Chapter 30: Protein Turnover and Amino Acid Catabolism

Main idea of Chapter 30

Protein destruction is regulated and amino acids are recycled.

Main degradation system

Ubiquitin-proteasome system.

UPS steps

Tag → recognize → destroy.

Key signal for degradation

K48 polyubiquitin chain.

Minimum ubiquitin chain length

4 ubiquitins.

E1 function

Activates ubiquitin (ATP).

E2 function

Carries ubiquitin.

E3 function

Selects substrate (specificity).

Proteasome structure

19S cap + 20S core.

19S role

Recognize and unfold protein.

20S role

Degrade protein.

N-end rule

First amino acid determines half-life.

UPS signaling example

IκB degraded → NF-κB activated.

Oxygen sensing

HIF-1α degraded in normoxia, stable in hypoxia.

Nitrogen removal steps

Transamination → deamination.

Nitrogen hub

Glutamate.

Transamination cofactor

PLP (B6).

Deamination product

NH4+.

Muscle nitrogen shuttle

Alanine.

Safe nitrogen carrier

Glutamine.

Urea cycle function

Detoxifies ammonia.

Rate-limiting enzyme

CPS I.

Nitrogens in urea

NH4+ and aspartate.

Energy cost of urea cycle

3 ATP (4 bonds).

Purely ketogenic amino acids

Leucine and lysine.

PKU defect

Phenylalanine hydroxylase.

MSUD defect

BCKDC.

OTC deficiency

Hyperammonemia + orotic acid.

Big concept

Nitrogen is toxic, carbon enters metabolism.