PRINCIPLES IN

BIOCHEMISTRY
SBK3013
2015/2016

Aisyah Sahira bt Abdul Rahim

D20141066916
Nur Syaliyana
Abu Samah:
GROUPbtMEMBERS
D20141066904
Nor
Athirah
bt
Zalbador
D20141066901
Ainul
Izzatti
bt
Zulkifli
D20141066907
Nur
Insyirah
bt
Tokijoh
D20141066923
Nurul
Akma
bt
Yaziz
D20141066900
Nurul Jannah bt Md Yassin
D20141066913

CARNITINE
DEFICIENCY

CASE:
A teenage boy was brought to a hospital as he complaints
that he always get too tired when asked to participate in
the any of school activities. The doctor found muscle
weakness in the boys arms and legs. From the muscle
biopsy, the lab pathologist found that greatly elevated
amount of triglycerides esterified with primary long
fatty acid chain. They also found significant presence of
lipid vacuoles in the muscle biopsy. What causes this
symptoms?

Focus of this case

1.What is the effect of low carnitine?
2.How people with the disorder metabolize muscle
glycogen aerobically?

Carnitine ?
Carnitine is the quaternary ammonium compound biosynthesized from the
amino acids lysine and methionine.

Carnitine produced by ?
Liver and kidneys, but mostly located in the
voluntary muscle and cardiac muscles.

Carnitine deficiency?
Do you know what is carnitine deficiency?
A metabolic state in which carnitine concentrations in plasma and tissues
are less than the levels required for normal function of the organism.
This is a metabolic muscle disease that interferes with the processing of
food such as fats for energy production.
Carnitine deficiency results from inadequate intake of or inability to
metabolize the long chain of amino acids.

Function of Carnitine
The amino acid carnitine is required for the transport of long-chain fatty
acyl coenzyme A (CoA) esters from the intermembraneous space in the
mitochondria into mitochondrial matrix , where they are oxidized for
produce energy by breaking down the lipids.
Transports toxic or waste compounds out of cellular organelle to prevent
accumulation.
Convert fat into energy - by transports of fatty acids into the mitochondria

http://www.asbmb.org/asbmbtoday/asbmbtoday_article.aspx?id=8742

Types of carnitine ?
1. Primary carnitine deficiency : Genetic disorder of the cellular carnitine
where the transport system that usually with symptoms of cardiomyopathy,
skeletal muscle weakness and hypoglycemia.
2. Secondary carnitine deficiency : Shows in the certain disorder such as
chronic renal failure or under certain condition which using certain antibiotic.
It can reduce the carnitine absorption and increase its excretion.

Primary Carnitine Deficiency:

Prevent the body from using certain fats for energy .
Appear during infancy or early childhood:
- Brain disfunction
- Weak and enlarged heart (cardiomyopathy)
- Muscle weakness
- Low blood sugar (hypoglycemia)
Some people are asymptomatic : does not show any signs or signals.

How primary carnitine occur ?

Low level of carnitine level in blood
Gene mutation
The gene provide information for making protein that transports carnitine
into cells
This mutation can affect carnitine transport by impairing maturation of
transporters to the plasma membrane
Result of mutation causes an absent/dysfunctional of the protein
Shortage (deficiency) of carnitine within cells
Without carnitine, fatty acids cannot enter mitochondria and be used to
make energy

Gene Mutation ?
Mutation :
- SLC22A5 gene : give instruction to make OCTN2 protein to transport
the carnitine.
- Result of the mutation : an absent or dysfunction of OCTN2 proteins
- Create a premature stop signal in the instructions for making the
OCTN2 protein, resulting in an abnormally short, nonfunctional
protein. Other mutations change single protein building blocks
(amino acids) in the OCTN2 protein.

http://ghr.nlm.nih.gov/gene/SLC22A5

Secondary Carnitine Deficiency:

May present with crises consisting of hypoglycemia, ketoacidosis, and
hyperammonemia.
Also may present with abnormal fatigability and lactic acidosis associated with
exertion. These children also may present with encephalopathy and/or lipid
storage myopathy and carnitine depletion.
Carnitine deficiency has been observed in children with urea cycle defects, and
it may exacerbate episodes of hyperammonemia.
* excess of a particular protein building block (amino acid), called methionine, in the blood

Primary Carnitine vs Secondary Carnitine

PRIMARY
CARNITINE

SECONDARY
CARNITINE

Rare congenital
deficiency

Decreased
carnitine
synthesis due to
liver disease

Carnitine
palmitoly
transferase
system
- Prevents
renal
absorption
of
carnitine
- Faulty
transporte
r prevents

Severely
restricted
vegetarian diet

Carnitine Transport Pathway:

Once the fatty acids accumulate in the blood, coenzymeA (CoA) attaches and activates the
fatty acids, bringing them into the cells cytosol.
A carnitine molecule then attaches, which allows the transporting receptor, carnitine-palmitoyltransferase 1 (CPT1), to recognize and transport the fatty acid across the outer mitochondrial
membrane into the intermembrane space.
Then, a carnitine-specific transfer enzyme in the inner mitochondrial membrane brings the fatty
acid into the mitochondrion for breakdown by carnitine-palmitoyl-transferase 2 (CPT2), and the
carnitine molecule is transferred back to the cytosol to shuttle more fatty acids.

Carnitine Transport Pathway :

What would happen for Fatty

Acid that not enter the
mitochondrion cells ?

What is the causes ?

Inadequate intake of nutrition due to fad diet or long term TPN
*TPN is stand for Total Parental Nutrition which is a method of feeding that bypasses the
gastrointestinal tract. It is used when a person cannot receive food or drink through his/her
mouth.

Excess loss of carnitine due to diarrhea, diuresis and hemodialysis.

Decrease muscle carnitine level due to mitochondrial impairment (due to
the use of zidovudine).
Inability to metabolize carnitine due to enzyme deficiency.(carnitine
palmitoyltransferase disease)

Symptoms carnitine
deficiency

1. Severe brain dysfunction (encephalopathy)

2. Fatigue
3. Lipid storage myopathy
4. Hyperammonia (metabolic disturbance by excess of ammonia in blood)
5. Hypoglycemia (low blood sugar)
6. Vomitting
7. Fatty liver
8. Muscle weakness

Treatment
Better diagnosis to allow for earlier identification of at-risk individuals and
earlier treatment
Continued examination of the role of exercise and diet in metabolic
diseases
Development of enzyme replacement therapies
Development of gene therapies.
Avoidance of fasting and strenuous exercise

1. L-carnitine

The main treatment for CTD is lifelong use of L-carnitine. This is a safe and
natural substance that helps body cells make energy. It also helps the
body get rid of harmful wastes. L-carnitine can reverse the heart
problems and muscle weakness that happen in children with CTD.
Your doctor will decide whether or not your child needs L-carnitine. Unless
you are advised otherwise, use only L-carnitine prescribed by your doctor.
Do not use L-carnitine without checking with your doctor.

2. Avoid going a long time without food

Infants and young children with CTD need to eat frequently to prevent a
metabolic crisis. Your metabolic doctor will tell you how often your child
needs to be fed. In general, it is often suggested that infants be fed every
four to six hours. Some babies need to eat even more frequently than
this. It is important that infants be fed during the night. They may need to
be woken up to eat if they do not wake up on their own.

Your metabolic doctor and dietician will give you an appropriate feeding
plan for your infant. Your doctor will also give you a sick day plan tailored
to your childs needs for you to follow during illnesses or other times
when your child will not eat.
Your metabolic doctor will continue to advise you on how often your child
should eat as he or she gets older. When they are well, many teens and
adults with CTD can go without food for up to 12 hours without problems.
The other treatments usually need to be continued throughout life.

3. Diet
Sometimes, in addition to L-carnitine treatment, a low-fat, high carbohydrate food plan is
recommended. Any diet changes should be made under the guidance of a dietitian familiar with
CTD. Ask your doctor whether your child needs to have any changes in his or her diet.
4. If your baby has CTD, call your doctor at the start of any illness
Always call your healthcare provider when your baby has any of the following:
poor appetite
low energy or excessive sleepiness
vomiting
diarrhea
an infection
a fever
persistent muscle pain or weakness

Are there health risks from too

much carnitine?
supposedly 3g/day

carnitine supplement can cause nausea, vomiting, abdominal cramps,

diarrhea
rarer side effects include muscle weakness in uremic patients and seizures
in those with seizure disorders
may increase the risk of cardiovascular disease
more pronounced effect to those people who likes meats than vegetarians

How people with the disorder

metabolize muscle glycogen
aerobically?
Small energy demands do not initiate glycogenolysis

Lightly loaded muscles manage to cover their energy needs through oxidation of
circulating glucose and fatty acids.
However, increasing work loads demands more powerful contractions and ATP
utilization. This increases the rate of glycogen breakdown to cover these needs.

CONCLUSION FOR THE CASE

For our patient, we are sure that he suffered Primary Carnitine Deficiency.
From the muscle biopsy, the lab pathologist found that greatly elevated
amount of triglycerides esterified with primary long fatty acid chain.
A person with primary carnitine deficiency has very low levels of carnitine in
the blood due to a faulty carnitine transporter which prevents carnitine from
getting into the cells where it is needed. Thats why, a boy felt tiredness during
activities.

TEAM RESPONSIBILITY
NAME

RESPONSIBILI
TY

AISYAH
SAHIRA BINTI
ABDUL RAHIM

HOW PRIMARY
CARNITINE
OCCUR,
SYMPTOMS

NUR
SYALIYANA
BINTI ABU
SAMAH

CAUSES

NOR ATHIRAH
BINTI
ZALBADOR

HOW PEOPLE
WITH
DISORDER
METABOLIZE
GLYCOGEN
AEROBICALLY

AINUL IZZATTI

FUNCTION