogen excreted

(primarily as protein) (primarily as urea)

Nitrogen balance = 0 (nitrogen equilibrium)

protein synthesis = protein degradation

Positive nitrogen balance

protein synthesis > protein degradation

Negative nitrogen balance

protein synthesis < protein degradation

UREA CYCLE

mitochondria

cytosol

Function: detoxification of ammonia (prevents hyperammonemia)

FATE OF THE CARBON SKELETONS

Carbon skeletons are used for energy.

Glucogenic: TCA cycle intermediates(gluconeogensis)

Ketogenic: acetyl CoA, acetoacetyl CoA, or acetoacetate

Protein synthesis On-going, semicontinuous activity

in all cells but rate varies greatly between tissues

Rate of protein synthesis

Ks (%/d)

Tissue Pig Steer

LiverGutMuscle

23455

21392

Ks = fraction of tissue protein synthesized per day

Protein synthesis On-going, semicontinuous activity in all

cells but rate varies greatly between tissues

Rate is regulated by hormones and supply of amino acids and energy

Energetically expensive requires about 5 ATP per one peptide bond

Accounts for about 20% of whole-body energy expenditure

Protein degradation Also controlled by hormones and

energy status Method to assist in metabolic

control turns off enzymes

Protein synthesis and degradation Synthesis must exceed

degradation for net protein deposition or secretion

Changes in deposition can be achieved by different combinations of changes in synthesis and degradation

Changes in deposition

Synthesis Degradation Deposition

No change

No change

No change

Protein synthesis and degradation Synthesis must exceed degradation

for net protein deposition or secretion Changes in deposition can be

achieved by different combinations of changes in synthesis and degradation

Allows for fine control of protein deposition

Proline biosynthesis(the initial reaction of proline biosynthsis converts the ᵞ-carboxyl group of glutamate to the mixed acid anhydride of glutamate ᵞ-phospate. Subsequent reduction form glutamate ᵞ- semialdehyde,, which following spontaneously cyclization is reduced to L-Proline )

Protein synthesis and degradation Other possible reasons for

evolution of protein turnover include Allows post-translational conversion

of inactive peptides to active forms (e.g., pepsinogen to pepsin)

Minimizes possible negative consequences of translation errors

Protein catabolism Some net catabolism of body

proteins occurs at all times Expressed as urinary nitrogen

excretion yields urea

Minimal nitrogen excretion is termed endogenous urinary nitrogen (EUN)

Urinary nitrogen excretion

Urine

KIDNEY

LIVER

Urea

Urea

CO2

Amino acids keto acids

NH3

Blood

Protein Synthesis

Protein Synthesis Synthesis= the process of building

or making DNA= (deoxyribonucleic acid) the

genetic code or instructions for the cell

RNA= ribonucleic acid Amino Acids= building blocks of

proteins

DNA RNA

Deoxyribonucleic Acid Ribonucleic Acid

Sugar=deoxyribose Sugar= ribose

Contains 1 more H atom than deoxyribose

Double stranded Single stranded- a single strand of nucleotides

Nitrogen bases: ATCG Nitrogen bases: AUCG

U=Uracil

http://www.princeton.edu/%7Ehos/images/rna.gif

http://images2.clinicaltools.com/images/gene/dna_versus_rna_reversed.jpg

STEP 1: TRANSCRIPTION= making RNALocation: Eukaryotes-nucleusProkaryotes-cytoplasm

1. RNA polymerase binds to the gene’s promoter

2. The two DNA strands unwind and separate.

3. Complementary nucleotides are added using the base pairing rules EXCEPT:

A=U The rest are the same C=G, T=A, G=C

Try this example. Using the following DNA sequence,

what would be the complementary RNA sequence?

ATCCGTAATTATGGC UAGGCAUUAAUACCG

http://www.odec.ca/projects/2004/mcgo4s0/public_html/t3/mRNA%20to%20protein.gif

1. Messenger RNA= mRNA is a form of RNA that carries the instructions for making the protein from a gene and delivers it to the site of translation.

Codon= three nucleotide sequence Transfer RNA= tRNA single strands of

RNA that temporarily carry a specific amino acid on one end and has an anticodon

Anticodon-a 3 nucleotide sequence that is complementary to an mRNA codon

Ribosomal RNA= rRNA- a part of the structure of ribosomes

Codon and Anticodon Codon-found on mRNA Anticodon-found on

tRNA

http://images.google.com/imgres?imgurl=http://www.obgynacademy.com/basicsciences/fetology/genetics/images/codon_GCA.gif&imgrefurl=http://www.obgynacademy.com/basicsciences/fetology/genetics/&usg=__4MvAO2N3sXbERXQwODVDSqtsOjM=&h=160&w=168&sz=4&hl=en&start=5&tbnid=toyuIN8drVBr4M:&tbnh=94&tbnw=99&prev=/images%3Fq%3Dcodon%26gbv%3D2%26hl%3Den

http://www.microbelibrary.org/microbelibrary/files/ccImages/Articleimages/kaiser/tRNA_arg.jpg

STEP 2-TRANSLATION- Assembling proteins- in the cytoplasm mRNA leaves nucleus and enters cytoplasm tRNA molecules with the complementary

anticodon and a specific amino acid arrives at the ribosome where the mRNA is waiting.

Peptide bond forms between amino acids tRNA molecule leaves and a new one comes

with another amino acid. Amino acids continue to attach together until

the stop codon and a protein is formed

SUMMARY Transcription= process of making

RNA from DNA Translation= RNA directions are

used to make a protein from amino acids

• DNARNA Protein Transcription Translation

nucleus Cytoplasm on ribosome

DNA RNA

Deoxyribonucleic Acid Ribonucleic Acid

Sugar=deoxyribose Sugar= ribose

Contains 1 more H atom than deoxyribose

Double stranded Single stranded- a single strand of nucleotides

Nitrogen bases: ATCG Nitrogen bases: AUCG

U=Uracil

Video Clips http://www.youtube.com/watch?v=

KvYEqGb7XN8&feature=related http://www.youtube.com/watch?v=

B6O6uRb1D38&feature=related

DNA Replication RNA Transcription

DNA polymerase is used. RNA polymerase is used.

DNA nucleotides are linked.

RNA nucleotides are linked.

A DNA molecule is made.

An RNA molecule is made.

Both DNA strands serve as templates.

Only one part of one strand of DNA ( a gene) is used as a template.

Explain the steps in protein synthesis.

http://stemcells.nih.gov/info/scireport/images/figurea6.jpg

Ruminant Protein Digestion

Ruminants can exist with limited dietary protein sources due to microbial protein synthesis Essential amino acids synthesized

Microbial protein is not sufficient during: Rapid growth High production

Protein in the Ruminant Diet Types of protein:

Dietary protein – contains amino acids Rumen Degradable Protein (RDP) – available for

use by rumen microbes Rumen Undegradable Protein (RUP) – escapes

rumen fermentation; enters small intestine unaltered

Varies with diet, feed processing Dietary non-protein nitrogen (NPN) – not

true protein; provides a source of nitrogen for microbial protein synthesis

Relatively CHEAP - decreases cost of protein supplementation

Ruminant Protein Feeding Feed the rumen microbes first (RDP)

Two counteractive processes in rumen Degradation of (dietary) protein Synthesis of microbial protein

Feed proteins that will escape fermentation to meet remainder of animal’s protein requirements

Escape protein, bypass protein, or rumen undegradable protein (RUP)

Aldehydes increase inter-protein cross-linking Heat treatment

Utilization depends on Digestibility of RUP source in the small intestine Protein quality

Protein Degradation in RumenFeedstuff % Degraded

in 2 hours

Urea 100

Alfalfa (fresh) 90

Wheat Grain 78

Soybean Meal 65

Corn Grain 48

Blood Meal 18

Rumen Protein Utilization Factors affecting ruminal degradation

Rate of passage Rate of passage degradation

Solubility in water Must be solubilized prior to degradation

Heat treatment Degradation

N (and S) availability Energy availability (carbohydrates)

Protein Fractions Dietary proteins classified based on

solubility in the rumen A

NPN, instantly solubilized/degraded B1 B2 B3

Potentially degradable C

Insoluble, recovered in ADF, undegradable

Ruminant Protein Digestion

Rumen microbes use dietary protein Creates difference between protein quality in

feed and protein actually absorbed by host Microbes break down dietary protein to

Amino acids NH3, VFAs, and CO2

Microbes re-synthesize amino acids Including all the essential amino acids from NH3 and

carbon skeletons

No absorption of protein or amino acids from rumen (or from cecum or large intestine!)

