Lecture 18 - Enzyme mechanisms + Biochemical signaling

Question 1

What is serine protease?

Answer 1

-class of protease that uses serine at its active site to catalyze proteolytic reactions

Question 2

what are examples are serine proteases?

Answer 2

• trypsin, chymotrypsin, elastase

- digestive enzymes

Question 3

where are digestive enzymes synthesized? stored?

Answer 3

• pancreas

- stored in an inactive form called zymogens

Question 4

what is trypsinogen activated by?

Answer 4

-by selective proteolysis by a primer enteropeptidase

Question 5

what happens once trypsinogen is activated?

Answer 5

-trypsin cleaves other trypsins, chymotrpysins and elastases

Question 6

how is selectivity achieved?

Answer 6

-by binding pocket geometric and charge selectivity

Question 7

How does trypsin work?

Answer 7

-by a catalytic triad with Ser, His and Asp at the catlytic center

Question 8

what is the mech for trypsin?

Answer 8

-transfer of an H+ to His-57 is stabilized by Asp-102 and makes Ser-195, a potent nucleophile

Question 9

What is a lysozyme?

Answer 9

-lysozyme cleaves glycosidic bonds in peptidoglycans on cell walls of bacteria

Question 10

what is the best studied lysozyme?

Answer 10

from hen egg white

Question 11

What is the substrate of lysozyme?

Answer 11

-a polysaccharide composed of alternating N-acteylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc)

Question 12

there are ___ ____ binding sites in a lysozyme

Answer 12

5 sugar binding sites: A through E

Question 13

All but ____ accommodate a sugar ring perfectly

Answer 13

D

Question 14

how does a sugar fit in the D binding site?

Answer 14

-fourth sugar is heavily distorted away from its chair conformation

Question 15

What are the 2 ionic residues that are involved with lysozyme?

Answer 15

Glu-35

Asp-52

Question 16

what do Glu-35 and Asp-52 do?

Answer 16

• positioned close to the C1 atom of the distorted sugar

- help hydrolyze the glycosidic bond between site D and E

Question 17

What are enzyme cofactors?

Answer 17

-needed to complete the catalytic centers of some enzymes

Question 18

What is apoenzyme?

Answer 18

inactive enzyme without its cofactor

Question 19

What is Holoenzyme?

Answer 19

active enzyme complete with its cofactor

Question 20

what are common essential enzyme cofactors?

Answer 20

many inorganic metal ions EX: Fe, Cu, Zn, Mn, Co etc.

Question 21

What else can cofactors act as?

Answer 21

-coenzymes

Question 22

what are coenzymes

Answer 22

-a cosubstrate that is regenerated by the reaction

Question 23

what are two main regulators of the many control points in the metabolic cycle?

Answer 23

1. intracellular mechanisms

2. intercellular signaling

Question 24

what do hormones carry?

Answer 24

intercellular biochemical signals

Question 25

how do hormones generally work/

Answer 25

-generally released into the blood stream, so organs, including the one they are not targeted for, all receive the signal

Question 26

The response level of an organ to a particular hormone is related to the _____ of receptors

Answer 26

density

Question 27

where are hormones synthesized?

Answer 27

-in a small number of endocrine glands

Question 28

What are 3 things that hormones chemically include?

Answer 28

1. peptides or polypeptides (insulin)
2. steroids (cortisol, glucocorticoids)
3. amino acid derivatives (epinephrine)

Question 29

What are 3 types of control mechanisms of hormones?

Answer 29

1. enzyme activation/inhibition via second messengers (G-proteins and cyclic AMP)
2. stimulation of the synthesis of particular proteins through activation of specific genes (steroids work on nucleus to modulate gene expression)
3. selective increases in the cellular uptake of certain metabolites (certain ion channels are gated by hormones)

Question 30

What are 2 types of hormone receptors?

Answer 30

1. intracellular

2. membrane-bound receptors

Question 31

what is an example of an intracellular hormone receptor?

Answer 31

nuclear receptors which exert their effects at the gene level

Question 32

what is function of a membrane-bound hormone receptor?

Answer 32

affects transmembrane message relaying

Question 33

How do peptide hormones work?

Answer 33

EX: insulin

• designed to be released by the cell
• synthesized by the secretory pathway

Question 34

how are all known polypeptide hormones synthesized?

Answer 34

-in an inactive (the “pro”) form (proinsulin)

Question 35

how is the active hormone formed from the pro form?

Answer 35

cleaving

Question 36

how is the peptide synthesized?

Answer 36

in the “prepro” form

Question 37

what does the “prepro” form mean?

Answer 37

signal sequence required in the secretory pathway (preproinsulin)