Pathways in Amino Acid Metabolism

Pathways of Amino Acid Degradation

Pathways in Amino Acid Metabolism

AAs are the building blocks of animal body.

The body cannot conserves as free molecules, but its had to converse to peptide, protein hormone form, or catabolite to ammonia( fish), urea( mammals), uric acid(birds, reptiles )

The terms ‘ammoniotelic’, ‘ureotelic’and ‘uricotelic’are used to indicate the forms of N excretion in the respective groups of animals.

Key Reactions

All animals have the capacity to use or salvage metabolic ammonia in key assimilation reactions involving glutamate dehydrogenaseand glutamine synthase.

The major sites of amino acid metabolism are gut, muscle, liver, and brain.

Glutamate dehydrogenase (GDH)

GDH is a key enzyme in AA metabolism due to its involvement in both the synthesis of glutamate and its breakdown by the reversible reaction.

a-Ketoglutarate+Ammonia+NAD(P)H <--->Glutamate+NAD(P)

This reaction represents an oxidative deamination requiring either NAD+ or NADP+. The pathway enables the synthesis of the NEAAs and the degradation of all amino acids.

Aminotransferases (transaminases)

Aminotransferases catalyses the transfer of an amino group from one amino acid (AA) to a keto acid to form another amino acid.

In general terms be:

Donor AA + Acceptor a-keto acid -> Product AA + Product a-keto acid

Two examples :

Aspartate+ a-Ketoglutarate -> Glutamate + Oxaloacetate
Glutamate + Pyruvate -> Alanine + a-Ketoglutarate

-This certainly is the case in microbial metabolism, for example in the rumen.

-Within animal tissues a- -keto acids are readily only a limited number of transaminated to their respective amino acids.


The initial step in the degradation of most AA involves a transamination reaction which coupled with the GDH results in the production of ammonia.

The liver is the primary site for coupled reactions of this, enabling
degradation of all amino acids.

The ammonia may be re-utilized or, because of its toxicity, converted into urea or uric acid in the liver prior to excretion via the kidneys.

Skeletal muscle is the major site for the transamination of the three BCAA, leucine, isoleucine and valine, and yielding the respective branched-chain keto acids (BCKA)



Glutamine synthase (GS)

The assimilation of ammonia may occur by a second pathway catalysedby glutamine synthaseas follows:

NH3
Glutamate --------> Glutamine
GS

Carbamoyl phosphate synthetase

A third mechanism for the assimilation of ammonia involves carbamoylphosphate synthetase:

Ammonia + CO2 + ATP --------> Carbamoylphosphate

Carbamoylphosphate then enters the urea cycle by combining with ornithine, thus enabling the excretion of waste N in mammals.

Oxidases

In animals only amino acids of the L-configuration can be used.
D-isomers of AA may be utilized by animals, by conversion of these isomers to the L –forms using D-AA oxidases, requiring FAD as cofactor.

The a-keto acid then yield the L-amino acid.

This reactions enables animals to use D-methioninewith up to 90% efficacy.

Decarboxylases

The reactions lead to the formation of bioactive molecules such as neurotransmitters.

The synthesis of histamine is also brought about by a decarboxylaseby histidinedecarboxy lasecatalyses

Phenylalanine hydroxylase

Hydroxylases play a key role in animal metabolism.

The enzyme catalyses the formation of tyrosine from phenylalanine.

Animals can synthesize tyrosine as long as sufficient quantities of phenylalanine are present in the diet.

Tyrosine is a component of proteins, and provides the aromatic ring for the synthesis of thyroxine, adrenaline (epinephrine) and noradrenaline (norepinephrine).

Arginine Metabolism

Arginine has recently play role as an intriguing amino acid in animal metabolism.

Its function as a precursor of proline, polyaminesand nitric oxide (NO) for optimal lactational performance.

Urea cycle

The metabolism of arginine, ornithine, citrulline and argininosuccinate is linked in a pathway that enables mammals to dispose of excess N from amino acids.

The liver is the primary site for this activity.

Waste N enters the urea cycle as carbamoyl phosphate, synthesized from ammonia, waste N also enters the cycle directly, via aspartic acid.

Arginase exists in two forms. Arginase I is a cytosolic enzyme whereas Arginase II occurs in the mitochondria.

Many extra-hepatic tissues contain both forms, including the mammary gland.

Arginaseis found in the liver and kidney of birds, with higher activity.

Uric Acid Pathway

The uric acid pathway is a major route for the disposal of waste N in avian species.

Nitric oxide

The synthesis of nitric oxide (NO) from arginine is depicted as follows:

The reaction is catalysedby various isoforms of NO synthase.

Inducible (iNOS) and constitutive (cNOS) forms have been identified in the cytosol.

The iNOSproduces large and sustained quantities of NO.

The cNOSgenerate intermittent low levels of NO.

Polyamines (spermine)

Ornithinedecarboxylase(ODC)(1) is a key enzyme in polyamine synthesis.

Polyamine production appears to be an essential in all tissuesthat are actively synthesizing proteins.

Polyamine is also an important for theaction of antinutritionalfactors inlegume seeds.

The involvement of methionine in polyamine synthesis imposes competing metabolic demands, particularly when the tissue supply of cysteineis critical.

Pyrimidines

The pyrimidinesnecessary for nucleotide production.

The synthesis of pyrimidinesalso involves glutamine and aspartate.

Pyrimidinesynthesis begins with the production of carbamoylphosphate.

Sulphur Amino Acids

The sulphuramino acids are methionineand cysteine.

Cysteine may undergo oxidation to form a disulphide bridge, yielding another sulphuramino acid, cystine.

Methionine plays a key role in metabolism as a donor of active methyl groups.

The initial formation of homocysteine which donates its sulphur atom to methioninefor the biosynthesis of cysteine.

Non-essential Amino Acids

Several of NEAA may become conditionally essential because endogenous of protein synthesis.

Stress caused by disorders of pregnancy and lactation and microbial pathogens may induce the need for NEAA.

The role of glutamate in animal metabolism and function, enabling the synthesis and breakdown of amino acids.

Glycine is another amino acid associated with multifunctional roles, being involved in the synthes of purines, creatineand haem and is a component of neurotransmitters.

Creatine supplements may exertbeneficial effects on pork quality.