Introduction to Nitrogen Catabolism

Functions of proteolysis

• Removes misfolded as well as old and damaged proteins,

• Supplies essential amino acids when dietary intake is insufficient,

• Controls cell-cycle transitions and cell disjunction.

Functions of digestion of dietary proteins

Supplies both nutritionally essential and nutritionally nonessential amino acids.

de novo synthesis

-Provides nonessential amino acids for protein synthesis

-Fixes amino acid pools into different tissues

-adjusts energy metabolism by controlling concentrations of central pathway metabolites, allowing cells to adapt to metabolic stress

-required for nucleotides, hemes, hormones, and neurotransmitters

What are the essential amino acids?

P Proline

V Valine

T Threonine

T Tryptophan

I Isoleucine

M Methionine

H Histidine

A Alanine

L Leucine

L Lysine

Define proteostasis

Protein homeostasis regulated by several controlled processes

Why are proteostatic mechanisms so essential to the cell?

they ensure that functional proteins are maintained at their correct concentrations and in the proper locations

prevent misfolding, aging, damage

Primary role of ubiquitin-proteasome system

Selective degradation of

short-lived or damaged

protein

Primary role of autophagy

Bulk degradation of

cytoplasmic components

Primary role of lysosomal degradation

Degradation of endocytosed

proteins, membrane proteins,

and long-lived intracellular

materials

How are proteins degraded in digestion?

Sequential proteolysis:

-Stomach (acid + pepsin) → denaturation

+ initial cleavage

-Small intestine (pancreatic enzymes) →

bulk digestion

How are enzymes released in digestion

As zymogens to prevent self-digestion

Ex: Trypsinogen > Trypsin (activated in intenstine)

What’s the end result of digestion

Amino acids +di/tripeptides are absorbed then circulate to the liver

Then feed into nitrogen metabolism

Describe zymogens

-Prevent self-digestion

-Activated by proteolytic cleavage

How is pepsin activated

Low pH and autocatalysis

What is trypsin’s role

Central activator in the intestine. Protease activation is a cascade, activates other proteases

What get absorbs and how in the stomach

Amino acids and di-/tripeptides get absorbed in the small intestine and across intestinal epithelial cells

How does absorption works

-Transport into enterocytes

-Amino acids via transporters

-Di/tri-peptides via transporter

Inside the cell:

peptides convert to amino acids which circulate to the liver

When do amino acids undergo oxidative degradation?

• Leftover amino acids from protein turnover aren't needed for new protein synthesis

• Dietary (ingested) amino acids exceed the body's needs

• Proteins are used as fuel when carbs are unavailable or not properly used (e.g., diabetes, fasting)