#Protein metabolism

#Outline protein metabolism, including the effects of starvation

Proteins are polypeptides composed of amino acids linked by peptide bonds. They play a central role in structural function, enzymatic activity, and metabolic regulation.

There are 20 amino acids in the human body:

• 10 essential amino acids must be obtained from the diet
• 10 non-essential amino acids can be synthesised endogenously

#Protein sources

Protein is derived from dietary intake and endogenous turnover, where body proteins are in a constant state of:

• Breakdown → amino acids
• Resynthesis → protein

This dynamic balance allows adaptation to metabolic demands.

#Elimination

Amino acids are filtered at the glomerulus but almost completely reabsorbed in the proximal convoluted tubule (PCT) via Na+/amino acid symporters, a form of secondary active transport.

Amino acid excretion (and therefore protein losses) are minimal in health but increase in illness (e.g. critical illness, renal disease).

#Normal Protein Metabolism

#Protein Catabolism

Amino acids are metabolised via two key processes:

1. Oxidative Deamination

• Removes the amino group from an amino acid creating a keto acid + ammonia.
• Ammonia is subsequently converted to urea (in the liver) for excretion.

2. Transamination

• Transfer of an amino group to another molecule, forming a new amino acid.

When an amino acid loses its amino group by deamination or transmination, it leaves behind a carbon skeleton. These skeletons are metabolic substrates which can be used in many different pathways:

• Acetyl-CoA → ketogenesis
  • amino acids that are deaminated to form acetyl-CoA are known as ketogenic amino acids
• Pyruvate or citric acid cycle (CAC) intermediates
  • these substrates may enter the citric acid cycle (CAC) ir be used for gluconeogenesis

#Protein Synthesis (Anabolism)

Amino acids are used to synthesise proteins required by peripheral tissues. This occurs in ribosomes on the rough endoplasmic reticulum via mRNA translation. Proteins undergo post-translational modification (e.g. glycosylation) in the smooth endoplasmic reticulum.

#Protein Metabolism During Starvation

#Early Starvation

In the initial phase, protein is a key substrate for gluconeogenesis:

• e.g. Alanine is used for gluconeogenesis in the liver
• e.g. Glutamate is used for gluconeogenesis in the kidney s

#Intermediate Phase (4 - 24 days)

Beyond 4 days of starvation, there is a metabolic shift from gluconeogenesis towards lipid metabolism.

This represents a protein-sparing adaptation.

The peak protein loss in this period is 75 g/day.

#Prolonged Starvation (24 days - 8 weeks)

Ketogenesis becomes the primary energy source and the brain adapts to ketone utilisation.

Protein loss decreases significantly in this period to 20 g/day.

#Late Starvation (>8 weeks)

As fat stores become depleted:

• Protein again becomes the primary energy source
• Rapid protein breakdown occurs and losses may exceed 125 g/day.

This phase leads to critical loss of lean body mass and organ dysfunction