Adrenoleukodystrophy – an X-linked, sex-linked,recessive, genetic disorder

Mr. Murphy Mrs. Murphy

Canise Mariah Michaela DiedreAugusto

Lorenzo Christina Francesco

XAX?

XAX?

XAX?

XAXA

XAXaXAY

XAX?

XAXaXAXaXAXa XAYXAY XAY

XaYXAY XAY

Affected femaleUnaffected female

Unaffected maleAffected male

Augusto Adone’s Kitchen Sink Analogyfor Long-Chain Saturated Fats

Sink = Lorenzo’s body

Tap = Diet as source of long-chain saturated fatty acids

Drain = enzyme which digests excess long-chain saturated fatty acids

Augusto Adone’s Kitchen Sink Analogyfor Long-Chain Saturated Fats

Sink = Lorenzo’s body

Tap = Diet as source of long-chain saturated fatty acids

Drain = enzyme which digests excess long-chain saturated fatty acids

Plugged drain = missing enzyme in boys with ALD

Augusto Adone’s Kitchen Sink Analogyfor Long-Chain Saturated Fats

Sink = Lorenzo’s body

Tap = Diet as source of long-chain saturated fatty acids

Drain = enzyme which digests excess long-chain saturated fatty acids

Plugged drain = missing enzyme in boys with ALD

Rising water level in sink = Rising level oflong-chain saturatedfats in blood from diet,which destroy myelin

Augusto Adone’s Kitchen Sink Analogyfor Long-Chain Saturated Fats

Sink = Lorenzo’s body

Tap = Diet as source of long-chain saturated fatty acids

Drain = enzyme which digests excess long-chain saturated fatty acids

Plugged drain = missing enzyme in boys with ALD

Rising water level in sink = Rising level oflong-chain saturatedfats in blood from diet,which destroy myelin

Tap turned off = therapyby diet, remove long-chainsaturated fats from diet

Augusto Adone’s Kitchen Sink Analogyfor Long-Chain Saturated Fats

Sink = Lorenzo’s body

Tap = Diet as source of long-chain saturated fatty acids

Drain = enzyme which digests excess long-chain saturated fatty acids

Plugged drain = missing enzyme in boys with ALD

Rising water level in sink = Rising level oflong-chain saturatedfats in blood from diet,which dissolve myelin

Tap turned off = therapyby diet, remove long-chainsaturated fats from diet

Tap turned on = increasedbiosynthesis maintaininghigh levels of long-chainsaturated fats in blood

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 IIH—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—O 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

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 IIH—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—O 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 IIH—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—C—O 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

Long-Chain Saturated Fatty Acids

Monounsaturated C18H34O2

cis-9-Octadecenoic acid, or oleic acid

H H H H H H H H

I I I I I I I I

H—C—

C—C—

C—C—

C—C—

C—

I I I I I I I I

H H H H H H H H

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H H

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H O

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C—C—

C—C—

C—O

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H H

H

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C C——

Long-Chain Monounsaturated Fatty Acids

H H H H H H H H

I I I I I I I I

H—C—

C—C—

C—C—

C—C—

C—

I I I I I I I I

H H H H H H H H

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C—C—

C—O

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C C——

Monounsaturated C22 C42O2

cis-13-Docosenoic acid, or erucic acid

Long-Chain Monounsaturated Fatty Acids

Monounsaturated C24 C46O2

cis-15-Tetracosenoic acid, or nervonic acid

H H H H H H H H

I I I I I I I I

H—C—

C—C—

C—C—

C—C—

C—

I I I I I I I I

H H H H H H H H

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C C——

Long-Chain Monounsaturated Fatty Acids

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Diet therapy

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Diet therapy

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Diet therapy

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

Biosynthesis

Diet therapy

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

CC

Enzyme

Diet therapy

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

CC

Diet therapy

Enzyme

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

Diet therapy

Enzyme

CompetitiveInhibition

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

Diet therapy

Enzyme

CompetitiveInhibition

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

Diet therapy

Enzyme

CompetitiveInhibition

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

C

C Diet therapy

Enzyme

Enzyme

CompetitiveInhibition

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

C

C Diet therapy

Enzyme

Enzyme

CompetitiveInhibition

Biosynthesis

Competitive Inhibition – inhibiting biosynthesis of long-chainsaturated fatty acids by increasing biosynthesis of long-chainmonounsaturated fatty acids

CH3(CH2)22COOH

CH3(CH2)20COOH

CH3(CH2)16COOH

CH3(CH2)7CH CH(CH2)13COOH——

CH3(CH2)7CH CH(CH2)7COOH——

CH3(CH2)7CH CH(CH2)11COOH——

oleic acid

nervonic acid

erucic acid

stearic acid

lignoceric acid

behenic acid

C

C

C

C Diet therapy

Enzyme

Enzyme

CompetitiveInhibition

CompetitiveInhibition