Proteins and Health Implications

Learning Objectives

• Explain how nutrition interacts with a person's genetic and epigenetic makeup to influence protein synthesis and health.
• Describe the nutritional challenges of vegetarian and vegan diets and strategies to ensure nutritional adequacy.
• Explain protein complementation and risks associated with inadequate protein intake.

Metabolic Fate of Dietary Protein

Metabolism and Function

• Upon absorption, amino acids (AAs) enter the bloodstream and travel to the liver via the portal vein.
• Amino acids are used for numerous purposes in the body, with an amino acid pool formed from dietary protein and endogenous proteins.

Liver Processing of Amino Acids

• The liver is the primary processing facility for amino acids absorbed from digestion.
• Approximately 30% of AAs are released into systemic circulation from the liver.
• Key functions of the liver concerning amino acids include:
  1. Protein Synthesis: Formation of plasma proteins and other compounds like carnitine.
  2. Synthesis of Non-Essential Amino Acids: The liver can produce non-essential amino acids from intermediates.
  3. Oxidation for Energy: AAs can be oxidized for energy, particularly during low carbohydrate availability.
  4. Conversion to Glucose or Fatty Acids: AAs can be utilized to produce glucose or fatty acids when required.

Protein Synthesis

Central Dogma of Molecular Biology

• The central dogma describes the flow of genetic information as:
  • ext{DNA}
    ightarrow ext{RNA}
    ightarrow ext{Protein}
• Transcription: DNA is transcribed to messenger RNA (mRNA) in the nucleus.
• Translation: mRNA is translated on ribosomes to synthesize proteins.

Process of Protein Synthesis

1. mRNA Template Production: DNA serves as a template to create strands of mRNA, which carry the instructions for protein synthesis.
2. Transport of mRNA: The mRNA exits the nucleus through the nuclear membrane while the DNA remains protected inside.
3. Ribosome Interaction: mRNA attaches itself to ribosomes, which are the protein-making machinery of the cell.
4. Amino Acid Collection: Transfer RNA (tRNA) collects amino acids and transports them to the mRNA sequence based on codon recognition.
5. Amino Acid Assembly: As the ribosome moves along the mRNA, it joins amino acids in the prescribed sequence to form a protein strand, with tRNA returning for additional amino acids.
6. Protein Release: When all amino acids have been added, the completed protein is released, with mRNA and ribosome dissociating. This process can incorporate 40 to 100 amino acids per second in active cells, highlighting the efficiency of protein synthesis.

Synthesis of Non-Essential Amino Acids (NEAA)

Carbon Skeleton Formation

• Amination: The process involves the incorporation of an ammonium ion ( ext{NH}_4^+) to form an amino group, which is then attached to a carbon skeleton.
• Transamination: This reaction transfers an amino group from one amino acid to a carbon skeleton, forming a different amino acid. It is defined that for this context, ammonium, ammonium ion, and amino groups can be treated as equivalent.

Amino Acids Used for Energy

• Energy Derivation: Under conditions of low carbohydrate availability, amino acids can be utilized to produce glucose via gluconeogenesis. An example is the conversion of alanine to glucose, pyruvate, and ultimately glucose.
• The body disposes of nitrogen during this process, which mainly occurs via the urea cycle.

Conversion of Amino Acids to Triglycerides or Glucose

• Excess amino acids may be converted to triglycerides (TG) or glycogen, again with nitrogen being disposed of effectively by the body.
• The conversion path includes alanine and ends up at acetyl CoA as part of metabolic processes.

Key Concept: No Amino Acid Storage

• The human body cannot store amino acids for later use. Unused amino acids are catabolized, and the process of deamination occurs, where the amino group is removed.
• The activity of the urea cycle in the liver increases with greater dietary protein intake, leading to elevated urinary excretion of nitrogenous waste products, along with excretion through skin and feces.

Protein Turnover

Rates of Turnover

• Protein turnover rates vary widely across different tissues and cell types and under various conditions such as disease or nutrient availability.
• Muscle Protein Synthesis (MPS) and Muscle Protein Breakdown (MPB) are fundamental components of the protein turnover process.

