Biochemistry II

Written by: Marcy Ziska Updated by: Michael Petrie

! ! ! !

Amino Acid Structure Amino Acid Metabolism Transamination and Deamination Nitrogen Disposal
! Urea Cycle

Muscle can only oxidize 6 Amino Acids

! LIVGAA

Liver can oxidize all 20 Amino Acids

AMINO ACIDS
!

KETOACIDS
!

Carbon skeletons with an amine group attached to alpha carbon Building blocks of peptides and proteins

Carbon skeletons without an amine group to alpha carbon Entrance molecules for metabolic pathways

AMINO ACID
! ! !

ALPHA KETO ACID

! ! !

Nonessential Amino Acids

! Alanine ! Asparagine ! Aspartate ! Cysteine ! Glutatmate ! Glutamine ! Glycine ! Proline ! Serine ! Tyrosine

Essential
! Arginine ! Histidine ! Methionine ! Theonine ! Valine ! Isoleucine ! Phenylalanine ! Tryptophan

Purely Ketogenic
! !

Glucogenic and ketogenic

! ! ! !

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.

! ! ! !

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 amino acid

!
! 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

Glucose Pyruvate Lactate

Glucose Pyruvate Lactate

Muscle

Liver

Glucose
Amino Acid -Keto Acid

Glucose Pyruvate
NH3

Pyruvate Alanine

Alanine

Muscle

Liver

Urea

Glutamate
Amino Acid -Keto Acid

Glutamate
PPP NH3

Glutamine

Glutamine

Muscle

Liver

Urea

! !

Muscle acquires Glutamate Glutamate receives a Nitrogen group from the metabolism of another AA (LIVGAA) by ____________________ Glutamine goes to other cells requiring nitrogen
! Liver ! Intestinal Cells ! Immune Cells

Glutamine gets a nitrogen group stolen turning back into glutamate by ____________________

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

Some are exported more than imported

! !

Remaining Amino Acids are exported at the same rate they are imported, except LIVGAA
! LIVGAA are imported more

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 steals -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.

Amino Acid and Energy Pathway Changes

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

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

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?

Muscular intake of glutamate increases 13 fold compared to resting conditions Glutamine and alanine release increases 2-9 fold compared to resting conditions

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

To fill the anapleurotic demands of the TCA, glycolysis must run faster during exercise

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

! !

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

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

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

Both ALT and AST use the reversible reaction:

! Glutamate to -ketogluterate

Used to carry the NH3 group to and from their respective reactions

! !

Deliver Nitrogen to the liver

! Commonly in the form of Glutamine or Alanine when

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
!

from the muscle

Products from these two processes are sent to Urea Cycle

! ____________________ ! ____________________

! ! !

Uses the enzyme ____________________ Removes nitrogen 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

Transfers the amine group from ____________________ to ____________________ ! End products are ____________________ and ____________________ ! ____________________ enters the Urea cycle
!

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

The Nitrogen Removal

AminoAcids -ketogluterate Glutamate -ketoacid OAA

Glutamate Dehydrogenase
-ketogluterate NH3 Carbamoyl CO2 Phosphatase Carbamoyl Phosphate

AST
-ketogluterate Aspartate

Urea Cycle

Urea

blood
Creatine Kinase

Glucose HK/GK Synthase NADPH

DNA RNA

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

ATP Glycogen
Creatine

NADPH G6P Ribose PPP PFK PEP Pyruvate alanine NADPH

Phosphorylase
L I V E R

fatty acid synthesis

Phosphagen System

Gluco Neo Genesis OAA

Malonyl CoA
Acetyl CoA Carboxylase

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

Acetly CoA

+ OAA

Citrate

OAA

Pyruvate Acetyl CoA KETONE BODIES Citrate

FADH2 fatty acid oxidation

Oxidation Hydration

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 UREA CYCLE

ATP NADH FADH2

eH+ H+ H+ H+ H+

O2

+ H2O

ETS WEINERT

H2O

aspartate