1.

MOVIE HIGHLIGHT
a) Introduction

(source: https://www.imdb.com/title/tt0104756/ )

Main Cast:

Nick Nolte as Augusto Odone

Susan Sarandon as Michaela Odone
Zack O'Malley Greenburg as Lorenzo Odone

Background:

Lorenzo's Oil (1992) is an American drama which was directed by George

Miller. It is based on the real-life experiences of Augusto and Michaela
Odone, parents who developed Lorenzo's oil while looking for a treatment for
their son Lorenzo's adrenoleukodystrophy (ALD).

b) Story Summary

Lorenzo Odone is a son of a married couple named Nick Nolte and

Susan Saradon. In 1983, Lorenzo had followed his parents to live on Comoros
Island, Africa. He was a cheerful and brave child. Moreover, he has a loved
person named Omouri who is very concerned about Lorenzo.

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 Three months after that, Lorenzo returned with his parents to
Washington D.C., USA. When he was at school, one of Lorenzo's teachers had
a strange feeling with Lorenzo's behavior which could not control his
emotions. Because of this condition, Lorenzo was advised to be transferred to
a special education class, Individual Disability Placement (IDP).

On Christmas season, Lorenzo had fallen from a chair because he

wanted to take ornaments from the Christmas tree. Not long after that, there
was an incident where Lorenzo was listening to a song with a very loud noise.
This condition caused his parents to worry so much, they took Lorenzo to
Washington Children's Hospital on the Easter weekend of 1984. Several
medical tests were carried out by doctors to diagnose Lorenzo's illness. The
results from the doctor showed that Lorenzo had a disease from
Leukodystrophies (family diseases) called Adrenoleukodystrophy (ALD). Dr.
Judalon said that boys with ALD would die within two years.

After knowing the results of the doctor's diagnosis, Lorenzo's parents

met Professor Gus Nikolais. The professor explains that ALD is a disease

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inherited from a mother and he offers Lorenzo as material for observation and
research for all doctors. One of the ways that the Professor suggests to slow
down the ALD is by limiting the intake of foods such as peanut butter, red
meat, cheese, unpilled fruit, olive oil, and spinach. At the age of 6 Lorenzo
showed an increase in fatty acids in his brain, causing more concern to his
parents.

On July 1984, Boston, Lorenzo is shown to all the doctors in the

conference room to find the best solution for him. A doctor explained to all
doctors that Lorenzo has hemianopia with transient horizontal nystagmus and
has evidence of occipital-lobe involvement.

Lorenzo's parents were invited to a parents' association where they had

children with ALD and this was where a dispute occurred with the chief
organizer, Lorenzo's parents were very concerned about the doctor's solution
which didn't make sense by limiting intake and this was what Lorenzo's
mother wanted to discuss about dietary intake issues at the conference.

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 On August 1984, Lorenzo's parents tried to find a way out for
Lorenzo's health. Lorenzo's father said that in the human body there are two
sources of fatty acids, from food intake and the process of biosynthesis in the
body. In Lorenzo's case, the enzyme to break down the fatty acids doesn't
work normally, the saturated C24 and C26 rise four times from the normal
level. At that time, Lorenzo's parents were confused, when they continued to
reduce the food intake, there was an excess accumulation of fatty acids.

Lorenzo's mother continues to study to find the cause of the problem

and she has an explanation for the paradox. She said that Polish rats with a
fatty-acid storage disease have the same thing as humans, when they stop
eating food, more biosynthesis production will occur as a result of not having
food intake. She also conveyed this to the Professor and discussed it at the
symposium to accelerate the exchange of information on November 10th
1984. From the results of the symposium it was stated that there was one
chemical compound, namely triglyceride from oleic acid, which could help
with ALD.

Oleic acid was finally obtained from the Protochem company,

Cleveland. This oleic acid was consumed by Lorenzo for months, there was a
decrease in fatty acid in Lorenzo. Lorenzo's parents wanted to tell other
parents that oleic acid could help a person with ALD. There was great
opposition from the conference chief, but the will of Lorenzo's parents was
still very strong. There was a point where Lorenzo showed no progress, some
of the effects of ALD appeared.

