Amino acid metabolism
Content of subsection:
- Introduction to protein metabolism and amino acids
- Degradation of amino acids
- Degradation of the carbon skeletons of amino acids
- Formation of non-essential amino acids in the human body
- Significant individual amino acid derivatives
Introduction to Protein and Amino Acid Metabolism
Introduction to Protein and Amino Acid Metabolism
Essential and Dispensable Amino Acids
Essential and Dispensable Amino Acids
Important Amino Acid Reactions
Important Amino Acid Reactions
Amino acid metabolism defects
Defects of Amino Acid Metabolism
Degradation of amino acids
Urea (Ornithine) Cycle
Glucose-alanine cycle
Alanine, on the one hand, participates in the transfer of ammonia through the blood, and on the other hand, through pyruvate, serves as an important source of carbon for the process of gluconeogenesis.
See Glucose Breakdown and Synthesis for more detailed information.
The glucose-alanine cycle is an interorgan metabolic pathway occurring between muscle cells and the liver.
- After pyruvate is formed in muscle cells, it undergoes transamination to form alanine.
- It is released into the blood, which transports it to the liver, where it is converted back into pyruvate by transamination , which can be involved in the process of gluconeogenesis.
- The resulting glucose enters the muscles through the blood and the whole cycle is closed.
The transferred amino group (ammonia) goes to the urea cycle.
Degradation of the carbon skeletons of amino acids
About twenty amino acids are incorporated into human proteins (there are 22 of them including selenocysteine and pyrrolysine ). Amino acids that are not used in metabolism for any reason, e.g. after they have been released from proteins, are not excreted as a whole, but are catabolized into smaller fragments. At the beginning of the degradation, the amino group is usually split off. Then the remaining carbon skeleton is broken down. The pathways through which this happens are variously complex. Here we will show the common mechanisms and give some examples.
The breakdown of the carbon skeleton of all amino acids ends in one of these seven substances:
- pyruvate,
- acetyl-CoA,
- acetoacetyl-CoA,
- α-ketoglutarate,
- succinyl-CoA,
- fumarate,
- oxalacetate.
These products then enter the energy metabolism. They can either be further oxidized to carbon dioxide and water in the Krebs cycle, or they can be converted to other fuels. Some can produce glucose , others only ketone bodies and fatty acids . Accordingly, we distinguish between so-called glucogenic and ketogenic amino acids.
Ketogenic amino acids include those that lead to the formation of acetyl-CoA and acetoacetyl-CoA – leucine and lysine (beginning with the letter L). Glucogenic amino acids include those that lead to the formation of the remaining five products - pyruvate , α-ketoglutarate , succ-CoA , fumarate or oxaloacetate - serine, threonine, cysteine, methionine, aspartate, glutamate, asparagine, glutamine, glycine, alanine, valine, proline, histidine and arginine.
There are also amino acids with two degradation products – one of them is glucogenic and the other is ketogenic. We call them keto and glucogenic amino acids – they include isoleucine, phenylalanine, tyrosine a tryptophan.
The following overview shows which amino acids are degraded into which products:
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1) Acetyl-CoA and acetoacetyl-CoA
- purely ketogenic are Lys and Leu, several other amino acids provide degradation products both glucogenic and ketogenic – Phe, Tyr, Trp, Ile;
2) α-ketoglutarate
- Five-carbon – Glu, Gln, Pro, Arg and His;
3) Suc-CoA
- non-polar amino acids – Met, Ile a Val;
4) Fumarate
- Phe, Tyr;
5) Oxalacetate
- four-carbon amino acids – Asp a Asn;
6) Pyruvate
- Cys, Ala, Ser, Gly, Thr, Trp.
Degradation of branched-chain amino acids – Val, Leu and Ile
It is characteristic of these amino acids that they are degraded not in liver cells, but mainly in extrahepatic tissues – high activity especially in muscle cells. These contain a specific transaminase producing the respective α-keto acids – the so-called keto analogues of branched amino acids . This transaminase is absent in liver cells. Keto analogs are converted to acyl-CoA derivatives by the action of a dehydrogenation complex , which catalyzes oxidative decarboxylation and dehydrogenation.
Formation of non-essential amino acids in the human body
We cannot synthesize essential amino acids in the human body - Phe, Trp, Val, Leu, Ile, Met, Thr and Lys.
Two amino acids are essential during the growth period of the body (the period of their increased consumption), when the rate of their synthesis is not fast enough to cover the body's demands - called conditionally essential amino acids - Arg, His.
Other amino acids are classified as non-essential amino acids.
Amino acid precursors:
1) Oxalate → Asp, Asn;
(2) α-ketoglutarate → Glu, Gln, Pro, (Arg and His);
(3) Pyruvate → Ala;
4) 3-phosphoglycerate → Ser, Cys and Gly;
5) Phe → Tyr.
Phenylketonuria (PKU)
Phenylketonuria is an autosomal recessivedisease (8-10 cases / 100,000 individuals) due to the absence or phenylalanine hydroxylase activity. It physiologically catalyzes the hydroxylation of Phe to Tyr. In the case of an enzyme defect, there is an alternative degradation of Phe - phenylpyruvate (transamination), phenylacetate, phenylacetate or phenylethylamine is formed. These substances accumulate in tissues and body fluids and cause a typical urine odour. Some of them cause severe brain damage.
Phenylketonuria was the first human genetic defect in amino acid metabolism to be discovered and is currently one of the diseases screened in all newborns. If we can recognize it at this age, we can prevent brain damage with a strict Phe-restricted diet.
For more information see Phenylketonuria.'
Significant derivatives of individual amino acids
Decarboxylation – formation of biogenic amines
Decarboxylation – formation of biogenic amines
Nitric oxide (NO)
Nitric oxide is a vasodilator produced by endothelial cells.
It is formed from L-arginine by a reaction catalyzed by NO-synthase.
NO-synthase occurs not only in endothelial cells, but also in some cells of the immune system and in some neurons. It is a cytotoxic substance.
Other important amino acid derivatives
Trp → melatonin
Phe and Tyr → thyroid hormones, melanin
Gly → heme, purines, creatine, conjugation with bile acids
Arg and Ornithine → creatine, polyamines (spermidine, spermine)
Gly, Glu, Asp → purines and pyrimidines
Cys → taurine
Melatonin
Thyroxine
Triiodthyronine
Part of the melanin polymer structure
Heme
Purine
Pyrimidine
Creatine
Spermidin
Spermin
Taurin
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-Triiodthyronine_Structural_Formulae_V2.svg)
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