Disposal of Nitrogen: Urea

Question 1

What is the N-end rule?

Answer 1

The N-terminal amino acid determines the rate at which a protein is degraded; dictates the half life

Question 2

Which N-terminus amino acids are long-lived/stabilizing?

Answer 2

Met, Ala, Ser

Question 3

Which N-terminus amino acids are short lived/destabilizing?

Answer 3

Leu, Asp

Question 4

What are PEST sequences? What amino acids do they contain?

Answer 4

Sequences which dictate rapid degradation for the protein; Pro, Glu, Ser, Thr

Question 5

What are the two systems of protein degradation?

Answer 5

ATP-dependent Ubiquinone-proteasome system of the cytosol; ATP-independent degradative system of the lysosomes

Question 6

What type of proteins are typically degraded by the Ubiquitin/ 26S proteasome system?

Answer 6

Mainly endogenous proteins; short-lived or damaged proteins

Question 7

What are the three enzymes involved in the conjugation of ubiquitin to a protein substrate? What is the function of each?

Answer 7

E1: activates ubiquitin
E2: Conjugating enzyme- binds activated Ub
E3 ligase: Identifies protein to be degraded and interacts with E2-Ub to transfer Ub to substrate

Question 8

How does the proteasome recognize proteins to be degraded? What is its action?

Answer 8

The proteasome recognizes a poly-ubiquitin chain of 4 or more Ub molecules; it unfolds, removes Ub, and then cuts the protein into small fragments

Question 9

What degrades the small fragments of proteins resulting from proteasomal degradation into free amino acids?

Answer 9

Cytosolic proteases

Question 10

What proteins are degraded by the lysosomal pathway?

Answer 10

Cell-surface and exogenous proteins

Question 11

What enzymes are used by the lysosome to degrade proteins?

Answer 11

Acid hydrolases

Question 12

What are the three categories of Autophagy? What is each?

Answer 12

Microautophagy: direct engulfment of cytoplasmic material into lysosome
Macroautophagy: Used primarily to eradicated damaged cell organelles or unused proteins; double-membraned autophagosome fuses with lysosome
Chaperone-Mediated Microautophagy: Protein with hsc70 complex binds to chaperone protein which translocates the protein across lysosomal membrane

Question 13

Where are proteolytic enzymes that degrade proteins produced?

Answer 13

Stomach, pancreas, small intestine

Question 14

What is the function of HCl in the stomach?

Answer 14

Kills bacteria, denatures proteins, converts pepsinogen to pepsin

Question 15

What cells secrete pepsinogen?

Answer 15

Chief cells of the stomach

Question 16

What stimulates the secretion of pancreatic digestive enzymes?

Answer 16

Cholecystokinin and secretin

Question 17

What enzyme synthesized in the intestine releases the cycle of gastric proteolytic enzymes

Answer 17

Enteropeptidase

Question 18

What are the major pancreatic digestive enzymes

Answer 18

Trypsin, Chymotrypsin, Elastase, Carboxy-peptidases

Question 19

In which organ does digestion of oligopeptides occur?

Answer 19

Small intestine

Question 20

Which intestinal enzyme repeatedly cleaves the N-terminal residue from oligopeptides to produce smaller peptides/ free amino acids?

Answer 20

Aminopeptidase

Question 21

How are free amino acids, di- and tri-peptides absorbed into enterocytes?

Answer 21

Free amino acids via a Na+ linked secondary transport system; Di- and tri-peptides via an H+ linked transporter

Question 22

Where are free amino acids ultimately released following uptake into intestinal enterocytes; what is the mechanism of this movement?

Answer 22

Facilitated diffusion into portal system

Question 23

What is the ultimate fate of branched chain amino acids?

Answer 23

They are sent straight to muscles cells and are not metabolized by the liver

Question 24

What amino acids have decreased reabsorption in the kidneys in Cystinuria?

Answer 24

Cysteine, Ornithine, Arginine, Lysine

Question 25

What condition results from defective transport of Tryptophan?

Answer 25

Hartnup Disorder

Question 26

What are the two steps of amino acid catabolism?

Answer 26

1. Transamination 2. Oxidative Deamination

Question 27

What molecule accepts the amino group from almost all amino acids in the transamination process? What molecule does it become?

Answer 27

Alpha-ketogluterate; glutamate

Question 28

Which amino acids do not undergo transamination? How do these amino acids lose their amino groups?

Answer 28

Lysine and theonine; deamination

Question 29

What enzymes catalyze transamination reactions? How are they named?

Answer 29

Aminotransferases; named after the specific amino group donor

Question 30

Which aminotransferase transfers the amino group from alanine to alpha-ketogluterate to form glutamate in amino acid catabolism?

Answer 30

Alanine Aminotransferase (ALT)

Question 31

Which aminotransferase transfers the amino group from glutamate to oxaloacetate?

Answer 31

Aspartate Aminotransferase (AST)

Question 32

What is the mechanism of aminotransferases?

Answer 32

They transfer the amino groups to pyridoxal phosphate (active B6), which subsequently reacts with an alpha-keto acid to form amino acid

Question 33

What enzyme accomplishes the oxidative deamination of glutamate? What are the end products of this reaction?

Answer 33

Glutamate dehydrogenase; alpha-ketoacid and ammonia

Question 34

What coenzymes are used in deamination? What is the difference?

Answer 34

NAD+ (oxidative deamination) or NADP+ (reductive deamination)

Question 35

What enzymes catalyze the oxidative deamination of D-amino acids? In which organs and organelle are located? What coenzyme is required?

Answer 35

D-amino acid oxidases; liver/kidney; peroxisomes; FAD

Question 36

What enzyme catalyzes the conversion of glutamate to glutamine? What catalyzes the revese reaction?

Answer 36

Glutamine synthetase; Glutaminase

Question 37

What is the glucose-alanine cycle?

Answer 37

Glutamate dehydrogenase links muscle ammonia to alpha-ketogluterate to form glutamate, which donates the amino group to pyruvate to form alanine, which is transported to the liver. In the liver alanine loses its amino group to form ammonia and pyruvate. Pyruvate undergoes gluconeogenesis to form glucose which is returned to muscles.

Question 38

What activates carbonyl phosphate synthase I?

Answer 38

N-acetylglutamate

Question 39

What are the two major reasons for hyperammonia?

Answer 39

Acquired hyperammonia resulting from liver disease | Hereditary deficiency of urea cycle enzymes

Question 40

What kind of mutation in what enzyme results in hyperinsulin/hyperammonia syndrome?

Answer 40

Gain of function mutation in glutamate dehydrogenase

Question 41

What are the biochemical effects of HI/HA syndrome?

Answer 41

More glutamate is converted to alpha ketogluterate--> more glucose--> hyperinsulinism; decreased [glutamate] --> reduced N-acetylglutamate--> reduced urea synthesis (hyperammonia)