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 Lorenzo's parents then continued self-study again about Lorenzo's
illness and stated that Erucic acid could help Lorenzo get better. Erucic acid is
very hard to get by, luckily Croda Chemicals had a researcher who wanted to
help make an Erucic acid.

From the consumption of Erucic acid, it shows very significant

progress. Lorenzo is getting better, but his parents are still learning about ALD
and the best solution for Lorenzo. Day by day Lorenzo is getting better, he can
express and respond to words spoken by his family through eye movements.

2. BIOCHEMISTRY KNOWLEDGE
a) Disease

Adrenoleukodystrophy (ALD) is a genetic disorder linked to the X

chromosome due to a protein carrier that fails to function properly. ALD
sufferers' bodies produce fatty acids that accumulate in nerve cells and damage
the lining of the motor system. With a ratio of 1 in 20,000 boys, ALD illness is
more prevalent in boys. Boys between the ages of 4 and 8 are typically
affected by this illness, and those who are diagnosed with ALD have a two-
year survival rate [1].
Brain function will decrease as the myelin sheath is gradually stripped
by this disease from the brain's nerve cells. Myelin functions as a regulator of
the way humans think and controls the work of the body's muscles. Without
this sheath, the nerves cannot work. In other words, the nerves will stop
sending signals to the muscles and other supporting elements of the central
nervous system about what to do [5].
Some individuals affected by ALD have adrenal insufficiency,
meaning underproduction of certain hormones (adrenaline and cortisol, for
example) that causes abnormalities in blood pressure, heart rate, sexual

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 development, and reproduction [1]. Some of the ALD patients experience a
number of serious neurological problems that can affect mental function [5].

b) Enzyme (Metabolic Pathway)

Peroxisomal beta-oxidation pathway adalah sistem yang menguraikan

very ling chain fatty acids, which accumlate in plasma and tsissues in X-linked
ALD. Pathway ini terdidi dari of acyl-CoA oxidase, the bifunctional enoyl-
CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and beta-ketothiolase [3].

(Source: https://www.researchgate.net/figure/Comparison-of-peroxisomal-and-mitochondrial-fatty-acid-b-oxidation-pathways-As_fig1_272519391)

Rather than fully destroying fatty acids, peroxisomal beta-oxidation

shortens their chain by initiating a small number of beta-oxidation cycles.
Very long chain (> C20) fatty acids, dicarboxylic fatty acids, 2-methyl-
branched fatty acids, prostaglandins, leukotrienes, the carboxyl side chains of
various xenobiotics, and the intermediate bile acids dihydroxycoprostanic
acids and trihydroxycoprostanic acids are all beta-oxidized by peroxisomes
[3].

c) Fatty Acid
i. Oleic Acid

Oleic acid is an omega-9 fatty acid that can be found naturally in fats
and oils, both animal and vegetable. This acid is included in monounsaturated
fatty acids which are classified as good or healthy fats. Oleic acid is generally
odorless and colorless [9].
The advantages of oleic acid are necessary for the body's cells to
remain healthy and functioning. As a result, cells in the body can respond to
hormones, transport minerals, and fight off viruses. Oleic acid is employed in

6
the manufacture of several vital substances in the body as well as serving as
the primary energy source for cells.

(Source:https://pubchem.ncbi.nlm.nih.gov/compound/Oleic-acid)

Oleic acid has a double bond at C-9 that has Z (cis) stereochemistry
with a molecular weight of 282.5 g/mp. This type of fatty acid is also known
as cis-9-Octadecenoic acid, oleate, and (Z)-Octadec-9-enoic acid. Its boiling
point and melting point are 286 oC at 100 mgHg and 16.3 oC, respectively [7].

ii. Erucic Acid

Erucic Acid is a monounsaturated very long-chain fatty acid with a

22-carbon backbone and one double bond that originates in the 9th position
from the methyl end and is in the cis-conformation. Erucic acid is more
easily biodegradable than some, it shares many of the same applications as
mineral oils. For use in oil paints, it has a restricted capacity to polymerize
and dry. Like other fatty acids, it can be utilized as a precursor to biodiesel
fuel and transformed into lubricants or surfactants [4].

