- Consists of a carbon atom attached to a/an:
- Carboxyl group (-COOH)
- Hydrogen atom
- Amino group (-NH2)
- Variable R group (side chain): determines unique properties
- Only L-form amino acids are incorporated into proteins.
- There are 20 standard proteinogenic amino acids in humans.
Essential vs. nonessential and catabolic product
|Group||Catabolic product||Amino acid|
Essential amino acids: cannot be synthesized (must be consumed)
| || |
|Nonessential amino acids: can be synthesized|
| || |
|Conditional amino acids|
*AAs that may become essential (thus require supplementation) during times of increased demand (e.g., during illness, growth phases like pregnancy or childhood)
**AAs that are synthesized from essential AAs
Hydrophobic and hydrophilic
- During protein folding, hydrophobic AAs normally settle within the protein core and hydrophilic AAs are on the surface.
Hydrophobic AA R groups are nonpolar.
- Aromatic: Phe, Trp
- Aliphatic: Gly, Ala, Met, Pro, branched chain AAs (Val, Leu, Ile)
Hydrophilic AA R groups are polar.
- Uncharged: Tyr, Ser, Thr, Cys, Asn, Gln
- Charged: Asp, Glu, Arg, Lys, His
The net charge and thus polarity of AAs can change according to the surrounding pH and availability of H+ available for protonation.
- When charged, AAs are polar/hydrophilic.
All AAs have at least two ionizable groups, each with its own acid dissociation constant (pKa).
- pKa of the α-carboxyl group = 2
- pKa of the α-amino group = 9–10
- Acidic/basic AAs have another pKa for their ionizable side chain group, which varies.
- The net charge and thus polarity of AAs can change according to the surrounding pH and availability of H+ available for protonation.
Acidic amino acids: Side groups are negatively charged at body pH (both have a pKa of ∼ 4).
Basic amino acids
Weakly basic: Side group has no charge at body pH (∼ 7.4).
- His: pKa of 6
Side groups are positively charged at body pH.
- Lys: pKa of 10.5
- Arg: pKa of 12.5
- Weakly basic: Side group has no charge at body pH (∼ 7.4).
His basic lies argitate me
- Histidine: (+ vit. B6) → Histamine + CO2 (decarboxylation)
Overview of amino acid catabolism
- Metabolic routes: During protein catabolism (see “Protein degradation” in the learning card on ), amino acids may undergo different metabolic routes for different purposes, including:
- Sites of metabolism
Processes of AA metabolism
- Biochemical reactions of AA
- Catabolism of the carbon skeleton of amino acids: can be reused as part of carbohydrate or lipid metabolism, or the citric acid cycle
- The urea cycle: Excess nitrogen is converted to urea via the urea cycle and excreted in urine.
- Description: transfer of an amino group from an AA to an α-ketoacid for breakdown, or to an α-ketoacid to form a nonessential AA
- Transaminases, particularly:
- Important cofactor: pyridoxal phosphate (PLP), a derivative of vit. B6, used in transamination and decarboxylation reactions
- Location: Transaminases are found in most cells of the body, but they have greater concentrations in the liver and heart.
- Most common examples
- Description: reaction in which an amino group from an AA is released as ammonium
- Examples: of enzymes with their reactions
Overview AA carbon skeleton metabolism
There are 3 different routes for catabolism of the carbon skeleton, depending on the AA.
