Biochemistry - Lecture 20 Mixed Oxidases

Front 1

What are 4 classes of oxidoreductases?

Back 1

1 - oxygenase
2 - dehydrogenase
3 - oxidases
4 - hydroperoxidases

Front 2

What are 2 types of oxygenases?

Back 2

1 - monooxygenase - R-H + O2 + ZH2= ROH + H2O
2 - dioxygenase - R + O2= RO2

Front 3

What do oxidases do?

Back 3

They remove hydrogen using oxygen as hydrogen acceptor. Products are water or hydrogen peroxide.

R-H + O2 = R + H2O2

Front 4

What do hydrolases do?

Back 4

They transfer hydrogen from one substrate to another.

Front 5

What do hydroperoxidases do?

Back 5

They use organic peroxides or hydrogen peroxides as substrates.

Front 6

What are two types of hydroperoxidases and what do they do?

Back 6

1 - peroxidase - use peroxide
2 - catalse - breaks down hydrogen peroxide.

Front 7

What 7 reactions are monoxygenases involved with?

Back 7

1- CYTOCHROME P450
2 - Tyrosin synthesis
3 - Serotonin synthesis
4 - Catecholamine synthesis
5 - Cholesterol synthesis
6 - Vitamin D synthesis
7 - Nitric Oxide

Front 8

What 3 reactions are dioxygenases involved with?

Back 8

1 - PROSTAGLANDIN SYNTHESIS
2 - Tyrosine degradation
3 - Collagen modification
4 - Retinal formation

Cosubstrate is asorbic Acid - Vitamin C

Front 9

Where does Cytochrome p450 reside?
What are some of its characteristics?

Back 9

Endoplasmic Reticulum and mitochondria in liver.
Has a heme in the center.

Front 10

What functions does Cytochrome p450 have?

Back 10

1. Hydroxylation, epoxidation, modification of hydrophobic drugs for detoxification.

2. synthesis of steriod hormones

3. synthesis of bile acids

Front 11

What is the pathway of Cytochrome p450?

Back 11

Check powerpoint

Front 12

How is Cytochrome p450 used in the synthesis of Steroid hormones?

Back 12

Cholesterol ----> Pregnenolone ---> Glucocorticoids, mineral corticoids, androgens

Front 13

How does CP450 modify compounds foreign to the body?

Back 13

via hydroxylation

-example of ibuprofen--occurs in the ER of the Liver and Small Intestine. Makes ibuprofen much more soluble, excrete it much quicker.

Front 14

Explain the pathway of Acetaminophen toxicity (overdose) by CP450.

Back 14

Acetameniphon (tylenol)-->n-acetyl p benzoquinione----> product

*N acetyl benzo is highly reactive and is involved in modification of thiol containing compounds, leads to liver failure.

* notice a 7-10g drop of Gluthatione in liver cells of adults bc it's used to try to decrease the toxicity.

Front 15

Explain pathway of benzopyrene and CP450 and how it is bad for you.

Back 15

benzopyrene x CP450--> benzopyrene epoxide x epoxide hyrdolase--> benxopyrene diol x CP450 -->benzopyrene diol epoxide.

The product is highly carcinogenic.
This comes from burning organic goods like wood, etc.

Front 16

Explain Tyrosine Synthesis

What disease is associated with this?

Back 16

Phenylalanine is converted to tyrosine with monooxygenase.

Mutation in phenyl. oxygenase leads to phenylketonuria because phenylalaine is converted to phenylpruvate which converts to phenylketone.

phenylketonuria - mental retardation

Front 17

Explain Serotinin Synthesis

What disease is associated with this?

Back 17

Typtophan converted to serotonin.

Lack of serotonin causes depression.

Front 18

Catecholamine synthesis

Back 18

Tyrosine--->DOPA (via monooxygenase) --->dopamine --->noepinephrine (monooxygenase)---->epinephrine


Stress hormone, adrenaline rush.
High stress causes Increase in HR, increase glucose, blood pressure

Front 19

Cholesterol synthesis

What enzyme does Lipitor act on?

Back 19

FA-->Acetyl Coa--->Hmg Coa--->Melvonate --->SQUALENE (monooxygenase) --->cholesterol

Lipitor acts on HMG CoA reducatase which converts Hmg Coa to Melvonate.

Front 20

What are the 2 enyzmes used in Vitamin D synthesis? Where are they used?

What disease are associated with mutations in vitamin D synthesis?

Back 20

Liver - 25 hydroxylase (monooxygenase)

Kidney - 1 alpha hydroxylase (monooxygenase)

rickets and osteomalacia due to deficiency in vitamin D

Front 21

What are three types of Nitric Oxide syntheses?

Back 21

They are all monooxygenase

nNOS - neuronal - signaling
eNOS - endothelium - vasodilation
INOS - inducible - immunity

Front 22

What are two parts of the dioxygenase enzyme in prostaglandin synthesis? What drugs inhibit it?

Back 22

Prostaglandin Synthase (COX)

COX I - mucosal defense
COX ll - upregulated at sight of inflammation, causing pain and fever

NSAIDS - target COX ll.
-ibuprofen, aspirin, celebrex, vioxx, bextra

acetaminophen - Cox lll?

Front 23

What disease is associated with tyrosine degradation? what enzyme is affected?

Back 23

x5 - alkaptournia

mutation in enzyme homogentiase diooxygenase

Front 24

What enzyme is used in Collagen modification?
What disease is associated with it

Back 24

4 proyl hydroxylase

Scurvy - lack of asorbic acid which is a cofactor of 4-pyorl hydroxylase

Front 25

What disease is associated with retinal formation? defect in monooxygenase or dioxygenase?

Back 25

Vitamin A deficiency causes night blindness

mutation in dioxygenase

Front 26

Why is drinking so bad for you? What group of enzymes is used that causes harmful effects to the body?

Back 26

Microsomal ethanol oxidizing system is used and it creates ROS that damages liver.

CYP2E1

Front 27

What cofactor does dompamine beta hydroxyls cathecolamine synthesis need?

Back 27

vitamin c

Front 28

explain the atp synthesis by binding change mechanism

Back 28

O-L-T-O method to making atp

O-form: ATP is released. ADP and Pi are loosely bound.

L -form: ADP and Pi are tightly bound. Need this site to be filled by adp and pi in order for atp to be released.

t form: adp and pi are in equilibrium with ATP. ATP is only released when t goes to o form. ******TO GO FROM T TO O FORM, YOU NEED ENERGY FROM THE PROTON GRADIENT( ENERGETICALLY UPHILL).