AMINO ACID METABOLISMS

Amino acid structure

Essential amimo acids

Val, Leu Ile Phe Met, Thr, Lys, Arg*, Hys*, Trp

Non essential amino acids

Gly, Ala, Ser, Pro, Hyp1, Cys, Tyr, Asn, Gln, Asp, Glu, Hyl1

AMINO ACID METABOLISM

BODY PROTEINS

Proteosynthesis Degradation

AMINO ACIDSDIETARYPROTEINS

GLYCOLYSISKREBS CYCLE

Digestion

Transam

ination

NONPROTEINDERIVATIVESPorphyrinsPurinesPyrimidinesNeurotransmittersHormonesKomplex lipidsAminosugars

GLUCOSE CO2 KETONBODIES

UREA NH3

Con

vers

ion

(Car

bon

skel

eton

)

Enzymes cleaving the peptide bonds

Endopeptidases – hydrolyse the peptide bond inside a chainPepsin, trypsin, chymotrypsin

Exopeptidases – split the peptide bond at the end of a protein moleculeAminopeptidase, carboxypeptidases

Dipeptidases

Pepsin (pH 1.5 – 2.5) – peptide bond derived fromTyr, Phe,bonds between Leu and Glu

Trypsin (pH 7.5 – 8.5) – bonds between Lys a Arg

Chymotrypsin (pH 7.5 – 8.5) – bonds between Phe a Tyr

NH2 transamination keto acid

+ amino acid

R C H

COOH decarboxylation amine

deamination keto acid

General reactions of amino acids are transamination anddeamination of amino group

Decarboxylation reaction gives biologically active amines

General reactions of amino acids

The glutamate which is produced by these transaminase reactions is oxidatively deaminated by glutamate dehydrogenase to release ammonium:

Transamination reactions

Transamination reactions(enzymes aminotransferases)

(aspartate--ketoglutarate transferase)

(Alanine--ketoglutarate transferase)

Transaminases are enzymes which transfer the amino group from an amino acid to a keto acid, usually alpha-ketoglutarate, essentially swapping an amino group with a keto group:

another similar reaction yields more common products:

These reactions are mediated by pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin B6):

pyridoxal phosphate pyridoxamine phosphate

pyridoxamine phosphate pyridoxal phosphate

Clinicaly important transaminases

ALTAlanine--ketoglutarate transferase

Clinical marker for irreversibile liver damage

ASTaspartate--ketoglutarate transferase

Clinical marker for irreversibile myocardial damage

Amino acids with three carbons are converted to pyruvate:•Alanine •Serine •Cysteine

Serine is deaminated by serine dehydratase to form pyruvate + NH4+ in a reaction which doesn't involve the transaminase but does use pyridoxal phosphate (PLP) as a reactive group.

Similarly, threonine can be dehydrated and deaminated to yield pyruvate.

Glycine can be converted to serine for degradation, or it can be cleaved to release CO2, NH4+ and an activated one-carbon unit. In addition, three carbons from tryptophan are converted to pyruvate by way of alanine.

Amino acids with three carbons are converted to pyruvate

Amino acids with five carbons are converted to alpha-ketoglutarate:•Arginine •Glutamine •Histidine •Proline

These amino acids are first converted to glutamate which is transaminated to alpha-ketoglutarate.

Some amino acids are converted to succinyl-CoA:•Methionine •Valine •Isoleucine

These amino acids are converted to propionyl-CoA which is carboxylated to methylmalonyl-CoA which is converted to succinyl-CoA. This last step is an isomerization catalyzed by Methylmalonyl-CoA mutase, an enzyme which uses cobalamin (vitamin B12).

Degradation of valine, leucine, and isoleucine requires the oxidative decarboxylation of an alpha-keto acid.

If this enzyme is defective, these acids accumulate in the blood and urine, resulting in maple syrup urine disease (branched chain ketoaciduria).

This disease is characterized by physical and mental retardation.

Leucine and Lysine are converted to acetyl-CoA and acetoacetate:

A serious disease results from the inability to oxidize phenylalanine by a defective phenylalanine hydroxylase.

This results in high levels of phenylpyruvate developing (phenylpyruvate is the result of transamination of phenylalanine with an amino acid).

The disease is phenylketonuria (PKU), and results in severe mental retardation and shortens the life span so that half the carriers are dead at 20 and 75% are dead at 30 if it is untreated. It is a genetic disorder and can result from aberrant splicing of the normal phenylalanine hydroxylase transcript.

Therapy for the disease involves restricting the intake of phenylalanine, and must be started immediately after birth. Screening for the disease occurs at birth so that as many effects as possible can be avoided.

Phenylalanine and Tyrosine are converted to fumarate and acetoacetate

Degradation of aminoacids gives intermediates

for saccharides and lipides synthesis

The twenty common amino acids are degrade to a total of seven different compounds, all of which are related to the citric acid

cycle:

Interconversion of amino acids and intermediates of carbohydrate metabolism

Ala Hyp Leu IleArg Met LysAsp Pro PheCys Ser TrpGlu Thr TyrGlu ValGlyHis

Glucogenic ketogenic glucogenic + ketogenic

Amino acids

Enzymes which metabolised amino acides containe vitamines as cofactors

Vater soluble vitamins B

THIAMINE B1 (thiamine diphosphate) oxidative decarboxylation of -ketoacids

RIBOFLAVIN B2 (flavin mononucleotide FMN, flavin adenine dinucleotide FAD)oxidses of -aminoacids

NIACIN B3 – nicotinic acid (nikotinamide adenine dinucleotide NAD+

nikotinamide adenine dinukleotide phosphate NADP+)dehydrogenases, reductase

PYRIDOXIN B6 (pyridoxalphosphate)transamination reaction and decarboxylation

FOLIC ACID (tetrahydropholate)Meny enzymes of amino acid metabolism

Nitrogenous derivatives of amino acids

Glycine heme, purine, creatine, conjugation of bile acids

Histidinehistamine

Ornithine a arginincreatine, polyamines (spermidine, spermine)

Tryptophanserotonine (melatonine)

TyrosineEpinephrine, norepinephrine

Glutamic acid-aminobutyric acid (GABA)

Aspartame (NutraSweet) consists of a methly ester of L-aspartate and L-phenylalanine: