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Amino acids

Last updated: August 12, 2021

Summarytoggle arrow icon

Amino acids are organic compounds that consist of a carbon atom attached to a carboxyl group, a hydrogen atom, an amino group, and a variable R group (side chain). In humans (and other eukaryotes), there are 21 different proteinogenic amino acids, 20 of which are encoded for protein synthesis by the genetic code, as well as selenocysteine, which is integrated via a special translation mechanism. They can be divided into essential amino acids (cannot be synthesized by the body) and nonessential amino acids (can be synthesized by the body). Amino acid derivatives include glycine, glutamate, histidine, arginine, tryptophan, and phenylalanine. Amino acid catabolism can occur via different metabolic routes, each with a specific purpose, including the production of metabolic fuels (e.g., pyruvate, acetyl-CoA), reuse in the synthesis of new proteins, and the creation of amino acid derivatives. Deficiencies in these metabolic routes can lead to a variety of conditions, which are covered in more detail in “Disorders of amino acid metabolism,” “Hyperphenylalaninemia,” and “Hyperammonemia.”

Structure

  • Amino acid (AA) 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 21 standard proteinogenic amino acids in humans

Properties

Essential or nonessential

Essential vs. nonessential amino acids
Group Amino acid Synthesis Catabolic product

Essential amino acids

Leucine (Leu)

Lysine (Lys)

  • Cannot be synthesized (must be consumed)

Phenylalanine (Phe)

Isoleucine (Ile)

Threonine (Thr)

Tryptophan (Trp)

Methionine (Met)

Valine (Val)

Arginine* (Arg)

Histidine* (His)

Nonessential amino acids

Alanine (Ala)

Asparagine (Asn)

Aspartate (Asp)

Glutamate (Glu)

Glutamine (Gln)

Glycine (Gly)

Proline (Pro)

Serine (Ser)

Cysteine** (Cys)

Tyrosine** (Tyr)
Conditional amino acids

*Arginine and Histidine may become essential (thus require supplementation) during times of increased demand (e.g., during illness, growth phases such as pregnancy or childhood).

**Cysteine and Tyrosine are synthesized from essential AAs.

For essential AAs, think PVT (Private) TIM HALL: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine

To remember glucogenic AAs, think: Arges Met His Valentine and gave her sweets.

For his movie roles, Brad PITT may eat a lot (glucogenic) or diet (ketogenic): Phenylalanine, Isoleucine, Threonine, Tryptophan

For ketogenic AAs, visualize 2 L-shaped keys: Leucine and Lysine.

Hydrophobic or hydrophilic

Hydrophobic vs. hydrophilic amino acids
Features Hydrophobic amino acids Hydrophilic amino acids
Location during protein folding
  • Normally settle within the protein core
  • On the surface
R groups
  • Nonpolar
  • Polar
Examples
  • Aromatic: Phe, Trp
  • Aliphatic: Gly, Ala, Met, Pro, branched chain AAs (Val, Leu, Ile)
  • Uncharged: Tyr, Ser, Thr, Cys, Asn, Gln
  • Charged: Asp, Glu, Arg, Lys, His

Acid-base properties

  • Overview
    • 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 become polar/hydrophilic.
    • Acid dissociation constant (pKa)
      • Indicates the strength of a weak acid or base
      • Defined as the pH at which the ionized and unionized forms exist in equal concentrations
    • 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.
  • Acidic amino acids: Side groups are negatively charged at body pH (both have a pKa of ∼ 4). ;
    • Asp
    • Glu
  • 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. They could be found in histones binding negatively charged DNA.
      • Lys: pKa of 10.5
      • Arg: pKa of 12.5

His (histidine) lies (lysine) are (arginine) base (basic amino acids).

Overview

Transamination

Glutamate is involved in most transamination reactions and a very important part of AA metabolism.

Deamination

Glutamate dehydrogenase can use either NAD+ or NADP+ as a cofactor.

Decarboxylation

Overview of the amino acid carbon skeleton metabolism
Category Amino acids Metabolism routes
Glucogenic amino acids

Alanine

Asparagine

Aspartate

Cysteine

Glutamate

Glutamine

Glycine

Histidine

Methionine

Proline

Serine

Valine

Mixed glucogenic/ketogenic amino acids

Isoleucine

Phenylalanine

Threonine

Tryptophan

Tyrosine

  • See “Routes of AA carbon skeleton metabolism” below.
Ketogenic amino acids

Leucine

Lysine

Routes of AA carbon skeleton metabolism

Lysine and leucine are the only pure ketogenic AAs.

Urea cycle reactions
Reaction Substrate Enzyme (+ site of reaction) Product(s) Special features
1. Entry into the urea cycle: creation of carbamoyl phosphate from HCO3 and NH3
  • Carbamoyl phosphate

2. Creation of citrulline from carbamoyl phosphate and ornithine

  • Citrulline
3. Creation of argininosuccinate from citrulline and aspartate
  • Argininosuccinate synthetase (cytosol)
  • Argininosuccinate
4. Hydrolysis of argininosuccinate to arginine and fumarate
5. Hydrolysis of arginine to urea and ornithine

Urea cycle steps (Ornithine, Carbamoyl phosphate, Citrulline, Aspartate, Argininosuccinate, Fumarate, Arginine, and Urea): “Outrageously Cynical Criticism Antagonizes All my Friends At University”

The rate-limiting step of the urea cycle involves CPS1.

Location of the CPS1 enzyme is “M1tochondria.”

NH2 groups for urea production are derived from carbamoyl phosphate and aspartate, whereas the carbon group comes from bicarbonate.

The mitochondrial carbamoyl phosphate synthetase 1 of the urea cycle should not be confused with the cytosolic carbamoyl phosphate synthetase 2, which is an important enzyme for pyrimidine biosynthesis.

Do not confuse urea with uric acid from purine metabolism.

Overview of nonessential AA synthesis

Amino acids

Development from Responsible enzyme(s)
Glutamate
Glutamine
Aspartate
Asparagine
Arginine and Proline
  • Reversal of the degradation reaction of glutamate
  • N/A
Cysteine
Serine
  • 3-phosphoglycerate (in multiple steps)
  • N/A
Glycine
  • N/A
Alanine

Hyperammonemia

  1. Murray Moo-Young. Comprehensive Biotechnology. Newnes ; 2011