Metabolism of Amino Acids.

The fate of absorbed Amino Acids.

1) 2) 3) In the liver AAs are used for the synthesis of intrinsic proteins blood plasma proteins the liver provides for a balanced pool of free amino acids via synthesis of nonessential AAs and redistribution of nitrogen by transamination reactions. 4) for the production of specific nitrogen-containing compounds

Sources and fates of amino acids.

Nitrogen containing compounds (30 g/day)

porphyrins (heme, Hb, cytochromes) creatine purines, pyrimidines (DNA, RNA) neurotransmitters biogenic amines nicotinamide NAD+ melanins (pigments) ammonia Urea Uric acid

 The absorbed amino acids are primary used as building materials for the synthesis of specific tissue proteins, enzymes, hormones and other biologically active compounds. A certain number of amino acids undergo breakdown to yield the end products of protein metabolism (CO2, H2O and NH3) and to generate energy (10% of the daily requirement of the human organism in energy).

 Amino acid, like proteins are not deposited in the tissues for reserve purposes (in distinction to fats and glycogen). Amino acids concentrations in the blood of an adult human is maintained at a constant level (under the conditions of normal supply with dietary proteins).

Biological value of dietary proteins.

To have the high biological value protein should have

1) all essential amino acids in its composition (PVT TIM HALL)

Lack of any of the essential amino acids in the diet leads to a negative nitrogen balance, physical waste, growth retardation, nervous system disturbances and other pathologic symptoms.

1) and similar composition of amino acids of body proteins.

 The more close is the protein diet to the amino acid composition of body proteins, the higher is its biological value.
For instance, the proteins of meat, milk and egg are biologically of greater value for man (since their amino acid compositions are close to the amino acid composition of human tissues and organs).

 Biological value of proteins of animal origin is higher than proteins of vegetable origin.
Because of this reason, for the synthesis of the same amount of intrinsic body proteins, the human organism requires much more dietary vegetable proteins than animal proteins.

Protein reserves.
The term reserve proteins refers to

tissue proteins that can be easily mobilized to supply amino acid needs of
the body. Proteins of

liver,
muscles and blood plasma (albumin) can be used as
a specific reserve material. The liver and muscles are the first to lose mass, while the mass of brain or heart remains essentially unaffected.

Putrefaction of amino acids.

The intestinal microflora has a set of enzymes distinct from human enzymes (catalyze putrefactive breakdown of amino acids in the large intestine). The formation of both toxic products of amino acid breakdown (phenol, indole, cresol, skatole, hydrogen sulphide and methyl mercaptan) and non-toxic compounds (alcohols, amines, fatty acids, keto acids and hydroxy acids) are formed in the large intestine.

Putrefaction of sulphurcontaining amino acids.

In the course of gradual breakdown of

sulphur-containing

amino

acids

(cystine, cysteine and methionine)

hydrogen sulphide (H2S) and methyl mercaptan (CH3SH)

are formed in large intestine).

 Diamino acids (ornithine and lysine)

undergo decarboxylation to yield amines (putescine and cadaverine).

Ornithin

-CO2

putrescine

Lysine

-CO2

cadaverine

The
when

aromatic
subjected

amino

acids

(phenylalanine, tyrosine) and tryptophan,

to an analogous bacterial decarboxylation yield the relevant amines:

phenylethylamine, p-hydroxyphenylethylamine (tyramine), indolylethylamine (triptamine). Then gradual breakdown of the side chains takes place and toxic metabolites are formed cresol phenol, skatole and indole, respectively.

Tyrosine
-CO2

tyramine (p-hydroxyphenylethylamine)

cresol

phenol

Tryptophan
-CO2

tryptamine

skatole indole

 To be detoxified, these products are delivered, though the portal vein, to the liver where they become bound with activated

sulphuric acid or glucuronic acid

to produce non-toxic conjugated acids (e.g. phenol-sulfuric or skatoxylsulpfuric acid) excreted in the urine.

 Sulfuric and glucuronic acids are present in their active forms:

3-phosphoadenosine-5phosphosulphate (PAPS); uridine diphosphoglucuronic acid (UDP-glucuronate).

 Indole becomes bound in the form of a sulphuric acid ester.

Its salt, potassium

indoxyl sulphate

(indican) is excreted in the urine.

Determination of indican concentation in the human urine allows

to estimate the rate of protein putrefaction in the intestine as well as to diagnose the functional state of the liver.

Catabolism of amino acid carbon skeletons

The catabolism of the 20 amino acids involves the removal of -amino groups and then the breakdown of carbon skeletons 7 products are formed:

oxaloacetate, -ketoglutarate, pyruvate, fumarate, acetyl-CoA, acetoacetyl-CoA and succinyl-CoA.

Complete ketogenic AAS:

leucine and lysine

are converted to acetoacetate and are not converted to metabolites of CAC.

Glucoketogenic AAs are isoleucine, phenylalanine, tyrosine, tryptophan.

Isoleucine

AcetylCoA acetoacetate SuccinylCoA acetoacetate fumarate

Phenylalanine Tyrosine

Tryptophan

acetoacetate pyruvate

 Other AAs are converted to metabolites of CAC or pyruvate and thats why they are glucogenic.

 AAs can also be classified as or essential, semiessential or nonessential according to whether or not they can be synthesized in humans.

Essential AAs (PVT TIM HALL): Phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, leucine, lysine. Semiessential AAs (HA): Histidine, arginine essential for
infants, not essential for adults.