11-Amino Acids and Protein Metabolism

7/29/2019 11-Amino Acids and Protein Metabolism

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Biochemistry II

Written by: Marcy Ziska

Updated by: Michael Petrie


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!Amino Acid Structure

!Amino Acid Metabolism

! Transamination and Deamination

! Nitrogen Disposal! Urea Cycle


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! Muscle can only oxidize 6 Amino Acids

! LIVGAA

! Liver can oxidize all 20 Amino Acids


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AMINO ACIDS

! Carbon skeletons with an

amine group attached to

alpha carbon

! Building blocks of

peptides and proteins

KETOACIDS

! Carbon skeletons without

an amine group to alpha

carbon

! Entrance molecules for

metabolic pathways


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AMINO ACID

!

!

!

ALPHA KETO ACID

!

!

!


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! Nonessential Amino

Acids! Alanine

! Asparagine

!

Aspartate! Cysteine

! Glutatmate

! Glutamine

! Glycine

! Proline

! Serine

! Tyrosine

! Essential

! Arginine

! Histidine

! Methionine

!

Theonine! Valine

! Isoleucine

! Phenylalanine

! Tryptophan


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! Purely Ketogenic

!

!

! Glucogenic and ketogenic

!

!

!

!


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! Peptide absorption in the SI occurs more

readily than free AA absorption (2:1)

! Peptide absorption = 67%

! Free AA absorption = 33%! The liver is the primary site for AA uptake.

!

50-65% of AAs absorbed here.


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!Anaplerosis

! adding to a pathway

! Catapleurosis

! taking from a pathway! Deamination

!

Removal of nitrogen base! Transamination

! Transfer of nitrogen base from one amino acid

to an alpha keto acid, creating a new aminoacid


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!

! Active during exercise

! Lactate to liver, glucose to muscle

!

! Active during metabolism of AA in muscle

! Alanine to liver, glucose to muscle

!

! Most active during immune response

! Glutamate to muscle, glutamine to liver(mostly)

!Used during Pentose Phosphate Pathway


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Muscle

Glucose

Pyruvate

Lactate

Liver

Glucose

Pyruvate

Lactate


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Muscle

Glucose

Pyruvate

Alanine

Liver

Glucose

Pyruvate

Alanine

AminoAcid

-KetoAcid

Urea

NH3


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Muscle

Glutamate

Glutamine

Liver

Glutamate

Glutamine

AminoAcid

-KetoAcid

Urea

NH3

PPP


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! Muscle acquires Glutamate! Glutamate receives a Nitrogen group from

the metabolism of another AA (LIVGAA) by____________________

! Glutamine goes to other cells requiringnitrogen! Liver

! Intestinal Cells! Immune Cells

! Glutamine gets a nitrogen group stolen

turning back into glutamate by____________________


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! Muscle imports the LIVGAA Amino Acids

more than it exports them!

!

!

!

!

!

! Other AAs are imported in the same

proportion they are exported, ie import =export


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! Some are exported more than imported

!

!

! Remaining Amino Acids are exported atthe same rate they are imported, except

LIVGAA

! LIVGAA are imported more


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! Oxidation of BCAA

! Large source of ATP production for muscle

! Most active when muscle glycogen is low

! Stimulates GNG by preventing pyruvateconversion to Acetyl CoA


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! BCAA oxidation steals -ketogluterate

from the TCA for transamination.

! This slows the TCA through catapleurosis.

! Later, some of the BCAA are converted tosuccinyl CoA, replenishing the TCA.

! The TCA speeds back up via anapleurosis.


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Amino Acid and Energy Pathway Changes


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! Low intensity exercise

! 20% drop in muscle glutamate.

! No change in muscle alanine levels

! Moderate intensity exercise! 40% drop in muscle glutamate

!

Alanine levels rise as glutamate levels fall! No change in glutamine levels


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! Glutamate is involved in the conversion of

pyruvate to alanine for GNG.

! This creates -ketogluterate

!Added to the TCA anapleurosis! More ATP made by TCA/ETS


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! Blood levels of AA also change with

exercise.

! Glutamate____________________

Where does it go? And why?

