29 Protein Digestion, Absorption And Metabolism

Front 1

Where does protein digestion take place in monogastrics?

Back 1

Oral cavity

Stomach (corpus&fundus)

Duodenum

Jejunum & Ileum

Front 2

What happens to protein in the mouth?

Back 2

Mechanical breakdown - no proteolytic digestion!!!

Front 3

What happens in the corpus and fundus?

Back 3

HCL (from parietal cells) hydrolyzes some bonds and activates pepsinogen (from chief cells) to PEPSIN!

Front 4

What happens in the duodenum?

Back 4

Enterokinase activates trypsin which in turn activates other zymogens

Front 5

What happens in the jejunum and ileum?

Back 5

Absorption of di/tripeptides and AA

Front 6

Intestinal peptide absorption - pancreatic (luminal) phase...

Back 6

1. Peptides reach intestine

2. Hormones (CCK or Secretin) are sensed and activate the release of ex/endo-peptidases

3. Peptides -> di/tripeptides and AA

Front 7

Intestinal peptide absorption - mucosal phase...

Back 7

1. Short Peptides are transported by PepT1 on epithelial membrane inside cell then into the blood (portal vein) to liver

2. AA diffuse through epithelial membrane to blood to liver via portal vein

Front 8

Explain the pancreatic phase in greater detail...

Back 8

1. Proteins are digested by ex/endopeptidases (pepsin) to oligo-peptides

2. Oligo-peptides are digested by enterokinase-trypsin and oligo peptidases to di/tripeptides

3. Some di/tripeptides are digested to AA by exo-peptidases present on the brush boarder

Front 9

Explain the mucosal phase in greater detail...

Back 9

1.Di/tripeptides carried into cell via PepT1 OR cell penetrating peptide OR paracellular

2. AA are carried by AA carrier then into blood

3. Peptide in the cells can go though metabolism (catabolism or synthesis) and AA are exported to blood via diffusion

4. Peptide in the cells can travel straight to blood via diffusion

Front 10

During absorption of protein, what happens in baby calves?

Back 10

-Dont have the capacity to digest proteins (zymogens not activated) so that Ig are protected from digestion

-Protein (colostrum) is transported via pinocytosis to lymph

Front 11

Where does PepT1 get the H+ from to power peptide transport?

Back 11

-H+ is from an Na+/H+ antiporter

-Na+ concentration is kept low via ATPase on basal membrane

Front 12

What is an inhibitors of protein digestion?

Back 12

-Raw soybeans have trypsin inhibitors = decrease protein digestibility and growth (heat inactivates)

Front 13

Example of an oligopeptide transporter (major tissue and substrates)

Back 13

PEPT1: intestine, kidney (lysosomes)

Substrates: Di and Tri peptides, protons

Front 14

What happens in the luminal phase of protein digestion?

Back 14

Large proteins broken down to oligopeptides by enzymes in stomach and intestines

1. Endopeptidases (pepsin, rennin, trypsin, chymotrypsin, elastase) cleave in middle to generate small peptides

2. Exopeptidases (carbopeptidases A&B) release AA from ends

Front 15

What happens in the membranous phase of protein digestion?

Back 15

Peptidases on brush border surface hydrolyze luminal phase end-products to AA which are absorbed

Front 16

When peptides are in the epithelial cell, metabolism take place. What are the end products of the Synthesis or catabolism?

Back 16

Synthesis: Proteins-hormones, enzymes, non essential AA

Catabolism: glutamine

Front 17

What are the 2 of the 4 classifications of AA that we have to know?

Back 17

1. Nutritional value

2. Metabolic Fate

Front 18

What are the nutritional AA classes?

Back 18

1. Essential: (PVT TIM HALL) Phe, his, Ile, leu, lys, met, thr, val, arg (birds/carnivores), trp

2.Non essential: Gln, Gly, Asp, Pro, Ala, Ser, Cys, Tyr, Selenocysteine

Front 19

What are the AA classes of metabolic fate?

Back 19

1. Glucogenic - Gly, Ala, Val, Ile, Phe, Trp, Met, Pro, Ser, Thr, Tyr, Asp, Cys, Gln, Asp, Glu, His, Arg

2. Ketogenic - LYS, LEU

3. Glucogenic and Ketogenic - Phe, Tyr, Trp, Thr, Ile

Front 20

Interorgan AA exchange occurs between what organs?

Back 20

-Gut -> liver, muscle

-Muscle -> brain

-Liver -> muscle, kidney

-Brain -> liver, kidney, gut (glutamine)

Front 21

Interorgan AA exchange from gut...

Back 21

1. AA travel via portal vein

2. Glucose diffusion

Front 22

Interorgan AA exchange liver...

Back 22

-Aromatic AA (Phe, Tyr, Trp catabolism) are metabolized for energy (gluconeogenesis and oxidation) and biosynthesis -> glucose and urea

-urea goes to kidney

-Branched Chain AA (Ile, Leu, Lys, Val) are passed into systemic circulation to be metabolized in muscle

Front 23

Interorgan AA exchange in Muscle...

Back 23

-BCAA metabolized via BCAA transaminase -> products sent to brain (valine), gut (energy), and circulation (glutamine)

Front 24

Interorgan AA Exchange in Brain...

Back 24

-Valine from muscle feeds brain to create glutamine

-Glutamine (Glu) goes to intestinal cells = Glu&Asn for energy to release Ala+CO2+NH4+Citrulline

-Glutamine foes to kidney for GLUCONEOGENEISIS

Front 25

Interorgan AA exchange in Kidney...

Back 25

-Takes up Glutamine (gluconeogenesis) -> glucose or NH4

-Urea -> urea or uric acid (birds)

Front 26

Overview of N metabolism.... AA biosynthesis..