|Metabolism routes||Amino acids|
|Glucogenic amino acids|
|Mixed glucogenic/ketogenic amino acids|| |
|Ketogenic amino acids|| |
Routes of AA carbon skeleton metabolism
Glucogenic amino acids
- Route: metabolized to pyruvate and to metabolites of the citric acid cycle, then either:
- Pyruvate: product of glycine, alanine, serine, and cysteine
- Methionine and valine: metabolized to succinyl-CoA via propionyl-CoA and methylmalonyl-CoA
- Methionine cycle: Methionine → S-adenosylmethionine (SAM) → S-adenosylhomocysteine → Homocysteine → Methionine
- Ketogenic amino acids: lysine and leucine are metabolized to acetyl-CoA, then either:
Mixed gluconeogenic/ketogenic amino acids: metabolized to acetyl-CoA and glucogenic byproducts (fumarate, succinyl-CoA)
Tyrosine and phenylalanine: metabolized to fumarate und acetyl-CoA
- Tyrosine: transamination through tyrosine transaminase, that is then metabolized through multiple steps to fumarate and acetyl-CoA
- Phenylalanine: first metabolized to tyrosine via phenylalanine hydroxylase (requires O2 and the reducing agent tetrahydrobiopterin), then further metabolized as described above
- Tryptophan: metabolized to alanine and acetyl-CoA, thereby also creating nicotinamide
- Tyrosine and phenylalanine: metabolized to fumarate und acetyl-CoA
Lysine and leucine are the only pure ketogenic AAs.
- A cycle of reactions that produce urea ((NH2)2CO) from ammonia (NH3), bicarbonate (HCO3−), and the amino group of aspartate.
- Enables the excretion of nitrogen (in urine)
- Primarily occurs in the cytosol and mitochondria of liver cells, also in kidney cells
- Requires 3 ATP for energy
- Measured as blood urea nitrogen (BUN) for clinical use
Origin of ammonia: Ammonia develops as a product of various metabolic pathways throughout the body.
- Because of its toxicity, ammonia must be connected to glutamine or alanine for transportation.
- Glutamine cycle (most common): transport of ammonia as an amine group attached to glutamine to the liver
- Alanine cycle (especially from muscle): transport of ammonia as an amine group on alanine to the liver
|Urea cycle reactions|
|Reaction||Substrate||Enzyme (+ site of reaction)||Product(s)||Special features|
|1. Entering the urea cycle: creation of carbamoyl phosphate from HCO3− and NH3|| || || |
2. Creation of citrulline from carbamoyl phosphate and ornithine
| || |
|3. Creation of argininosuccinate from citrulline and aspartate|| || |
|4. Hydrolysis of argininosuccinate to arginine and fumarate|| || |
|5. Hydrolysis of arginine to urea and ornithine|| || |
|Overview of nonessential AA synthesis|
|Development from||Responsible enzyme(s)|
|Asparagine|| || |
|Arginine and Proline|| |
|Cysteine|| || |
- See for details of the following conditions
- Maple syrup urine disease
- Hartnup disease
Hyperphenylalaninemia: increased levels of phenylalanine in the blood
- Most common cause: PKU
- Deficiency (or any enzyme dysfunction) of tetrahydrobiopterin (BH4) synthesis → ↓ (BH4 cofactor for phenylalanine hydroxylase and tyrosine hydroxylase) + ↓ synthesis of serotonin (BH4 cofactor for tryptophan hydroxylase) → deficiencies of neurotransmitters
- Treatment: replacement of BH4 or L-Dopa+ 5-OH-Tryptophan
- Normal intracranial ammonia physiology
- If serum ammonia is elevated → increased glutamine and decreased glutamate → low GABA synthesis and GABAergic tone → typical features of hyperammonemic encephalopathy
- Acquired: most often in adults
Liver failure: naturally occurring nitrogenous wastes in the blood accumulate to toxic levels secondary to impaired urea cycle function in damaged hepatocytes and/or shunting of blood from the portal vein to collateral circulations.
- Manifests as hepatic encephalopathy
- Kidney failure: inability to excrete excess ammonia as urea
- Severe dehydration
- Small intestinal bacterial overgrowth: urease-producing organisms in the gut produce excess ammonia
- Liver failure: naturally occurring nitrogenous wastes in the blood accumulate to toxic levels secondary to impaired urea cycle function in damaged hepatocytes and/or shunting of blood from the portal vein to collateral circulations.
- Hereditary: most often in children but heterozygotes can present as older children or adults
- Acquired: most often in adults
- Clinical features
- Management: Depends on the underlying cause and should be conducted ASAP to prevent central nervous system morbidity and possible mortality.