Amino acids

Amino acids

Structure

  • Consists of a carbon atom attached to a/an:
  • Only L-form amino acids are incorporated into proteins.
  • There are 20 standard proteinogenic amino acids in humans.

Properties

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.
  • Hydrophilic AA R groups are polar.
    • 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.
    • All AAs have at least two ionizable groups, each with its own acid dissociation constant (pKa).
    • 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

Aspidic glue!

  • 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

His basic lies argitate me

Amino acid derivatives

Catabolism of amino acids

Overview of amino acid catabolism

Biochemical reactions of amino acid metabolism

Transamination

Since it is involved in most transamination reactions, glutamate is a very important part of AA metabolism.

Deamination

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

Decarboxylation

  • Description: release of the α-carboxyl group of an AA via splitting of CO2
  • Examples: : synthesis of biogenic amines via L-amino acid decarboxylase (also known as DOPA decarboxylase, tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase), which also uses PLP

Catabolism of the carbon skeleton of amino acids

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

  1. Glucogenic amino acids
  2. Ketogenic amino acids: lysine and leucine are metabolized to acetyl-CoA, then either:
  3. Mixed gluconeogenic/ketogenic amino acids: metabolized to acetyl-CoA and glucogenic byproducts (fumarate, succinyl-CoA)

Lysine and leucine are the only pure ketogenic AAs.

References:[1]

Urea cycle

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

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

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 synthesis!

From urea, one NH2 group is provided by NH4+ from carbamoyl phosphate, one NH2 group is provided by aspartate, and the -C=O group comes from bicarbonate!

Do not confuse urea with uric acid from purine metabolism!

Synthesis of nonessential amino acids

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
Cysteine
Serine
  • 3-phosphoglycerate (in multiple steps)
Glycine
Alanine

Conditions associated with amino acid metabolism

  • 1. Anand CV, Anand U. Text book error: Threonine is ketogenic too. Biochem Educ. 1992; 20(3): pp. 183–184. doi: 10.1016/0307-4412(92)90073-U.
last updated 12/11/2019
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