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CAPILLARY

  • Capillary structures involve astrocytes and neurons.

  • References to compounds:

    • NH3 (ammonia)

    • GLU (glutamate)

    • GLN (glutamine)

    • Aromatic amino acids.

Metabolism of One-Carbon Fragments

Key Concepts

  • Discussion on one-carbon compounds with their structural depictions:

    • Methane (CH₄): Tetrahedral geometry with four hydrogen atoms.

    • Methyl group (−CH₃): One carbon with three hydrogens.

    • Methylene group (−CH₂−): Two hydrogens bonded to carbon.

    • Methenyl group (−CH=): A carbon with a double bond to another carbon.

    • Hydroxymethyl group (−CH₂–OH): A methylene group bonded to an -OH.

    • Formyl group (−CH=O): A carbon double-bonded to an oxygen and single-bonded to hydrogen.

    • Oxo or keto group (−(C=O)): Carbon double-bonded to oxygen.

    • Carboxylic acid (−(C=O)–OH): A carbon double-bonded to oxygen and also bonded to a hydroxyl group.

    • Carbon Dioxide (CO₂): A carbon atom double bonded to two oxygen atoms.

Key Components in One-Carbon Metabolism

  1. Tetrahydrofolate (THF): A coenzyme involved in one-carbon transfers.

  2. Vitamin B12: Essential for the function of several enzymes in the body, particularly in metabolism involving THF.

  3. S-Adenosylmethionine (SAM): A principal methyl donor in biological systems, crucial for transmethylation processes.

Sources of Carbon Substances

  • The carbon substances derived from the above components contribute to various metabolic pathways.

Folic Acid Derivatives

Structural Components

  • Folate Structure: Detailed depiction of folate, featuring pteridine and polyglutamate moieties.

  • Dihydrofolate (FH₂): A derivative of folate.

  • Tetrahyrdofolate (THF): The biologically active form, which facilitates the binding of one-carbon fragments.

Binding of One-Carbon Fragments to Folate

  • Binding Sites:

    • Carbon fragments can bind at N5 or N10 positions of THF, or both, forming the N5-C6-C9-N10 cycle.

  • Fragment Types:

    • N5 Methyl: Methyl group at N5 position.

    • N10 Formyl: Formyl group at N10 position.

    • N5-N10 Methenyl: Methenyl connection between N5 and N10.

Sources of Single-Carbon Fragments

Metabolites Involved

  • Amino Acids:

    • Serine (SER): Source of one-carbon units, particularly in the form of Methylene-THF.

    • Glycine (GLY): Provides one-carbon units through conversion to Methylene-THF.

    • Histidine (HIS): Intermediates include formimino-THF and methenyl-THF.

    • Tryptophan (TRP): Involves metabolism yielding formyl-THF.

  • Intermediate Structures:

    • Methylene-THF (−CH₂−) formed from serine and glycine metabolism.

    • Formimino-THF (−CH=NH) derived from histidine.

    • Formyl-THF (−CH=O) from tryptophan.

Utilisation of Single-Carbon Fragments

Biochemical Reactions

  • Reduction Process:

    • Methylene-THF is reduced to Methyl-THF.

    • Enzyme Involved: Methylenetetrahydrofolate reductase (MTHFR).

    • Reaction is irreversible:
      extMethylene−THF+extNAD(P)H<br>ightarrowextMethyl−THF+extNAD(P)+ext{Methylene-THF} + ext{NAD(P)H} <br>ightarrow ext{Methyl-THF} + ext{NAD(P)}^+

Methyl-THF in Metabolism of Sulfur-Containing Amino Acids

Key Processes

  • Methionine (MET): Involved in the cycle linked to SAM.

    • Conversion to S-adenosylmethionine (SAM) for methylation processes.

    • Further conversion to S-adenosylhomocysteine (SAH) and then to homocysteine (HCY), a substance that has health implications.

    • Enzymes: Methionine synthase (involving B12) and MTHFR play significant roles.

MTHFR Mutation and Disorders

Implications of MTHFR Defects

  • Associated with hyperhomocysteinemia, which can lead to cardiovascular and neurological issues.

  • Functional details:

    • Deficiencies in THF and alterations in folate metabolism due to MTHFR deficiencies.

    • The relationship between methylene-THF, SAH, SAM, MET, and HCY in metabolic pathways.

List of Relevant Acids

Various Acids Involved in Metabolism

  • Propionic Acid: C₃H₆O₂

  • Acetoacetic Acid: C₄H₆O₃

  • Pyruvic Acid and Lactic Acid: C₃H₄O₃ relevant in glycolysis and anaerobic metabolism.

Enzymatic Activities and Units

Assays for Specific Enzymes

  • Alanine Aminotransferase: Normal levels range from 0.17 to 0.78 μkat/L.

  • Aspartate Aminotransferase: Normal levels range from 0.16 to 0.72 μkat/L.

Specific Acid Structures

Chemical Structures

  • Various acids depicted, including:Glutamate, Glycine, Glutamine, Serine, Aspartic Acid, with structural details included for synthesis and metabolic pathways.

Amino Acids Focus

Main Amino Acids

  • Leucine, Valine, Isoleucine: Structure includes branched-chain components that play roles in protein synthesis.

  • Phenylalanine and Tyrosine: Important in neurotransmitter synthesis.

  • Arginine: Key in urea and nitrogen metabolism.

Urea Cycle Components

  • Urea: End product of nitrogen metabolism, critical for removing ammonia from the body.

  • Ornithine and Citrulline: Intermediates in the urea cycle, involved in detoxification of ammonia.

  • Carbamoyl Phosphate: Formed in the mitochondria as part of the urea cycle, linking to nitrogen metabolism.

These pages cover the metabolism of one-carbon fragments, highlighting vital biochemical pathways, the role of folate derivatives, the sources of carbon compounds from amino acids, specific enzymatic functions, and disorders arising from metabolic dysfunctions. Each section outlines essential components and connections necessary to understand underlying metabolic processes thoroughly.