!Alanine____________________

Where does it come from?

! Glutamine____________________

What is the job of glutamine?

What is the initial cost of glutamine?


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! Muscular intake of glutamate increases 1-

3 fold compared to resting conditions

! Glutamine and alanine release increases2-9 fold compared to resting conditions


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! Exercise = Increased ATP demand.

! To meet this demand the aerobic system

increases production up to 80-fold

! This means that every intermediate mustincrease

! How?

! To fill the anapleurotic demands of the

TCA, glycolysis must run faster during

exercise


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! If sugar is not consumed, we oxidize

BCAA for energy

! This uses the enzyme

! Branch-chain alpha-ketoacid dehydrogenase(BCKADH)

Steals Krebs cycle intermediates

Fatigue sets in sooner


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! Send Nitrogen to the liver

! Via Glutamine or Alanine

! Transaminate nitrogen from entering

Glutamine and Alanine! Deaminate new AA formed

! Send nitrogen products to Urea Cycle

! Excrete urea


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!ALT

! Changes alanine to pyruvate, and vice

versa

! Uses the glutamate/-ketogluterateconversion to donate or accept the amine

group


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!AST

! Changes aspartate to OAA, and vice

versa.

! Uses the glutamate/-ketogluterateconversion to donate or accept the amine

group


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! Both ALT and AST use the reversible

reaction:

! Glutamate to -ketogluterate

! Used to carry the NH3 group to and fromtheir respective reactions


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! Deliver Nitrogen to the liver!

Commonly in the form of Glutamine or Alanine whenfrom the muscle! In the liver, Glutamine or Alanine are deaminated,

their nitrogens are donated to -keto acid in the

liver (-ketoglutarate) resulting in Glutamate! Glutamate is then deaminated using one of two

processes!

____________________! ____________________

! Products from these two processes are sent toUrea Cycle


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! Uses the enzyme

____________________Removesnitrogen from Glutamate, turning it into -ketogluterate

! Reduces NAD+ to NADH! Creates Ammonia from the removed

amine group!Ammonia is combined with CO2 by____________________to Carbamyol

Phosphate! Carbamyol Phosphate enters the Urea


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! Transfers the amine group from

____________________to

____________________

! End products are____________________and

____________________

!____________________enters the Urea

cycle


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! Primary function to form Urea to excrete

nitrogen from the body

! The two entry points into the urea cycle

are:! Carbamoyl phosphate

Made by:____________________

!Aspartate

Made by:____________________

!

Urea is sent to the kidneys to be excreted


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The Nitrogen RemovalAminoAcids

Glutamate

Aspartate

OAA

-ketogluterate

-ketogluterate

-

ketogluterate

Carbamoyl Phosphate

Urea

Urea Cycle

-ketoacid

NH3

CO2

GlutamateDehydrogenase AST

Carbamoyl

Phosphatase

Glucose CH3-CH2-(CH2)n-CH2-COOHfatty acid

DNA

RNAblood


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Krebs

Cycle

+

-

NADH FADH2

Pyruvate

PFK

GlycogenSynthase

Phosphorylase

OAA

Citrate

KG

Acetyl CoA

HK/GK

Phosphagen System

ATP

Creatine

H+H+ H+

H+H+

ATP

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

fatty acid

carnitine

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

PyruvateOAA

OAA

PEP

Gluco

Neo

Genesis

Ribose

NADPH

NADPHG6P

Citrate

Acetly CoA OAA+

fatty acid

NADPHfatty acid

synthesis

alanine

glutamate glutamine

UREA

CYCLE

UREA

aspartate

NH4 + CO2

Carbomoyl

Phosphate

H O

fatty acid - 2 + Acetyl CoA

Oxidation

Hydration

Thiolysis

Oxidation

FADH2

NADH

RNA

ETS

e-

fatty acid

oxidation

PPP

LI

V

E

R

L

I

V

ER

KETONE

BODIES

Protein amino acids ketoacidsCO2

O2

H2O

Malonyl CoA

Acetyl CoA

Carboxylase

Creatine

Kinase

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11-Amino Acids and Protein Metabolism