Back 26

Front 27

Protein synthesis...what does it form?

Back 27

Free AA from N metabolism and the diet (1%)

-Some go to lipids, glucose, CO2+H2O, NH3, Urea, (minor)

-Majority go to form Protein bound AA (99%) in the skin, heart, skeletal muscle, intestine and liver (insulin, IGF-1, growth hormone, glucose, ketones, BBCA, etc.)

Front 28

Protein degradation... what does it form?

Back 28

-Protein bound AA are broken down to free AA of a-AA pool

(Glucagaon, glucocorticoids, hyperthyroidism, cytokines, etc.)

Front 29

What are the two way to metabolize N?

Back 29

1. Glutamate dehydrogenase reaction

2. Transamination

Front 30

Glutamate dehydrogenase reaction...

Back 30

-Key to fixing/removing NH3-N to/from a-amino groups

-Higher animals -deficient in a-KG because..

-limited ability to carry out this step

- need dietary a-amino groups

-cannot efficiently deal with excess NH3 (hepatic/renal failure)

Front 31

Transamination...

What is this common to?

Back 31

-Critical reaction for metabolic (N) economy

-Equilibrium reaction (depending on concentration) AA can be deaminated or keto-acids aminated

-liver/renal failure must give dietary supplementation of keto-acids to mop up excess amino groups

Common to: a-KG to glutamate, pyruvate to alanine, oxaloacetate to aspartate

Front 32

Protein digestion in Ruminants what happens to true protein?

Back 32

True protein (AA) go to RUP or RDP

-RUP becomes metabolizable protein in intestines

-RDP is digested to AA -> CO2+ VFA's or -> portal vien to liver and converted to urea

or microbial protein

Front 33

Protein digestion in Ruminants what happens to VFA?

Back 33

-used for energy by microbial protein

Front 34

Protein digestion in Ruminants what happens to NPN?

Back 34

-converted to NH3 by urease which is then used for microbial protein or transported via portal vein to liver

Front 35

Protein digestion in Ruminants what happens to urea?

Back 35

Urea (NH3) is transported to the liver then..

1. Transported to kidney for excretion

2. Recycled into saliva

3. recycled into NPN in rumen

Front 36

What proportion of protein flow is microbial protein?

Back 36

-45-60%

Front 37

What does metabolizable protein consist of?

Back 37

-microbial protein

-RUP

-Endogenous protein (20%)

Front 38

How is microbial protein made?

Back 38

1. peptides that have been released from dietary protein and AA are incorporated into microbial protein

2. Ammonia and VFA's to make AA and then the AA are incorporated into protein

3. VFA's can be used for energy OR are excreted for host use

Front 39

How is urea made in the liver?

Back 39

-Begins in the mitochondria (NH4)

- Ornithine is converted to citruline with the addition of carbamoyl phosphate (omithine transcarbomylase)

-Citruline -> Argino succinate with addition of aspartate and ATP (out of mitochondria)

-Arginio succinate to arginine (argininosuccinase)

-**Arginase is converted to ornithine and UREA is a byproduct (via arginase)

Front 40

Why do we feed urea to cattle and what is the upper limit?

Back 40

1. Inexpensive N2 source for replacing protein

2. Upper limit 1% of diet DM

Front 41

What happens when you feed urea and low quality forages?

Back 41

-Imbalances between the rate of ammonia available and the amount of carbon (from fiber digestion)

-microbes can't produce microbial protein

-AMMONIA abosorbed into the blood stream (TOXIC)

Front 42

What are the clinical signs of urea toxicity (NH3)?

Back 42

1. Appear 20-30minutes after

2. Rapid and laboured breathing

3. Tremors, incoordination, inability to stand

-tetany

Front 43

What are the mechanisms of urea toxicity?

Back 43

1. increase in rumen [NH3] = increased rumen pH (alkaline)

2. pH increases then a shift from NH4 to NH3

3. NH3 absorbed faster

4. Liver capacity to convert NH3 to urea is excreted

5. NH3 accumulation in blood - 2mg NH3/100mL plasma is toxic

Front 44

How do you treat?

Back 44

1) Oral drench with 5% acetic acid (shifts equilibrium NH3 → NH4+)

2) Cold water drench (↓ urea hydrolysis + dilutes NH3)

3) Rapid rumen evacuation

Front 45

What are the similarities between ruminants and non?

Back 45

1. Metabolic pathways are similar

2. Synthesize non essential AA

3. Cant synthesize essential AA

4. Proteins undergoing turnover

5. AA limited storage

Front 46

Ruminant nutrition is generally not concerned with AA composition of dietary protein - why?

Back 46

-because type of feed has minimal effect on AA comp of bacteria and protozoa leaving the rumen

Front 47

Are ruminants efficient in converting dietary protein to milk and meat?

Back 47

No! (70-75% N2 intake is excreted in urine and feces)

Front 48

Describe urea recycling?

What is the rate limiting enzyme?

Back 48

RATE LIMITING = ARGINASE

1. urea synthesis from NH3 or deamination of AA in liver

2. Urea excreted in urine or recycled through saliva or rumen wall (Urea Transporter)

3. Ruminal bacteria have a high capacity to hydrolyze urea

Front 49

Ruminal protein degradation in ruminants...

Back 49

1. microbes cleave peptide bonds to release AA

2. AA deaminated by microbes, releasing NH3 and keto acids (C skeleton)

3. Protein leaves rumen (microbial, bypass, and secretions)

Front 50

Describe microbial protein synthesis...

Back 50

Microbes use NH3 (from NPN), keto acids and energy to synthesize AA. (must have fermentable feed and NH3)

Front 51

Describe microbial protein turnover...

Back 51

Microbes are lysed by lysosome in abomasum = release microbial protein that is then digested by proteases