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Yulia Suciati

METABOLISM OF AMINO ACIDS

OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT ORGANISM

Ingested protein

Bio- synthesis Protein

AMINO ACIDS

Nitrogen Carbon

skeletons

Urea

Degradation (required)

1 2 3

PurinesPyrimidinesPorphyrins

c c

Used for energy

pyruvateα-ketoglutaratesuccinyl-CoAfumarateoxaloacetate

acetoacetateacetyl CoA

(glucogenic)(ketogenic)

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 .

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

N balance = NN balance = Ninin - N - Noutout

Positive Nitrogen BalancePositive Nitrogen Balance

Negative Nitrogen BalanceNegative Nitrogen Balance

1. Stress

2. Decreased Intake

3. Lack of an essential AA

Metabolic Pool of Amino AcidsMetabolic Pool of Amino Acids

R COO-

+ NH4+

deamination

transamination C

R COO-

NH2

R COO-

NH2

R COO-

oxidativedecarboxylation

CH2

NH3+

R CO2+

General reactions of amino acid catabolism

Transamination reaction

The first step in the catabolism of most amino acids is removal of a-amino groups by enzymes transaminases

or aminotransferases

All aminotransferases have the same prostethic group and the same reaction mechanism.

The prostethic group is pyridoxal phosphate (PPL), the coenzyme form of pyridoxine (vitamin B6)

The fate of the amino group during amino acid catabolism

TRANSAMINATION

Clinicaly important transaminases

ALT

Alanine--ketoglutarate transferase ALT(also called glutamate-pyruvate transaminase – GPT)

Aspartate--ketoglutarate transferase AST(also called glutamate-oxalacetate transferase – GOT)

Important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection.

Glucose-alanine cycle

Ala is the carrier of ammonia and of the carbon skeleton of pyruvate from muscle to liver.The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.

Alanine plays a special role in transporting amino groups to liver.

According to D. L. Nelson, M. M. Cox :LEHNINGER. PRINCIPLES OF BIOCHEMISTRY Fifth edition

UREA CYCLE

mitochondria

cytosol

Function: detoxification of ammonia (prevents hyperammonemia)

Glutamate releases its amino group as ammonia in the liver

The amino groups from many of the a-amino acids are collected in the

liver in the form of the amino group of L-glutamate molecules.

Glutamate undergoes oxidative deamination catalyzed by L-glutamate

dehydrogenase. Enzyme is present in mitochondrial matrix. It is the only enzyme that can use either NAD+ or NADP+ as the acceptor of reducing

equivalents. Combine action of an aminotransferase and glutamate dehydrogenase referred to as

transdeamination.

FATE OF THE CARBON SKELETONS

Carbon skeletons are used for energy.

Glucogenic: TCA cycle intermediates

or pyruvate (gluconeogensis)

Ketogenic: acetyl CoA, acetoacetyl CoA,

or acetoacetate

Metabolism of some selected amino acids

Biosynthesis of Tyrosine from Phenylalanine

Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced state by the NADH-dependent enzyme dihydropteridine reductase

Hyperphenylalaninemia - complete deficiency of phenylalanine hydroxylase (plasma level of Phe raises from normal 0.5 to 2 mg/dL to more than 20 mg/dL).The mental retardation is caused by the accumulation of phenylalanine, which becomes a major donor of amino groups in aminotransferase activity and depletes neural tissue of α-ketoglutarate. Absence of α-ketoglutarate in the brain shuts down the TCA cycle and the associated production of aerobic energy, which is essential to normal brain development. Newborns are routinelly tested for blood concentration of Phe.The diet with low-phenylalanine diet.

Phenylketonuria

GABA as neurotransmitter

Histidine Metabolism: Histamine Formation

CH2CHCO2-

NH3

CH2CH2NH2

Histidine Histamine

Histidinedecarboxylase

CO2

Histamine: Synthesized in and released by mast cells

Mediator of allergic response: vasodilation, bronchoconstriction

II] Serotonin Pathway:

CH2CHCOOH

NH2

H2biopterinH4bioterin NH

CO2

CH2 CH2 NH2HO

CH3COSCOA

COASH

CH2CH2NHCOCH3HO

SAM

SAH

O-methylTransferase

CH2CH2NHCOCH3CH3O

NH2

CH2 CHCOOH

H2O hydroxylase

NADP+ NADPH(H+)

decarboxylase PLP

5-OH Tryptamine (Serotonin)

Melatonin

Tryptophan

5-OH Tryptohpan

N-AcetylTransferase

N-acetyl 5-OH tryptamine

(N-acetyl-5-methoxy-serotonin)

Tryptophan

* Neurotransmitter

* Founds in mast cells& platelets.

* Vasoconstrictor for B.V.& bronchioles

* Transmitter in GIT to release the peptide hormones.

Glycine oxidation to CO2

Glycine produced from serine or from the diet can also be oxidized by glycine decarboxylase (also referred to as the glycine cleavage complex, GCC) to yield a second equivalent of N5,N10-methylene-tetrahydrofolate as well as ammonia and CO2.

Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

Aromatic Amino Acids

Phenylalanine Tyrosine Tryptophane

fumarateAceto

acetateDopa &

DopamineMelanine

Norepinephrin

&epinephrine

Thyroxin

Skatol &Indol

Melatonin

Anthranilic Serotoninglucose ketone

Alanine Nicotinamide

AcetoacetylCoA

Amino acids as precursors of neurotransmitters

1. Arginine --------------NO2.Tryptophan-----------Serotonin3. Histidine--------------Histamine4. Phenyl alanine------dopa,dopamine, NE&E5.Glutamic acid--------GABA