Amino Acids And Protein Metabolism

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					Amino Acids And Protein Metabolism

Rudimentary Info


Amino Acids




Carbon skeletons with an amine group attached. Building blocks of peptides and proteins.

Rudimentary Info


Ketoacids




Carbon skeletons without an amine group. These can enter various metabolic pathways.

More Basics


Transamination




The transfer of an NH3 group from one molecule to another. Can occur in most tissues, but mostly in the liver.

A Defining Moment
 

Anaplerosis – adding to a pathway Catapleurosis – taking from a pathway

Are You The Keymaster?
 

Three key converstions: Amino Acid Α-ketoacid
  

Alanine Glutamate Aspartate

Pyruvate α-ketogluterate Oxaloacetate

 Aminotransferase


is the key!

Alanine Aminotransferase  Aspartate Aminotransferase

Classification




Like fats, some AAs must be consumed while others can be made. This extends the essential and non-essential classification to AAs.

Sorry, You’re Not on the List.


Non-Essential



  


 


  

Alanine Asparagine Aspartate Arginine Cysteine Glutamate Glutamine Glycine Histidine Proline Serine Tyrosine



Essential
  

  
 

Methionine Threonine Valine Isoleucine Leucine Lysine Phenylalanine Tryptophan

More Labeling


Some amino acids are glucogenic.


Can be made into glucose. Made into ketones. Made into glucose or ketones depending on metabolic need.



Others are ketogenic.




Some are both.


What about N?


Nitrogen
 

Can’t be stored. Must be excreted.


How much and when?



Nitrogen Balance


Measure of protein intake.

Protein in = Protein out

Nitrogen Balance


Positive or Negative






Positive: More protein consumed than used. Negative: More protein used than consumed. Positive N-balance is optimal because it tells us that lean mass is not being broken down to satisfy the bodies need for AA.

Positive Nitrogen


Statistics
   

In=Out: .57g protein/kg body wt RDA: .8 to 1.0g protein/kg body wt Endurance: 1.2 to 2.0g protein/kg body wt Resistance: >2.0g protein/kg body wt

USDA Grade A


Protein Quality


Dependant on several factors.


Completeness, digestibility, absorption, utilization, etc.

You Complete Me!


Complete proteins
 

Contain all essential AAs. Animal origin. Missing some essential AAs. Plant origin. Requires complimentary foods to be complete.



Incomplete proteins
  

Protein Score.




Protein sources are compared to a known complete protein source and graded on their completeness. Eggs are the reference.

Can You Stomach This?


The body has different abilities to digest different protein sources.
 

Animal sources: 90-99% digestible. Plant sources: 70-90% digestible.



This digestibility percentage is used to correct the completeness score.


Protein digestibility corrected AA score. (PDCAAS)

Protein Efficiency.


Measured by comparing protein consumption with weight gain.


Higher weight gain = higher efficiency.

Worth Its Weight in Gold!


Biological Value.




Measures absorption of protein compared to protein retained in the organism. High retention = high BV Scores can be skewed if consumption levels are above or below what is needed for nitrogen balance.



Flaw.


Protein Utilization.


Net Protein Utilization.


Compares protein retained to protein consumed.

Protein Quality Review.


Completeness Score (AA score)


Essential AA in a protein source. Uses digestibility to correct completeness score. Weight gain compared to protein consumption. Protein retained compared to protein absorbed.



PDCAAS




Protein Efficiency Ratio




Biological Value




Net Protein Utilization


Protein retained compared to protein consumed.

Eat It, Digest It, Absorb It.


Protein, Peptide, AA absorption
  

Occurs in the proximal small intestine. Sodium mediated carrier required. AA compete for carriers


Carriers have greater affinity for essential and BCAA.

Super Absorbent.


Peptide absorption in the SI occurs more readily than free AA absorption.
 

Peptide absorption = 67% Free AA absorption = 33%



The liver is the primary site for AA uptake.


50-65% of AAs absorbed here.

Liver vs. Muscle


While the liver can oxidize most of the 20 AA, muscle can only oxidize 6 AA.


Asparagine, glutamate, aspartate, Leucine, isoleucine, and valine. Remember, oxidation and metabolism are not the same. Alanine has a special job in the muscle.



Where’s alanine?




More Protein Please


Getting protein into the cells
  

Up a concentration gradient Requires ATP Requires a carrier

Protein must be pulled into the cell!

Protein

Getting Inside the Cell.


γ-glutamyl cycle
 

Used to get AA into body cells. Uses glutamate to escort AA into the cell. The intracellular source of glutamate. What other jobs does glutathione have?



