Yulia Suciati METABOLISM OF AMINO ACIDS

OVERVIEW OF AMINO ACID METABOLISMENVIRONMENT ORGANISM

Ingested protein

Bio- synthesis

Protein

AMINO ACIDS

Nitrogen

Carbonskeletons

Urea

Degradation (required)123ab

PurinesPyrimidinesPorphyrins

cc

Used for energy

pyruvate-ketoglutaratesuccinyl-CoAfumarateoxaloacetate

acetoacetateacetyl CoA

(glucogenic)(ketogenic)

NITROGEN BALANCENitrogen balance = nitrogen ingested - nitrogen excreted (primarily as protein) (primarily as urea)

Nitrogen balance = 0 (nitrogen equilibrium) protein synthesis = protein degradationPositive nitrogen balance protein synthesis > protein degradationNegative nitrogen balance protein synthesis < protein degradation

N balance = Nin - Nout

Positive Nitrogen Balance

Negative Nitrogen Balance1. Stress2. Decreased Intake3. Lack of an essential AA

Metabolic Pool of Amino Acids

General reactions of amino acid catabolism

Transamination reactionThe first step in the catabolism of most amino acids is removal of a-amino groups by enzymes transaminases or aminotransferasesAll 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 transaminasesALT Alanine-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.

Glucose-alanine cycleAla 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 CYCLEmitochondriacytosolFunction: 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 PhenylalaninePhenylalanine 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 -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.Phenylketonuria

GABA as neurotransmitter

Histidine Metabolism: Histamine FormationHistidineHistamineHistidinedecarboxylaseCO2Histamine: Synthesized in and released by mast cellsMediator of allergic response: vasodilation, bronchoconstriction

II] Serotonin Pathway:* Neurotransmitter

* Founds in mast cells& platelets.

* Vasoconstrictor for B.V.& bronchioles

* Transmitter in GIT to release the peptide hormones.

Glycine oxidation to CO2Glycine 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

Amino acids as precursors of neurotransmitters1. Arginine --------------NO2.Tryptophan-----------Serotonin3. Histidine--------------Histamine4. Phenyl alanine------dopa,dopamine, NE&E5.Glutamic acid--------GABA

ALHAMDULILLAHSEMOGA BERMANFAATYS/2011