Protein Hydrolysis by Rumen Microbes Process with multiple steps

Insoluble protein is solubilized when possible Peptide bonds of solubilized protein are cleaved

Microbial endo- and exo-peptidases Amino acids and peptides released

Peptides and amino acids absorbed rapidly by bacteria

Bacteria degrade into ammonia N (NH3) NH3 used to produce microbial crude protein (MCP)

Microbial Crude Protein (MCP) Protein produced by microbial

synthesis in the rumen Primary source of protein to the

ruminant animal Microbes combine ammonia nitrogen

and carbohydrate carbon skeleton to make microbial crude protein

Diet affects the amount of nitrogen entering the small intestine as microbial crude protein

Factors Limiting Microbial Protein Synthesis Amount of energy

ATP Available nitrogen

NPN Degraded feed intake protein nitrogen (RDP)

Available carbohydrates Carbon residues for backbone of new amino acid

Microbial crude protein synthesis relies on synchronization of carbohydrate (for carbon backbones) and nitrogen availability (for amino group)

Microbial Protein Synthesis Synchronization of carbohydrate and N availability

NPN supplementation Carbohydrates used for carbon skeleton of amino acids

VFA (CHO fermentation)

Rumen NH3

Blood NH3

Adapted from Van Soest, 1994

Time post-feeding

Con

cent

ratio

n

Carbon backbone(from CHO fermentation)

Microbial Protein Formation

Dietary NPN

Dietary Soluble RDP

Microbial ProteinsAmino

Acids

Carbon Skeletons

Sulfur

Other Co-factors

NH3 ATP

Dietary Starch Sugar

Dietary Cellulose Hemicellulose

rapid

slow

rapid

slower

Dietary Insoluble RDP

very slow

Nitrogen Recycling Excess NH3 is absorbed

through the rumen wall to the blood Quickly converted to urea in the liver

Excess NH3 may elevate blood pH Ammonia toxicity Costs energy Urea (two ammonia molecules linked together)

Relatively non-toxic Excreted in urine Returned to rumen via saliva (rumination important)

Efficiency of nitrogen recycling decreases with increasing nitrogen intake

Nitrogen Recycling Nitrogen is continually recycled to

rumen for reutilization Ability to survive on low nitrogen diets Up to 90% of plasma urea CAN be recycled

to rumen on low protein diet Over 75% of plasma urea will be excreted

on high protein diet Plasma urea enters rumen

Saliva Diffuses through rumen wall from blood

Urea

Ammonia + CO2

Urease

Feed Protein, NPN and CHO

Feed Protein

Feed NPN

NH3/NH4

Bacterial N

NH4+ loss

MCP

RDP

RUPFeed Protein

AA

MCP

AA

NH3

Liver

Blood Urea

Salivary N

ATP

RUMEN

SMALL INTESTINE

Ruminant Digestion and Absorption

Post-ruminal digestion and absorption closely resembles the processes of monogastric animals However, amino acid profile entering

small intestine different from dietary profile

Overview of Protein Feeding Issues in Ruminants

Rumen degradable protein (RDP) Low protein quality in feed very good

quality microbial proteins Great protein quality in feed very good

quality microbial proteins Feed the cheapest RDP source that is

practical regardless of quality Rumen undegradable protein (RUP)

