Detailed Notes on Amino Acids in Metabolism

Amino acids functionally serve as building blocks for proteins and are critical in various metabolic processes in the body.
They can be stored in a protein amino acid depot within skeletal muscle.

The process by which proteins are broken down into their constituent amino acids.
Highlights the role of skeletal muscle in amino acid storage and mobilization.

In a fed state, if there is a deficiency of an essential amino acid (e.g., methionine), it hinders protein synthesis despite the availability of other amino acids.
- The body cannot produce proteins effectively without the complete essential amino acid profile.
Those excess amino acids that cannot be utilized for protein synthesis are oxidized.
The oxidation of amino acids is a costly metabolic process and could lead to wasted potential for gene expression.

The fate of amino acids is influenced by the physiological state; they can be oxidized or repurposed depending on tissue type (e.g., hepatocytes, pancreas).
If amino acids are abundant, they can be packaged into fatty acids; otherwise, they undergo oxidation.
Transamination can occur, where non-essential amino acids can be synthesized from essential ones.

The majority of dietary protein (approximately 99%) meets gene expression demands for biological functions such as:
- Antibody production
- Tissue repair and synthesis
Individual amino acids serve critical roles in biological functions:
- Leucine: Acts as a metabolic sensor for muscle protein synthesis, activating enzymes in the process.
- Tyrosine: Precursor to dopamine and norepinephrine, influencing neurotransmitter synthesis.
- Tryptophan: Precursor for serotonin synthesis.
- Glutamate: Functions as a neurotransmitter and assists in gene expression.

During a fed state with adequate carbohydrates and lipids, amino acids contribute to:
- Formation of neurotransmitters.
- Synthesis of blood proteins (e.g., albumin).
- Providing nitrogen for cell growth and proliferation.
- Supporting structural integrity of proteins and enzymes throughout the body.
In a low carbohydrate, fed state, amino acids may be deaminated to produce ATP or used for gluconeogenesis, aiding glucose production from pyruvate.

During fasting, protein catabolism occurs primarily in skeletal muscle, which serves as a functional depot for amino acids.
The drip of amino acids from muscle to blood gradually increases as one moves further from the last meal, predominantly driven by hormonal changes:
- Initially influenced by insulin and glucagon.
- Cortisol plays a critical role in increasing the flow from muscle as fasting continues.
Amino acids primarily released during this period are alanine and glutamine.
Increased proteolysis correlates with prolonged fasting and stress conditions.

The transition of amino acid release from the muscle is influenced by hormonal changes:
- Insulin decreases, while glucagon and cortisol increase during fasting, enhancing protein breakdown and amino acid mobilization.
Cortisol facilitates the transition from a slow drip of amino acids to a more significant release as fasting progresses.

Long-term fasting results in elevated nitrogen in the urine, indicating increased proteolysis.
In prolonged fasting, ketone bodies begin to spare lean body mass by reducing proteolysis, marking a shift towards fat utilization for energy.

In conditions requiring increased protein demand (e.g., wounds, infections), amino acids from muscle are redirected to support immune function and tissue repair.
Lean body mass becomes crucial for mounting an effective immune response, particularly in severe infections like sepsis.

Enterocytes absorb amino acids in the form of single amino acids and dipeptides, requiring ATP for active transport.
The absorption process for proteins is notably more energy-intensive than for carbohydrates and lipids.
Following absorption, single amino acids enter the portal circulation, primarily reaching the liver, pancreas, and other organs for metabolic functions.

Excess nitrogen from amino acids is detoxified in the liver and kidneys through the urea cycle, producing urea for excretion.
The urea cycle involves:
- Conversion of ammonia (toxic) to urea (non-toxic), allowing easy excretion through urine.
- Key enzymes in the cycle such as carbamoyl phosphate synthetase (CPS), ornithine, citrulline, and arginine play critical roles in nitrogen transformation and excretion.

Daily protein needs must be met through dietary intake to balance catabolism and anabolic processes.
Muscle serves as a key reservoir for amino acids, especially in times of metabolic stress, providing a crucial source during fasting or heightened physiological demands.
Strategic intake of high-quality protein can optimize metabolic needs and support overall health, particularly for recovery, immune function, and maintaining lean body mass.