Amino Acids and Plasma Proteins

Amino Acid Classification

  • Glucogenic Amino Acids

    • Contribute to gluconeogenesis (GNG) directly or indirectly.

  • Ketogenic Amino Acids

    • Include Leucine and Lysine.

    • Give rise to acetyl-CoA which can convert to fatty acids or ketones (acetoacetate derived directly).

    • Cannot be converted to glucose.

  • Both

    • The 3 T's: Tryptophan, Tyrosine, and Threonine.

    • Phenylalanine.

    • Isoleucine.

Essential vs. Nonessential Amino Acids

  • Essential Amino Acids

    • Must be obtained through diet.

  • Nonessential Amino Acids

    • Synthesized by the body.

    • Examples:

    • Alanine, asparagine, aspartate.

    • Cyst(s) proliferate in the body: cysteine and proline.

    • The body can produce tyrosine from phenylalanine.

    • The 3 G's and the only S: Glutamine, Glutamate, Glycine, and Serine.

  • Conditionally Essential:

    • Arginine is considered conditionally essential during certain physiological states (e.g., growth).

Amino Acid Catabolism

  • Succinyl-CoA: VoMIT succs.

    • Valine

    • Isoleucine

    • Methionine

    • Threonine

  • Oxaloacetate: Oxen eat ASPARagus.

    • Aspartate

    • Asparagine

  • Fumarate: ASPirating my PHilly cheesesteak is TYRing.

    • Aspartate

    • Phenylalanine

    • Tyrosine

    • Between Asparagine and Aspartate, remember fumarATE leads to aspartATE.

  • Acetoacetate: TYRed LUCy made it 2 PA.

    • Tyrosine

    • Leucine

    • Phenylalanine (2 = aceTOacetate)

  • α-KG (alpha-ketoglutarate):

    • Includes Proline, Arginine, Histidine, and Glutamate/Glutamine.

  • Pyruvate:

    • Serine

    • Threonine

    • Cysteine

    • Alanine

    • Tryptophan

    • Glycine

    • Mnemonic: "Pyrate Sam's 3 Children All Try to Glyde."

  • Acetyl-CoA:

    • Isoleucine

    • Leucine/Lysine (the only 2 ketogenic amino acids)

    • Tryptophan

    • Threonine

  • Main Diagram: (from Capstone Slides dated 2/16/2026)

    • Asparagine, Aspartate, Alanine, Cysteine, Glycine, Serine, Threonine, Leucine, Tryptophan, Isoleucine, Glucose, Leucine, Tryptophan, Lysine, Phenylalanine, Tryptophan, Tyrosine, Phosphoenolpyruvate, Pyruvate, Acetyl CoA, Acetoacetyl CoA, Oxaloacetate, Aspartate, Phenylalanine, Fumarate, Citrate, Tyrosine, Arginine, Glutamate, Isoleucine, Succinyl, α-Keto, Glutamine, Methionine, CoA, glutarate, Threonine, Histidine, Proline, Valine.

Transamination and Nitrogen Metabolism

  • Focus on glutamine/glutamate/α-KG, which relate to transamination and nitrogen elimination.

    • Alanine Transamination Reaction:

    • Catalyzed by alanine aminotransferase (ALT) and pyridoxal phosphate (PLP).

    • Reaction: Alanine <--> Pyruvate + NH3.

    • Asparagine Reaction:

    • Reaction: Asparagine + asparaginase produces Aspartate + NH4+.

    • Aspartate Reaction:

    • Reaction: Aspartate <--> OAA (Oxaloacetate) <--> TCA cycle.

    • Proline's Role:

    • Can be metabolized into Glutamate.

Proline Metabolism

  • Degradation Pathways:

    • Proline can degrade into Glutamate or

    • Convert to Δ1-pyrroline-5-carboxylate which can produce either Ornithine or Proline (when Arginine/Ornithine are high).

Phenylalanine and Tyrosine Metabolism

  • Phenylalanine (Phe) and Tyrosine (Tyr)

    • Involved in various metabolic pathways:

    • Phenylketonuria (PKU) due to deficiency of phenylalanine hydroxylase.

    • Albinism (involves biopterin).

    • Tyrosinemia (Types 1 and 2), affecting breakdown pathways of phenylalanine and tyrosine leading to specific clinical symptoms like dark urine in Type 1.

    • Related products include DOPA, dopamine, melanin, and breakdown to fumarate/acetoacetate for energy.

Tryptophan Metabolism

  • Tryptophan (Trp) Breakdown Products:**

    • Generates N-formylkynurenine and related compounds, ultimately producing:

    • Serotonin, Melatonin: Key neurotransmitters linked to mood and sleep regulation.

    • Nicotinamide/B3/Niacin: Important for NAD(P)+ production and subsequent energy metabolism.

    • Clinical conditions include deficiencies leading to acidurias.

Methionine Metabolism

  • Methionine (Met) transformation pathways:

    • Methionine converts to S-adenosylmethionine (SAM), then to S-adenosylhomocysteine (SAH), subsequently formed to homocysteine.

    • Homocysteine can exit the pathway forming cystathionine via reactions with serine, leading to cysteine and a-ketobutyrate.

    • Implications include homocystinuria, characterized by increased thrombosis risk.

Cysteine (Cys) and its Importance

  • Cysteine can be synthesized from methionine with importance in various biological functions.

    • Notably produces taurine, which is essential for retinal health, bile synthesis, and serves as an inhibitory neurotransmitter.

Branched Chain Amino Acids (BCAA)

  • Focused on specific metabolism through the Branched Chain α-Keto Acid Dehydrogenase (BCKAD) complex.

    • Required cofactors: Vitamin B1 (TPP), B2 (FAD), B3 (NADH), B5 (CoA), and Mg2+.

    • Important BCAAs: Isoleucine, leucine, valine.

    • MSUD (Maple Syrup Urine Disease) is characterized by sweet-smelling urine due to high levels of branched-chain ketoacids.