Adrenoleukodystrophy an Xlinked, sexlinked,

1
Adrenoleukodystrophy an X-linked,
sex-linked, recessive, genetic disorder
Unaffected male
Affected male
Unaffected female
Affected female
Mr. Murphy
Mrs. Murphy
XAXa
XAY
Canise
Mariah
Michaela
Diedre
Augusto
XAX?
XAXA
XAXa
XAXa
XAXa
XAY
XAY
XAY
Lorenzo
Christina
Francesco
XAX?
XAX?
XAX?
XaY
XAY
XAY
2
Augusto Adones Kitchen Sink Analogy for
Long-Chain Saturated Fats
Tap Diet as source of long-chain
saturated fatty acids
Sink Lorenzos body
Drain enzyme which digests excess long-chain
saturated fatty acids
3
Augusto Adones Kitchen Sink Analogy for
Long-Chain Saturated Fats
Tap Diet as source of long-chain
saturated fatty acids
Sink Lorenzos body
Plugged drain missing enzyme
in boys with ALD
Drain enzyme which digests excess long-chain
saturated fatty acids
4
Augusto Adones Kitchen Sink Analogy for
Long-Chain Saturated Fats
Tap Diet as source of long-chain
saturated fatty acids
Rising water level in sink Rising level
of long-chain saturated fats in blood from
diet, which destroy myelin
Sink Lorenzos body
Plugged drain missing enzyme
in boys with ALD
Drain enzyme which digests excess long-chain
saturated fatty acids
5
Augusto Adones Kitchen Sink Analogy for
Long-Chain Saturated Fats
Tap Diet as source of long-chain
saturated fatty acids
Tap turned off therapy by diet, remove
long-chain saturated fats from diet
Rising water level in sink Rising level
of long-chain saturated fats in blood from
diet, which destroy myelin
Sink Lorenzos body
Plugged drain missing enzyme
in boys with ALD
Drain enzyme which digests excess long-chain
saturated fatty acids
6
Augusto Adones Kitchen Sink Analogy for
Long-Chain Saturated Fats
Tap turned on increased biosynthesis
maintaining high levels of long-chain saturated
fats in blood
Tap Diet as source of long-chain
saturated fatty acids
Tap turned off therapy by diet, remove
long-chain saturated fats from diet
Rising water level in sink Rising level
of long-chain saturated fats in blood from
diet, which dissolve myelin
Sink Lorenzos body
Plugged drain missing enzyme
in boys with ALD
Drain enzyme which digests excess long-chain
saturated fatty acids
7
Long-Chain Saturated Fatty Acids
H H H H H H H H H H
H H H H H H H O I
I I I I I I I I
I I I I I I I I
II HCCCCCCCCCCCCCCCCCCO
I I I I I I I
I I I I I I I I
I I H H H H H H H
H H H H H H H H H H
H
Saturated C18H36O2 Octadecanoic acid, or stearic
acid
H H H H H H H H H H
H H H H H H H H H H H
O I I I I I I
I I I I I I I I
I I I I I I I
II HCCCCCCCCCCCCCCCCCCCCCCO
I I I I I I
I I I I I I I I
I I I I I I I
H H H H H H H H H H
H H H H H H H H H H H
H
Saturated C22H44O2 Docosanoic acid, or behenic
acid
H H H H H H H H H H
H H H H H H H H H H H
H H O I I I I I
I I I I I I I I
I I I I I I I I
I I II HCCCCCCCCCCCCCCC
CCCCCCCCCO I I I
I I I I I I I I
I I I I I I I I
I I I I H H H H
H H H H H H H H H H H
H H H H H H H H
H
Saturated C24H48O2 Tetracosanoic acid, or
lignoceric acid
8
Long-Chain Monounsaturated Fatty Acids
H H H H H H H O I
I I I I I I
II CCCCCCCCO I I I
I I I I H H H H H H
H H
H H H H H H H H
I I I I I I I I
HCCCCCCCC I I
I I I I I I H H
H H H H H H

C
C

H
H
Monounsaturated C18H34O2 cis-9-Octadecenoic acid,
or oleic acid
9
Long-Chain Monounsaturated Fatty Acids
Monounsaturated C22 C42O2 cis-13-Docosenoic acid,
or erucic acid
10
Long-Chain Monounsaturated Fatty Acids
H H H H H H H H H H
H H H O I I I I I
I I I I I I I I
II CCCCCCCCCCCCCCO I
I I I I I I I I
I I I I H H H H H
H H H H H H H H
H
H H H H H H H H
I I I I I I I I
HCCCCCCCC I I
I I I I I I H H
H H H H H H

C
C

H
H
Monounsaturated C24 C46O2 cis-15-Tetracosenoic
acid, or nervonic acid
11
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
CH3(CH2)22COOH
nervonic acid
lignoceric acid
12
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
CH3(CH2)22COOH
nervonic acid
lignoceric acid
13
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
CH3(CH2)22COOH
nervonic acid
lignoceric acid
14
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
CH3(CH2)22COOH
nervonic acid
lignoceric acid
15
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
CH3(CH2)22COOH
nervonic acid
lignoceric acid
16
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
17
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
Enzyme
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
18
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
CH3(CH2)20COOH
Enzyme
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
19
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
20
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
21
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
CH3(CH2)22COOH
nervonic acid
lignoceric acid
22
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
Enzyme
CH3(CH2)22COOH
nervonic acid
lignoceric acid
23
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Biosynthesis
Enzyme
CH3(CH2)22COOH
nervonic acid
lignoceric acid
24
Competitive Inhibition inhibiting biosynthesis
of long-chain saturated fatty acids by increasing
biosynthesis of long-chain monounsaturated fatty
acids
CH3(CH2)16COOH
oleic acid
stearic acid
Competitive Inhibition
Enzyme
CH3(CH2)20COOH
erucic acid
behenic acid
Diet therapy
Competitive Inhibition
Enzyme
CH3(CH2)22COOH
nervonic acid
lignoceric acid