Glutathione
 

AA

γ-glutamyl cycle
Membrane Protein complex

ECF

Cytosol
Glutamate AA

Glutamate Glutathione Glycine & Cystine
AA

Glutamate

The Protein Story So Far…
Protein Peptide Free AA

Small intestine

Peptide Carrier Complex

AA Carrier Complex
Free AA

Enterocyte

Blood Liver Muscle
Blood

Body tissues

Where does all this go?


Amino acids
 

Used in muscle Used for energy (alanine) Sent to various metabolic pathways Krebs, GNG, etc.
Used to excrete N



Ketoacids
 



Urea


Protein, It does a body good!


15-20% of total body mass is protein.


~12kg 100g – 200g 50% of free pool is in muscle ICF 50% in ECF & ICF of other tissues



<2% is found in the “free pool”.
  

Keto Acids.


Pyruvate
 

Gluconeogenic via Lactate. Cori Cycle. Anapleurotic for Krebs Cycle. GNG intermediate. TCA intermediate. Found in the Urea cycle.

 

α-ketogluterate


OAA
  

More To Come!

Amino Acids and GNG


Alanine


Made from pyruvate, using the NH3 of glutamate.





Gluconeogenic AA via Glucose-alanine cycle. May provide 5% of energy during exercise.

The Glycogen Conundrum.


Muscle cannot export glucose harvested from glycogen.


It lacks the enzyme Glucose-6-Phosphatase. Run glucose through Glycolysis and send the products to GNG.
Cori Cycle  Glucose-Alanine Cycle




Solution:


Glutamate and Glutamine


Glutamate


One NH3 group. Two NH3 groups.



Glutamine


Glutamine – Glutamate Cycle (GNG version) Step 1
Muscle
Amino Acid Glutamate

Liver

Glutamate Urea Blood

Glutamine Keto Acid

Glutamine

TCA GNG

Glutamine – Glutamate Cycle (GNG version) Step 2
Muscle Blood Liver

Pyruvate

Glucose

Glutamate
Glutamate

Urea

Alanine a-ketogluterate

Alanine

Krebs

Muscular Uptake


After eating, 90% of AA uptake is made up of four AAs.
 

BCAA: Leucine, Isoleucine, Valine Glutamate



With this increased intake, muscular release of Glutamine more than doubles.

Muscular Release


Most of the glutamine released by the muscle goes to the gut to aid in DNA production for cellular turnover.

Glutamine – Glutamate Cycle (In The Gut)
Muscle
Amino Acid Glutamate

Liver

Glutamate Urea Blood Glutamate Ketoacids

Glutamine Keto Acid

TCA GNG

Glutamine
Gut

Nitrogen

Controlling Protein Uptake


Tissue stress will cause an increase in protein uptake.

Exercise!


More later!

If You Love It, Let It Go…


Muscle releases AAs in response to metabolism changes.


Glutamine: 50% of AA released.


Remember damage during exercise. Remember GNG.



Alanine: 30% of AA released.


The Rule…Its Exception


Most AAs are released in proportions similar to that in the muscle.


Exceptions: BCAA, Glutamate, Aspartate, Asparagine

Amino Acids and ATP




Amino Acids can be broken down to make ATP. This is called AA Oxidation.


BCAA

Branch Chain AA


Oxidation of BCAA






Large source of ATP production for muscle. Most active when muscle glycogen is low. Stimulates GNG by preventing pyruvate conversion to Acetyl CoA.

BCAA Oxidation and TCA


BCAA oxidation steals α-ketogluterate from the TCA for transamination.


This slows the TCA through catapleurosis.



Later, some of the BCAA are converted to succinyl CoA, replenishing the TCA.


The TCA speeds back up via anapleurosis.

Exercise
Amino Acid and Energy Pathway Changes.

Post-exercise




Synthesis and breakdown both increase, but synthesis outpaces breakdown. This effect lasts for more than two days.

I Guess This Is Goodbye…


Low intensity exercise
 

20% drop in muscle glutamate. No change in muscle alanine levels. 40% drop in muscle glutamate. Alanine levels rise as glutamate levels fall. No change in glutamine levels.



Moderate intensity exercise
 





Where does the glutamate go?

Disappearing Glutamate




Glutamate is involved in the conversion of pyruvate to alanine for GNG. This creates α-ketogluterate.
 

Added to the TCA – anapleurosis. More ATP made by TCA/ETS.

Glutamine – Glutamate Cycle (GNG version) Step 2
Muscle Blood Liver

Pyruvate

Glucose

Glutamate
Glutamate

Urea

Alanine a-ketogluterate

Alanine

Krebs

Plasma Changes


Blood levels of AA also change with exercise.


Glutamate decreases.


Where does it go? And why? Where does it come from?



Alanine increases.




Glutamine increases.
What is the job of glutamine?  What is the initial cost of glutamine?


Import and Export






Muscular intake of glutamate increases 1-3 fold. Glutamine and alanine release increases 2-9 fold. Why?

