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17 Cards in this Set

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What tags proteins for degradation in the proteasome?

Poly-ubiquitination

What happens to peptide fragments in protein degradation?

Proteolysis --> aa

Some: left intact for biosynthesis, aa - N disposal by urea cycle

C skeleton - glucose/glycogen synthesis, cellular respiration, fatty acid synthesis


What is ubiquitin?

Tag


Has an extended C terminus - linked to other proteins


Liked - poly-Ub


>4 effective signals for protein destruction #



What are the enzymes involved in Ub conjugation?

E1 - Ub activating enzyme


E2 - Ub conjugating enzyme


E3 - Ub-protein ligase



Explain the process of Ub conjugation

E1 - terminal COO- group linked to Cys residue in E1 - thioester bond


E2 - Ub shuttled to Cys residue in E2


E3 - Catalyses transfer of Ub from E2 to target protein

How is target specificity achieved?

Some E1, more E2, more E3


E3 provides most specificity


PEST sequence - aa sequence in several cell cycle proteins, targets degradation




Interaction of E3 with target protein - regulated by phosphorylation of target protein

What is the major site of degradation?

Liver

Is amino group or carbon skeleton removed first?

Amino group

What is the point of release in amino acid degradation?

Glutamate


Oxidatively deaminated to yield NH4+

What does aminotransferase do?

Catalyses transfer of an α-amino group from an α-amino acid to an α-ketoacid.


Asp + a-ketoglutarate <--> oxaloacetate + Glu




Reversible so also used for synthesis

What does glutamate dehydrogenase do?

Releases NH3 from glutamate


Activated by ADP/GDP




Eq favours glutamate



What is toxic NH3 converted into?

Urea

What is the alanine cycle?

Amino groups and carbons from muscle are transported to the liver




Muscles degrade aa for energy, N transaminated to pyruvate to form alanine.




Alanine is shuttled to the liver - Benters the urea cycle and pyruvate --> glucose

What is the result of defects in the urea cycle?

Hyperammonemia - elevated NH4+ in blood
- irreversible brain damage


Protein restricted diet

How are carbon skeletons in aa degraded?

C skeletons to major metabolic intermediates that can be converted into glucose or oxidised by TCA cycle



What is the source of non-essential amino acids?

a-keto acids by transfer of existing aa group by aminotransferase


Or diet

How is protein absorbed and digested?

Enzymes in pancreas.


Enzyme in stomach - pepsin, pH 2


Specific transporters - take up aa and peptides in intestinal cells