Cancer Cachexia

Definition

• Cancer cachexia is a complex metabolic syndrome defined by involuntary muscle loss and results in poor clinical outcomes and decreased survival odds.
• This condition negatively influences cancer treatment and affects most patients with advanced cancer who experience weight loss above 5%.

Dietary Treatment Guidelines

• According to the European Society for Clinical Nutrition and Metabolism (ESPEN), protein intake for cancer patients should range from 1.0 to 1.5 g/kg/day.
• Guidelines from the American Society of Clinical Oncology recommend that clinicians refer patients with cancer-related weight loss or appetite reductions to registered dietitians for nutrition assessment and counseling, emphasizing high-protein, high-calorie diets and avoiding fad diets.

Protein Deficiency and Malnutrition

Protein-Energy Malnutrition (PEM)

• Key forms of PEM are:
  • Marasmus: A severe form of malnutrition characterized by energy deficiency.
  • Kwashiorkor: A condition due to protein deficiency combined with adequate calorie consumption.

Effects of PEM

• Adults with PEM may face:
  • Muscle loss
  • Fatty liver development
  • Edema due to fluid retention
  • Decreased functionality across various physiological systems.

Age-Related Sarcopenia

Definition

• Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength, particularly impacting the elderly.

Nutritional/Lifestyle Interventions

• Suggested interventions include dietary supplements and targeted diets for older adults, an important demographic often facing increased muscle loss due to sedentary lifestyles.
• Emphasis on the quality of protein intake, particularly concerning sufficient leucine content and engagement in physical exercises, especially resistance training, to preserve muscle mass.

Protein Needs

Quantity vs Quality

• The balance between the quantity and quality of protein is crucial to maintain health. Needs can vary widely based on individual health requirements and activity levels.

Dietary Protein and Muscle Protein Synthesis

• Key determinants for optimal muscle protein synthesis include:
  • Type of Protein: Favoring those rich in essential amino acids (EAAs), especially branched-chain amino acids (BCAAs) like leucine. Recommended intake is about 3 g per meal.
  • Timing of Protein Intake: Consuming a protein-rich meal approximately every three hours to maximize protein synthesis and minimize muscle breakdown.

Optimal Protein Intake for Muscle Building

Recommended Daily Intake

• An intake of approximately 1.6 g protein/kg/day is optimal for muscle building.
• The highest potential benefit is noted with up to about 2.2 g protein/kg/day, beyond which no additional muscle-building benefits are typically realized.

Amino Acid Absorption Mechanism

Intestinal Structure and Function

• The intestinal endothelial cells are arranged back-to-back along intestinal villi, facilitating efficient absorption of free amino acids, dipeptides, and tripeptides.

Transport Mechanism

• Amino acid transport relies on active transport and facilitated diffusion methods, often linked with sodium-potassium pumps that utilize ATP for function.

Competition and Supplementation

• Different amino acids compete for transporters and carrier proteins, so single amino acid supplementation must be approached carefully to avoid competition issues.

Leucine Content of Various Foods

Plant-Based Diets

Nutritional Considerations

• Well-planned vegan and vegetarian diets can meet protein, energy, and micronutrient needs. However, certain nutrients may necessitate special attention:
  • Protein quantity (digestibility) and quality (e.g., lysine, leucine).
  • Micronutrients: Vitamins B12 and D, calcium, iron, zinc, and iodine.
  • Omega-3 fatty acids may be lacking in plant-based diets, requiring alternative sources.
  • Risk of deficiencies rises during pregnancy, lactation, infancy, and adolescence.

Benefits of Plant-Forward Dietary Patterns

• A well-planned plant diet can have various benefits:
  • Nutrient adequacy stemming from a diet rich in nutrient-dense foods.
  • Reduced inflammation and improved biomarkers related to dyslipidemia.
  • Positive environmental impact, such as lower land, water usage, and greenhouse emissions during food production.
  • Health benefits linked to weight control and reduced risk of non-communicable diseases (CVD, T2DM).

Conclusion

Big Picture

• Individual protein needs differ, and excess protein may be utilized for energy or stored as triglycerides.
• A diverse intake of protein-rich foods is essential to meet the needs for 9 essential amino acids (EAAs) and overall protein requirements.
• Meeting protein needs is generally achievable in most scenarios with careful dietary planning and attention, especially in plant-based diets.