I Can Change!
 



Exercise = Increased ATP demand. To meet this demand the aerobic system increases production up to 80-fold. This means that every intermediate much increase.


How?

Anapleurosis

Faster, faster…




To fill the anapleurotic demands of the TCA, glycolysis must run faster during exercise. Remember the role of pyruvate?
Glutamate Alanine
a-ketogluterate

Pyruvate

Acetyl Co A

TCA

Anapleurosis

Very Important Sugar


Glycogen is very important during exercise.
 



It is an energy source. It supplies pyruvate to be turned into alanine. Why?

Nitrogen removal and anapleurosis

Water Sucks!


Supplementing with carbohydrates during high intensity exercise, delays fatigue.

Alternative Fuels




If sugar is not consumed, we oxidize BCAA for energy. This uses the enzyme



Branch-chain alpha-ketoacid dehydrogenase BCKADH

BCKADH
 

Steals TCA intermediates. Stimulated by low glycogen.


No glucose for anapleurosis.



What happens next?

Premature Fatigue

Nitrogen Disposal
It’s a dirty job…

Are You The Keymaster?
 

Three key converstions: Amino Acid Α-ketoacid
  

Alanine Glutamate Aspartate

Pyruvate α-ketogluterate Oxaloacetate

 Aminotransferase


is the key!

Alanine Aminotransferase  Aspartate Aminotransferase

Alanine Amino Transferase
ALT




Changes alanine to pyruvate, and vice versa. Uses the glutamate/α-ketogluterate conversion to donate or accept the amine group.

Alanine to Pyruvate

Aspartate Amino Transferase
AST




Changes aspartate to OAA, and vice versa. Uses the glutamate/α-ketogluterate conversion to donate or accept the amine group.

Aspartate to OAA

The Common Bond




Both ALT and AST use the reversible reaction: Glutamate α-ketogluterate to carry the NH3 group to and from their respective reactions. This is why we don’t have a special enzyme for this reaction.

Help from Vitamins


Vitamin B6


Acts as a Cofactor for the aminotransferases.

Get the N Out of Here!


Nitrogen is excreted under two main conditions:
 

Protein intake is too high. AA are being broken down to aid in GNG.



What AA are used most for N export?

Please Pass the N


Nitrogen disposal happens in many steps.
    

Transamination Send new AA to the liver Deaminate Make urea Excrete

Transamination



Three key converstions: Amino Acid Α-ketoacid
  

Alanine Glutamate Aspartate

Pyruvate α-ketogluterate Oxaloacetate



Aminotransferase is the key!
 

Alanine Aminotransferase Aspartate Aminotransferase

Return to sender
 

N is sent to the liver. The most common AA sent are:
 

Alanine Glutamine



Why did we send AA to the liver before?

Deamination


Once in the liver, the AA has two options to get rid if its N.


Transamination


AST Glutamate Dehydrogenase



Deamination




Both methods will get the N to the urea cycle.

UREA!!
 

Urea is formed in the urea cycle. The two entry points into the urea cycle are:


Carbamoyl phosphate


Made by: Carbamoyl Phosphatase



Aspartate



Once formed, the urea can be sent to the kidneys to be excreted.

The Nitrogen Removal Story
AminoAcids α-ketogluterate Glutamate α-ketoacid OAA

Glutamate Dehydrogenase
α-ketogluterate
NH3 Carbamoyl CO2 Phosphatase Carbamoyl Phosphate

AST
α-ketogluterate
Aspartate

Urea Cycle

Urea

blood
Creatine Kinase

Glucose HK/GK Synthase NADPH

DNA RNA Ribose

CH3-CH2-(CH2)n-CH2-COOH fatty acid

ATP
Glycogen
Creatine

NADPH G6P PPP PFK PEP Pyruvate alanine NADPH

Phosphorylase
L I V E R

fatty acid synthesis

Phosphagen System

Gluco Neo Genesis

Malonyl CoA
Acetyl CoA Carboxylase

fatty acid
CH3-CH2-(CH2)n-CH2-COOH carnitine

OAA

Acetly CoA

+ OAA

Citrate

OAA

Pyruvate Acetyl CoA

CH3-CH2-(CH2)n-CH2-COOH

FADH2 fatty acid oxidation

Oxidation Hydration

KETONE BODIES
Citrate

NADH

Oxidation

OAA
Thiolysis fatty acid - 2 + Acetyl CoA

Krebs Cycle  KG

glutamate

glutamine

Protein  amino acids  ketoacids

CO2

UREA
L I V E R

NH4 + CO2 Carbomoyl Phosphate

ATP

NADH FADH2

UREA CYCLE
H+

eH+ H+ H+ H+

O2

-

+
H2O

ETS WEINERT

H2O

aspartate


				
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