AMINO ACIDS CATABOLISM

Fig. 23-1, p.630

Amino acids act principally as the building blocks and to the synthesis of variety of other biologically molecules.

When a.acids deaminated (removed the α-amino group), their C-keletons can be fed to TCA cycle.

They may be used as precursors of other biomolecules.

How are amino acids synthesized?

The α-amino group of glutamate and the side-chain amino group of glutamine are shifted to other compounds: transamination reactions

The biosynthesis of amino acids involves a common set of reactions

Reductive amination

Amidation

Glutamate is formed from NH4+ and α-

ketoglutarate in a reductive amination that requires NADPH. This reaction is catalyzed by glutamate dehydrogenase (GDH)

The conversion of Glutamate to Glutamine is catalyzed by glutamine synthetase (GS) that requires ATP

Combination of GDH and GS is responsible for most assimilation of ammonia into organic compound. However, the KM of GS is lower than GDH

Fig. 23-6, p.635

Transamination reactions: Role of Glutamate and Pyridoxal phosphate

Amino acids biosynthesis

Enzyme that catalyzed transamination require pyridoxal phosphate as coenzyme

Fig. 23-8b, p.637

Fig. 23-9, p.638

One-C transfer and the serine-family

In amino acid biosynthesis, the one-C transfer occurs frequently

E.g serine family (also include glycine and cysteine)

Ultimate precursor of serine is 3-phosphoglycerate (obtainable from glycolitic pathway)

The conversion of serine to glycine involves one-C unit from serine to an acceptor

This is catalyzed by serine hydroxymethylase, with pyridoxal phosphate as coenzyme

The acceptor is tetrahydropholate (derivative of folic acid) – its structure has 3 parts: a subtituted pteridine ring, p-aminobenzoic acid and glutamic acid

Fig. 23-12, p.641

Serine + tetrahydrofolate → Glycine + methylenetetrahydrofolate +H2O

Fig. 23-13, p.641

The conversion of serine to cysteine involves some interesting reactions

In plants and bacteria: serine is acetylated to form O-acetylserine (by serine acyltransferase, and acetyl-CoA as acyl donor)

Fig. 23-14, p.641

In animals: the reaction involves the amino acid methionine

Methionine (produced by reactions of the aspartate family) in bacteria and plants can be obtained from dietary sources – essential amino acids

Fig. 23-16, p.642

Table 23-1, p.643

What are essential amino acids?

• The biosynthesis of proteins requires the presence of all 20 amino acids• If one is missing or in short supply, the protein biosynthesis is inhibited

• Protein deficiency will lead to the disease kwashiorkor; severe in growing children, not simply starvation but the breakdown of the body’s own protein

Catabolism of amino acids

In catabolism, the amino nitrogen of original amino acid is transferred to α-ketoglutarate → glutamate, leave behind the C skeletons

Disposition of C skeletons There are two pathways of the breakdown of C

skeletons depends on type of end product: i. Glucogenic amino acid: yields pyruvate and OAA

on degradation (can be converted to glucose with OAA as intermediate)

Ii. Ketogenic amino acid: one that breaks down to acetyl-CoA or acetoacetyl-CoA to form ketone bodies

Table 23-2, p.644

Fig. 23-17, p.644

Excretion of excess nitrogen Excess nitrogen is

excreted in one of three forms: ammonia, urea and uric acid

Animal in aquatic env.: release as ammonia

Terrestrial animal: urea (soluble in water)

Birds: uric acid (insoluble in water)

Urea cycle Central pathway in

nitrogen metabolism

The nitrogen that enter urea cycle come from several sources

A condensation reaction bet. ammonium ion and CO2 produce carbamoyl phosphate in a reaction that requires of two molecules of ATP/carbamoyl phosphate

In human, urea synthesis is used to excrete excess nitrogen, after consuming a high-protein meal

The pathway is confined to the liver

The synthesis of fumarate is a link bet. the urea cycle and TCA cycle

p.646a

p.648

When amino acid catabolism is high, large amounts of glutamate will be present from degradation of glutamine, from synthesis via glutamate dehydrogenase and from transamination reaction.

Increase glutamate level leads to increase levels of N-acetylglutamate followed by increasing the urea cycle activity.