Not modified in rumen, so should be higher quality protein as fed to animal

May cost more initially, but may be worth cost if performance boosted enough

Salivary Urea

NPN

NH3

POOL

Dietary Nitrogen Non-utili

zed Ammonia

NH3 UREA

LIVER

LEVEL TOPROVIDE FORMAXIMUMMICROBIAL GROWTH

MICROBIAL PROTEIN

65% OF PROTEIN

35% OF PROTEIN

SMALL INTESTINE

AMINO ACIDS

AMINO ACIDSPROTEIN

AMINO ACIDS

PEPTIDES

Reticulo-rumen

RUP

RDP

Recycled urea

Functional Feeds

Functional feeds may be defined as any feed or feed ingredient that produces a biological effect or health benefit that is above and beyond the nutritive value of that feedstuff

Many feeds and their components fit this definition

Functional Proteins

Functional proteins are feed-derived proteins that, in addition to their nutritional value, produce a biological effect in the body

Feedstuffs with Biologically Active Proteins Milk Colostrum Whey Protein Concentrates/Isolates Plasma or serum Other animal-derived feedstuffs

Fish meal Meat and bone meal

Fermented animal-based products Yeast Lactobacillus organisms

Soy products

Protein Size Affects Function Many protein hormones are functional even

when fed to animals thyrotropin-releasing hormone (TRH, a 3-amino acid

peptide) luteinizing hormone-releasing hormone (LHRH, a 10-

amino acid peptide) insulin (a 51-amino acid polypeptide)

The smaller the peptide, the more “functional” it is when fed

100% activity for TRH, 50% for LHRH, and 30% for insulin Feedstuffs containing protein hormones

(colostrum) have biological activity when fed to animals

Production of Bioactive Peptides From Biologically-Inactive Proteins Peptides produced from intact inactive

proteins by incomplete digestion via proteases in stomach and duodenum or via microbial proteases in rumen

Many of these biologically active peptides (typically 2-4 amino acid residues) are stable from further digestion Some peptides bind to specific epithelial

receptors in intestinal lumen and induce physiological reactions

Some peptides are absorbed intact by a specific peptide transporter system into the circulatory system and transported to target organs

Responses to Feeding Functional Proteins or Peptides

Antimicrobial – including control of gut microflora Antiviral Binding of enterotoxins Anti-carcinogenic Immunomodulation Anti-oxidant effects Opioid effects Enhance tissue development or function Anti-inflammatory Appetite regulation Anti-hypertensive Anti-thrombic

Functional Activity of Major Milk Proteins Caseins (α, β and κ)

Transport of minerals and trace elements (Ca, PO4, Fe, Zn, Cu), precursor of bioactive peptides, immunomodulation (hydrolysates/peptides)

β-Lactoglobulin Retinol carrier, binding fatty acids, potential antioxidant, precursor for

bioactive peptides α-Lactalbumin

Lactose synthesis in mammary gland, Ca carrier, immunomodulation, anticarcinogenic, precursor for bioactive peptides

Immunoglobulins Specific immune protection (antibodies and complement system), G, M, A

potential precursor for bioactive peptides Glycomacropeptide

Antiviral, antithrombotic, bifidogenic, gastric regulation Lactoferrin

Antimicrobial, antioxidative, anticarcinogenic, anti-inflammatory, immunomodulation, iron transport, cell growth regulation, precursor for bioactive peptides

Lactoperoxidase Antimicrobial, synergistic effect with Igs and LF

Lysozyme Antimicrobial, synergistic effect with Igs and LF

Serum albumin Precursor for bioactive peptides

Proteose peptones Potential mineral carrier

Functional Activity of Minor Milk Proteins

Growth factors (IgF, TGF, EGF) stimulation of cell proliferation and differentation

Cytokines regulation of immune system (interferons,

interleukins, TGFβ, TNFα) Inflammation Increases immune response

Milk basic protein (MBP) Promotion of bone formation and suppression of

bone resorption Osteopontin

Modulation of trophoblastic cell migration

Protein Fragments That Have Biological Activity

Functional Protein Effects During Toxin or Disease Challenge

During intestinal inflammation, some functional proteins:

Reduce local inflammatory response excessive activation of inflammatory cells permeability

Increase Nutrient absorption Barrier function Intestinal health

During intestinal inflammation, some functional proteins:

Are absorbed and create adverse allergenic and immune responses in the body

Modified from Campbell, 2007