METABOLISM OF AMINO ACIDSYulia Suciati

OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT

ORGANISM

Ingested protein1

Biosynthesis 2 3

Protein

a AMINO ACIDS cDegradation (required) Nitrogen (ketogenic) Carbon skeletons (glucogenic) Used for energy pyruvate -ketoglutarate succinyl-CoA fumarate oxaloacetate

b cPurines Pyrimidines Porphyrins

Ureaacetoacetate acetyl CoA

Amino Acid Requirements of Humans -------------------------------------------------------------------Nutritionally Essential Nutritionally Nonessential -------------------------------------------------------------------Argininea Alanine Histidine Asparagine Isoleucine Aspartate Leucine Cysteine Lysine Glutamate Methionine Glutamine Phenylalanine Glycine Threonine Proline Tryptophan Serine Valine Tyrosine --------------------------------------------------------------------a Nutritionally semiessential. Synthesized at rates inadequate to support growth of children.

NITROGEN BALANCENitrogen 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 = Nin - Nout

Positive Nitrogen Balance

Negative Nitrogen Balance1. Stress

2. Decreased Intake

3. Lack of an essential AA

Metabolic Pool of Amino Acids

General reactions of amino acid catabolism O + NH4+deamination transamination

R

C O

COO-

NH2R CH

R

C NH2

COO-

COOR

CH

COO-

oxidative decarboxylation

NH3+ R

CH2

+

CO2

Transamination reactionThe 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 transaminasesAlanine-a-ketoglutarate transferase ALT (also called glutamate-pyruvate transaminase GPT)Aspartate-a-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.

ALT

Glucose-alanine cycleAlanine plays a special role in transporting amino groups to liver.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.

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 liverThe 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 SKELETONSCarbon 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

PhenylketonuriaHyperphenylalaninemia - 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 -ketoglutarate. Absence of -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.

GABA as neurotransmitter

Histidine Metabolism: Histamine FormationH N + NH3 CH2 CHCO2 -

Histidine decarboxylase

H N

CH2 CH2 NH2

N

Histidine

CO2

N

Histamine

Histamine: Synthesized in and released by mast cells Mediator of allergic response: vasodilation, bronchoconstriction

II] Serotonin Pathway:NH2 CH2CHCOOH O2 N H Tryptophan Tryptophan hydroxylase H2 O HOH2 biopterin

NH2 CH2 CHCOOH N H 5-OH Tryptohpan PLP CO2 HO CH2 CH2 NH2

H4 bioterin

decarboxylaseNADP+ NADPH(H+)

* Neurotransmitter * Founds in mast cells& platelets. * Vasoconstrictor for B.V.& bronchioles * Transmitter in GIT to release the peptide hormones.HO

N H 5-OH Tryptamine (Serotonin) CH3COSCOA N-Acetyl Transferase COASH CH2CH2 NHCOCH3 N H N-acetyl 5-OH tryptamine O-methyl Transferase CH3O SAM SAH CH2CH2 NHCOCH3

N H Melatonin (N-acetyl-5-methoxy-serotonin)

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

fumarate

Aceto acetate

Dopa & Dopamine

Melanine

Skatol & Indol

Melatonin

glucose

ketone

Nor epinephrin & epinephrine

Thyroxin

Anthranilic

Serotonin

Alanine

Nicotinamide

Acetoacetyl CoA

Amino acids as precursors of neurotransmitters

1. Arginine --------------NO 2.Tryptophan-----------Serotonin 3. Histidine--------------Histamine 4. Phenyl alanine------dopa,dopamine, NE&E 5.Glutamic acid--------GABA

ALHAMDULILLAH SEMOGA BERMANFAATYS/2011