Chapter 02

Enzymes

III

Regulation I

Mishkat Ihsan

Mishkat Ihsan

Key

Day Date Month Lecture # : tittle#

Key word material / explaination

Question answer

"

You can use

this section to test

yourself bycovering

the rightside p

and retain information

usingthis side ( left

side ) only"

# → number.

are you will findthe meaning of

each shortcut that is used above"

Mishkat Ihsan

Key

Sat 10 July lecture 3 : Mechanisms of Regulation

LD Expression of Isoenzymes .

↳ Regulation of Enzymatic Activity .inhibitors

↳ conformational changes of enzymes and EnzymaticRxns.

↳ Allostery .

↳ Modulators ( inhibitors / activators . . . )

↳ Reversible covalent modification .

4> Irreversible covalent modification .

↳ Regulation of envy me amount .

↳ Location (compartmentalization + completingof enzymes

↳ Non - specific Regulation .

Rxnls) → reaction is) .

Mishkat Ihsan

Key

Sat 10 July lecture 3 : Isoenzymes ( isozymes) .

What are isozymes ? they are enzymes that can act on the same substrates) producingthe same products) .

⇒ So, they catalyse the same rxn .

Isozymes are v. similarDifferences b/w ① They are produced by different genes← only varry slightly .

isozymes ?② They are present in different tissues . c- can be in the same tissue .

③ Regulated differently . Gene Gene Gene Gene

A B C D

how ?

④ They have different Catalytic Activity.how ?

Isozyme Isozyme Isozyme Isozyme

① ;) r /①r A ☐ c ☐

s s←

r

isozyme # I L isozyme#2 isozyme# 3

Catalyses A -30 catalyses 0-1 can catalyseMuscle stomach Embryo cancer cells

⑦ efficiently than 4efficiently than both rxns0 → A b-so efficiently .

0 activating ☐ inhibiting neither

Aerobic Us . AnaerobicMetabolism Glucose

NAD-1 ADP

← to rxns in Glycolysis .

Why change pyruvate to produce NA15→ to sustain gtycotitil result -DATP + NADH

to lactate? pathway (glycolysis) NADH < > ATP Re- carrier

while producing enough ATD V

PyruvateEnzyme if ✗ 02 if V02to keep the system goingLactate Enzyme

Dehydrogenase pyruvate

NADH dehydrogenase

Lactate TNAD' >

Acetyl C0A Aerobic MetabolismAnaerobic metabolism

C02-1HN^

CITRIC ACIDCYCLE

/ CREBS

ATP ← Oxidative NADH

phosphorylation←FADH <

>

ATP

rxn → reaction.

# → number.

In → high / increase.

b/w → between .

Mishkat Ihsan

Key

Sat 10 July lecture 3 : Lactate Dehydrogenases ( LDH )

It is not a single Enzyme it is in reality 5 different enzymes .

All LDH enzymes are tetrameric enzymes .

↳ composed of 4 polypeptides .

LDH - I

LDH enzyme can be made of :I or 2 protein subunits : ③ they all catalyse the same rxn :

Different combinations ofLDH -2

① H ( produced in high quantities in heart) .→ Hand it causes LDH -3

② M ( produced in high quantities in skeletal muscles + liver) . 5 LDH : LDH -4 oxidizedLDH -5

NAD"

NADH + H'

OHo

21-1+-125 Oo

4 Differences b/w ISOZYMES ? ↳ different primary structure due to CH} CH C Lactate -dehydrogenase CH} C C

o-

o-

4> different kinetic Lactate 21-1++25 Pyruvate

properties . NAD' NADH -11-1-1

↳ different isoelectric

point. reduced

④ different Regulation

D taffinity to lactateisozymes are highly homologues

u.g.m.w.m.n.ae#.....µ , ,, ,,,,,a,..

☐ isoemymeslfesen-in-ea.edu

① they are produced by LDHI myocardialNADT NA0H-1HT

net charge H4 Myocardiuminfraction

¥nD LDH > 1

different genes 14in heart) Lactate☐

☒ PyruvateI ' r n

oxidized

> they all <☐H2,

It} MI RBC

-

LDHB subunit③ they are

→

can catalyzecatalyze the 9At heart'

present in g reduction but pretense ②$A same r×n §.

oxidan.cn . Different

µp,

different ¥ LDH } § Hzmz Lungs - CatalyticS tissues

isozymes s ActivityE.Nucleus subunit S (Affinity)MLmuscle)

liver LDHY HIM } Kidney-

tonet charge- 6

NADH -11-1-1 NADT-(DH5

R×"LDH 7M5 Skeletal muscle Skeletal muscle ~D Lactate'

☐ Pyruvate① in muscles + +

+ liver ) liver liverdisease reduced

☐LDH 5 favors pyruvate reduction

rxn → reaction.

# → number.

4 affinity to pyruvate

4 → high / increase. ⑦

b/w → between .① affinity ( tkµ ) to S

→ low / decrease . → they prefer to catalyseS → Substrate S

.

Mishkat Ihsan

Key

4 LDH ILDH 5 ( heart TH)

( muscles + liver)Blood """

ereaq.gg,

5

3 NADT NADH + It'

NADH + It' NADT 7

7 Lactate☐

☒ Pyruvate6 oxidized

^"""" "° " ""

reduced Glucose "All It,

"

"All My" NAD-1 ADP

Why is the locationthat's why z

of LDH imp . ? ,EÉ tatiinity to lactate

Muscles can function anaerobically o

NAD" < > ATPLDHI favors lactate oxidation

-

Vbut the heart tissue Cann't .±

Pyruvate <Enzyme if ✗ Oz if ✓ 02

7

EnzymeLactateÉÉDehydrogenase

pyruvatethat's why

)L NADH dehydrogenase (LDH 5 favors pyruvate reduction Lactate TNAD" >

4 affinity to pyruvateAcetyl C0A Aerobic Metabolism 8

2 Anaerobic metabolism7 II C02-1HU producing a lot

"

anaerobic ATP in muscles finish producing some ^CITRIC ACID of energy

energy that CYCIE

quickly so another source forsustains / CREBS

ATP is needed Oxidativethe musclesATP ←

phosphorylation←^^""

FADHT10 TTTP

9r

rxn → reaction.

# → number.

In → high / increase.

b/w → between .

I → low / decrease .

Mishkat Ihsan

Key

Sat 10 July lecture 3 : Regulation of LDH

☐ I KM for pyruvate + is not inhibitedLDH 5 My & by pyruvate

( muscles + liver) 4 affinity for pyruvate4) always 4

active pyruvate reduction

even at 4 levels of pyruvatewhy ?

to ensure that pyruvate is always funneled to anaerobic metabolism.

→ ⑥ Km for lactate + 4 Km for pyruvateLDH 1 Iv( heart TH ) 4 affinity for lactate + is inhibited by 9 pyruvate .

4 Ilactate oxidation . if heart muscle produces 4 pyruvate

①Rxn Stops①

allowing lactate to be present inother tissues .

rxn → reaction.

In → high / increase.

b/w → between .

I → low / decrease