Biochemistry Case study

GUIDE

Sem 1 2015/2016

CASE 1 : Fluoroacetate Toxic

A man was found having nausea, vomiting and abdominal pain,

sweating, confusion and agitation follow. His next of kin told the
triage that he accidentally swallow a rodent poison, which he
thought it is some kind of candy placed on the kitchen table. The
lab results were positive for fluoroacetate toxic.
As a pathology researcher, you have to explain the whole
situation (biochemically) to a bunch of industrial trainees in your
pathology lab.

focus
1. what is the effect of fluoroacetate to the
concentrations of the intermediates in the
citric acid cycle
2. why is it possible.
3. how to overcome the cycle blockage.

1. Acetyl CoA + OAA Citrate

Citrate synthase]
2. Citrate Isocitrate
Aconitase]

[Hydration :

[Dehydration :

1. Fluroacetate + CoASH Fluoroacetyl CoA

2. Fluoroacetyl CoA fluorocitrate [use Citrate
synthase]
3. fluorocitrate Isocitrate
Aconitase]

[inhibit by binding to

What are the impacts?

Treatment?
http://www.inchem.org/documents/pds/pds/pest16_e.htm
treatment for sodium fluoroacetate poisoning is mainly
symptomatic.
If ingested, vomiting should be induced immediately followed by
gastric lavage with two to four litres of tap water and instillation of
15-30 g of saline cathartic.
Monoacetin (glyceryl monoacetate) 0.5 mg/kg should be injected
IM every half hour for 12 hours varying the injection sites.
Artificial respiration with the assistance of oxygen may be
required.
Calcium gluconate, 2-3 g per day in 10% solution may be given
IV.
To control convulsions barbiturates (preferably phenobarbitone or

CASE 2:
Cholesterol

A form 6 student share a news with you.

I am shocked when I look at my blood test result.
My blood total cholesterol is more than 300 mg/dL, the LDL cholesterol is be
more than 220 mg/dL, but my Triglyceride levels tend to be normal, which are
below 150 mg/dL. I am still young!
I have a healthy lifestyle because I do not want to be like my mother who is
having hypercholesterol. Am I having Tangiers disease?.
Explain him the condition and things he can do to help himself. Explain what is
Tangiers disease too.

focus
1. Why blood cholesterol is high in Familial
hypercholesterolemia?
2. What is Tangiers disease?

Refer to Nur Syahira and Team presentation

https://drive.google.com/file/d/0B6z-6U_XfBNmQXhCZW
1TQXdnWU0/view?usp=
sharing

CASE 3: Carnitine
Deficiency

A teenage boy was brought to a hospital as he complaints that he used

to get too tired when asked to participate in the marching team. The
doctor found muscle weakness in the boys arms and legs. From the
muscle biopsy, the lab pathologist found greatly elevated amount of
triglycerides esterified with primary long chain fatty acid. They also fund
significant presence of lipid vacuoles in the muscle biopsy. What causes
these symptoms?

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

Refer to Cek and Team presentation

https://drive.google.com/file/d/0B6z-6U_XfBNmMGFUSzRT
aDY4RFk/view?usp
=sharing

CASE 4: Lactic
acidosis
Lactic acidosis is a physiological condition characterized by low
pH in body tissues and blood (acidosis) accompanied by the
buildup of lactate, especially L-lactate, and is considered a
distinct form of metabolic acidosis. Lactic acidosis is
characterized by lactate levels >5mmol/L and serum pH <7.35.

In a Young Biochemist Association Forum, you are invited to

explain about the condition and how DCA could treat it.

focus
1. why is activity of the pyruvate dehydrogenase complex
can be decreased by low oxygen level?
[ think of the effect of low oxygen level in cells]
2. how the activity of pyruvate dehydrogenase complex is
affected by dichloroacetate?
[understand the DCA actions on PDK]

Cause to PDH kinases to phosphorylate the PDH into inactive

form
Cause to inhibit PDH Kinases, therefore PDH kinases cannot
phosphorylate PDH and PDH becomes active

inactive form

Active form

Lactic acidosis
PDC is regulated in part by reversible
phosphorylation.
A phosphorylated PDH enzyme is in its inactive
state
If PDC kinase catalyses the phosphorylation
(inactivation) of PDC, it will inhibit pyruvate
oxidation
If a persistent glycolysis occur without pyruvate
oxidation, it will lead to accumulation of lactate.
Every molecule of lactate produced is accompanied
by the generation of a hydrogen ion

Examples: How LA may

occur
1. Mutations of subunits of the PDC system that impair the
activity of the enzyme complex are likely to lead to
lactate accumulation.
2. Patients with PDC deficiency do not oxidize carbohydrate
efficiently, and carbohydrate containing meals may lead
to lactic acidosis
3. Patients with defects of the electron transport chain also
develop abnormal lactate accumulation.
1. Impaired electron transfer through the respiratory
chain prevents oxidation of NADH and FADH 2
produced by the PDC reaction and the tricarboxylic
acid cycle, and ATP levels fall.
2. The consequent rise in the intramitochondrial
NADH/NAD ratio inhibits PDC activity, pyruvate
oxidation decreases, and pyruvate is converted to

DCA treatment
The primary mechanism is activation of PDC
( accelerating the oxidation pyruvate to
acetyl CoA.)
DCA is a potent inhibitor of PDH kinases
DCA increases PDC activity by inhibiting the
activity of PDH
Kinase in all tissues

When PDC kinase is inhibited, PDH will be in

its unphosphorylated (active) form.
Active form of PDH will start the oxidation of

REVIEW

Production of Energy from

Glucose

Shuttle
system

Malate-Aspartate shuttle

Glycerol-3-phosphate shuttle

Location

Heart and liver

Skeletal muscle and brain

Pathway

Electrons from cytoplasmic NADH are

carried by malate through the inner
membrane

Electrons from cytoplasmic NADH are

oxidized to form Glycerol-3-phosphate

Malate is oxidized in matrix to form

OAA

Glycerol-3-phosphate is oxidized to form

DHAP

Enzyme used is mitochondrial malate

dehydrogenase
an NAD-linked enzyme

Enzyme used is glycerol-3-phosphate

dehydrogenase
a FAD-linked enzyme

Electrons in NADH enter ETC

Electrons in FADH2 enter ETC

3 ATP are formed

2 ATP are formed

ATP