Metabolic

Proteins are essential for cell structure, enzyme catalysis, and immune responses. The body uses proteins and other nitrogen-containing compounds as a building block or final product. Understanding protein metabolism is crucial for understanding numerous physiological processes

Proteins and Other Nitrogen-Containing Compounds

Definition: Proteins are large biomolecules consisting of one or more long chains of amino acids linked by peptide bonds
Function: Proteins perform a wide variety of functions in living organisms, including:
- Enzymes: Catalyze biochemical reactions
- Structural Proteins: Provide support and shape to cells and tissues
- Transport Proteins: Carry molecules across cell membranes or in the bloodstream
- Hormones: Act as chemical messengers
- Antibodies: Recognize and bind to foreign substances
- Contractile Proteins: Enable muscle contraction
Other Nitrogen-Containing Compounds: In addition to proteins, other important nitrogen-containing compounds include amino acids, nucleotides, creatine, porphyrins, and neurotransmitters
Key Metabolic Pathways
- Protein Synthesis: Production of proteins from amino acids
- Protein Degradation: Breakdown of proteins into amino acids
- Amino Acid Metabolism:
  - Transamination
  - Deamination
  - Urea Cycle
  - Synthesis of Specialized Products

Protein Synthesis

Purpose: To produce proteins from amino acids, based on the genetic code
Location: Ribosomes in the cytoplasm
Process
1. Transcription: DNA is transcribed into mRNA in the nucleus
2. Translation: mRNA is translated into a protein on ribosomes in the cytoplasm
  - mRNA binds to ribosomes
  - tRNA molecules bring specific amino acids to the ribosome
  - Amino acids are linked together by peptide bonds to form a polypeptide chain
3. Post-Translational Modification: The polypeptide chain is modified to form a functional protein
  - Folding: The polypeptide chain folds into a specific three-dimensional structure
  - Modification: Chemical groups may be added or removed (e.g., glycosylation, phosphorylation)
  - Cleavage: The polypeptide chain may be cleaved into smaller fragments
  - Quaternary Structure: Multiple polypeptide chains may assemble to form a complex protein
Regulation
- Transcription Factors: Regulate the transcription of genes
- mRNA Stability: Affects the amount of protein produced
- Ribosome Availability: Affects the rate of translation
- Post-Translational Modification: Can activate or inactivate proteins

Protein Degradation

Purpose: To break down proteins into amino acids
Location: Lysosomes and proteasomes
Process
1. Lysosomal Degradation
  - Proteins are taken up by lysosomes
  - Lysosomes contain proteases that degrade proteins into amino acids
2. Ubiquitin-Proteasome Pathway
  - Proteins are tagged with ubiquitin
  - Ubiquitinated proteins are degraded by proteasomes into small peptides
  - Peptides are further degraded into amino acids
Regulation
- Ubiquitin Ligases: Regulate the ubiquitination of proteins
- Proteasome Activity: Regulated by ATP and other factors

Amino Acid Metabolism

Purpose: To convert amino acids into other molecules, including energy, glucose, lipids, and specialized products
Transamination
- Transfer of an amino group from an amino acid to a keto acid
- Catalyzed by aminotransferases (transaminases)
- Requires pyridoxal phosphate (vitamin B6) as a cofactor
- Important for synthesizing non-essential amino acids
Deamination
- Removal of an amino group from an amino acid
- Produces ammonia (NH3)
- Ammonia is toxic and must be converted to urea for excretion
Urea Cycle
- Conversion of ammonia to urea
- Occurs in the liver
- Involves a series of enzymatic reactions
- Urea is excreted in the urine
Synthesis of Specialized Products
- Amino acids are used to synthesize a variety of specialized products, including:
  - Neurotransmitters (e.g., serotonin, dopamine)
  - Hormones (e.g., thyroid hormones)
  - Purines and Pyrimidines (building blocks of DNA and RNA)
  - Porphyrins (e.g., heme)
  - Creatine
Regulation
- Hormonal Control: Insulin, glucagon, and cortisol regulate amino acid metabolism
- Allosteric Regulation: Enzymes in amino acid metabolic pathways are regulated by allosteric effectors
- Substrate Availability: The availability of amino acids affects the rate of metabolism

Creatine Metabolism

Purpose: To synthesize creatine and phosphocreatine, which are important for energy storage in muscle cells
Process
1. Synthesis of Creatine
  - Arginine + Glycine → Guanidinoacetate + Ornithine (in kidney)
  - Guanidinoacetate + SAM → Creatine + SAH (in liver)
2. Transport to Muscle
  - Creatine is transported from the liver to muscle cells
3. Phosphorylation of Creatine
  - Creatine + ATP ↔︎ Phosphocreatine + ADP (catalyzed by creatine kinase)
4. Use of Phosphocreatine
  - Phosphocreatine is used to regenerate ATP during muscle contraction
5. Degradation of Creatine and Phosphocreatine
  - Creatine and phosphocreatine are spontaneously converted to creatinine
  - Creatinine is excreted in the urine
Clinical Significance
- Creatine kinase (CK) is used as a marker of muscle damage
- Creatinine is used as a measure of kidney function

Key Terms

Protein Synthesis: The production of proteins from amino acids
Protein Degradation: The breakdown of proteins into amino acids
Amino Acid Metabolism: The processing of amino acids for energy, glucose, lipids, and specialized products
Transamination: The transfer of an amino group from an amino acid to a keto acid
Deamination: The removal of an amino group from an amino acid
Urea Cycle: The conversion of ammonia to urea
Creatine: A molecule that stores energy in muscle cells
Phosphocreatine: A phosphorylated form of creatine that stores energy
Creatinine: A waste product formed from the breakdown of creatine and phosphocreatine
Ribosome: A cellular structure that synthesizes proteins
tRNA (transfer RNA): An RNA molecule that brings amino acids to the ribosome
mRNA (messenger RNA): An RNA molecule that carries the genetic code from DNA to the ribosome
Transcription: The process of copying DNA into RNA
Translation: The process of converting mRNA into a protein
Protease: An enzyme that breaks down proteins
Aminotransferase (Transaminase): An enzyme that catalyzes the transfer of an amino group
SAM (S-Adenosylmethionine): A methyl donor in biochemical reactions
SAH (S-Adenosylhomocysteine): A product of SAM-dependent methylation reactions
Hormones: Molecules synthesized from amino acids which act as a signaling molecule. Some examples include, thyroxine, epinephrine, and dopamine
Neurotransmitters: Signaling molecules responsible for transmitting messages between neurons. Amino acids are the building blocks of neurotransmitters such as GABA, glutamate, dopamine, serotonin, etc
Purines and Pyrimidines: These are nitrogenous compounds that are essential components of genetic material (DNA & RNA)
Porphyrins: This is a group of heterocyclic organic compounds, often forming a ring. A porphyrin is a crucial building block of heme-containing molecules that include hemoglobin and cytochromes

Biochemicals

Physiology