(Source: https://pubchem.ncbi.nlm.nih.gov/compound/5281116#section=2D-Structure)

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 In medical used, dietary erucic acid therapy is efficient in bringing
plasma C26 levels in ALD patients back to normal and may stop progressive
demyelination in certain boys who are only mildly afflicted.

d) Lipids

Very long-chain fatty acids (VLCFA) is type of lipids that involved in

the ALD diseases. It is marked by building up in the brain, testis, adrenal
glands, and akin cells. The protective myelin coating that surrounds nerve
cells, which is essential for brain function, is destroyed when VLCFAs build
up [1].
Sphingolipid are a class of lipids consisting of an 18-carbon amino-
alcohol backbone, sphingosine. It is a structural component of cell membranes
and is the second type of lipid, which is a structural component of cell
membranes, especially brain tissue and nerve cells. It is an amphipathic
containing, a polar head group and two non-polar fatty acid tails [6].
Because of their capacity to form tiny domains in the plasma
membrane, sphingolipids play a crucial role in the formation of the brain.
They also play a role in neural differentiation, synaptic transmission at
neuronal-glial junctions, and myelin stability. As a result, different
sphingolipid metabolic abnormalities can cause the plasma membrane to be
rearranged, which can result in a variety of neurological diseases.
There are some classes of sphingolipids but ceramides are the main
factor in ALD diseases. Ceramide is a long-chain fatty acid amide derivative
of sphingosine. In other words, it combines a fatty acid with sphingosine
alcohol. Ceramide derivatives are created by joining an OH group to C1 [2].

(Source:https://www.researchgate.net/figure/Chemical-structure-of-ceramide-species-ceramide-phytoceramide-and-dihydroceramide_fig1_51590557)

Ceramide forms derivatives such as sulfatides, globosides,

glucosylceramide, sphingomyelin, and gangliosides when it interacts with
other molecules. These substances are essential for the growth of the nervous
system and the brain [8].

3. FEEDBACK

From this film I learned that in the body every individual has different
characteristics. The disease that Lorenzo is suffering from has opened the eyes
of the world of health to remain concerned about rare diseases that can appear
at uncertain times. Lorenzo's parents who continue to try to heal their children
also teach every human being to continue not to give up on achieving goals
despite the many obstacles that need to be overcome. Lastly, from this film I
am even more interested in studying biochemistry because in this universe
there are interesting things and need more attention to find answers and
solutions.

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REFERENCE
[1] Adrenoleukodystrophynews. www.adrenoleukodystrophynews. Accessed
th
January 6 , 2023.
[2] Asha Kumari. 2018. Chapter 13 - Ceramide Structure and Derivatives. Sweet
Biochemistry. Pages 59-61. https://doi.org/10.1016/B978-0-12-814453-4.00013-
3.
[3] Chen WW, Watkins PA, Osumi T, Hashimoto T, Moser HW. 1987. Peroxisomal
beta-oxidation enzyme proteins in adrenoleukodystrophy: distinction between X-
linked adrenoleukodystrophy and neonatal adrenoleukodystrophy. Proc Natl
Acad Sci U S A. 84(5):1425-8. doi: 10.1073/pnas.84.5.1425. PMID: 3469675;
PMCID: PMC304443.
[4] Efsa.www.efsa.europa.eu/en/press/news/161109#:~:text=Erucic%20acid%20is
%20a%20monounsaturated,home%20cooking%20in%20some%20countries.
Accessed Janury 5th, 2023.
[5] Hellosehat.https://hellosehat.com/saraf/saraf-lainnya/adrenoleukodystrophy-ald-
gangguan-otak-turunan/. Accessed January 2nd, 2023.
[6] Hussain, Ghulam et al., 2019. “Role of Cholesterol and Sphingolipids in Brain
Development and Neurological Diseases”. Lipids in Health and Disease.
18(26). https://doi.org/10.1186/s12944-019-0965-z.
[7] Pubchem.https://pubchem.ncbi.nlm.nih.gov/compound/Oleic-acid. Accessed
nd
January 2 , 2023.
[8] Pubchem.www.pubchem.ncbi.nlm.nih.gov/compound/74945544. Accessed
th
January 5 , 2023.
[9] SehatQ.www.sehatq.com/artikel/segudang-manfaat-asam-oleat-bagi-kesehatan-
tubuh-anda. Accessed January 5th, 2023.