1. The document discusses alanine aminotransferase (ALAT/ALT), an enzyme that plays important roles in amino acid and carbohydrate metabolism.
2. ALT catalyzes the reversible transfer of amino groups between glutamate and pyruvate, and is important for liver gluconeogenesis and the glucose-alanine cycle.
3. Clinically, ALT levels are measured as a biomarker for liver health, with elevated levels indicating potential liver damage from conditions like hepatitis, fatty liver disease, or alcohol use.
2. LEARNING OUTCOMES
1. Describe the structure and function of ALAT.
2. Describe the roles of ALAT in carbohydrate
metabolism.
3. Explain the catalytic action of the ALAT.
4. Explain the clinical significance if ALAT.
5. Correlate knowledge on ALAT with that of Al-
Quran and Sunnah.
4. Structure & Function
Alanine aminotransaminase (ALAT) is
a transaminase enzyme (EC 2.6.1.2).
Also called alanine transferase (ALT)
Formerly called serum glutamate-pyruvate
transaminase (SGPT) or serum glutamic-pyruvic
transaminase (SGPT).
Homodimeric
Cytoplasmic pyridoxal phosphate-dependent
(coenzyme)
Found in plasma and in various body tissues,
greatest abundance in the liver, lesser extent in
kidneys, heart and brain.
5. Structure and Function
Involved in cellular nitrogen metabolism, amino acid
metabolism, and liver gluconeogenesis.
Catalyzes the two parts of the alanine cycle.
Serum ALT level,
Serum AST level,
Their ratio (AST/ALT ratio)
Commonly measured
clinically as
biomarkers for liver
health.
6. Structure & Function
ALT catalyzes the transfer of an amino group
from L-alanine to α-ketoglutarate, the products of
this reversible transamination reaction
being pyruvate and L-glutamate.
L-glutamate + pyruvate ⇌ α-ketoglutarate + L-alanine
8. Roles of ALT in carbohydrate
metabolism.
Liver Gluconeogenesis
In the conversion of alanine
to glucose
9. Glucose- Alanine Cycle
During extended periods of fasting, skeletal
muscle is degraded as an alternative source of
energy.
When muscle (protein) is degraded, alanine is the
major amino acid present.
The glucose-alanine cycle occurs in skeletal
muscle to eliminate nitrogen while replenishing the
energy supply for muscles.
The amino group transported from the muscle to
the liver in the form of alanine, is converted to urea
in the urea cycle and excreted.
12. Catalytication of ALT
ALT catalyzes the reversible transfer of the amino group from
glutamate to pyruvate while
replacing the amino group of glutamate with a carbonyl group
L-glutamate + pyruvate ⇌ α-ketoglutarate + L-alanine
13. • The reaction catalyzed by ALT requires the
cofactor pyridoxal-5’-phosphate (P5P), the
active form of vitamin B6.
• P5P binds covalently but reversibly to an active
site lysine
• This helps catalyze the reaction by accepting
the amino group from the amino acid then
transferring it to carbonyl compound.
Catalytication of ALT
15. ALT as a Measure of Overall Health
and Mortality Risk
ALT activity correlates with the risk of
cardiovascular mortality.
Compared with those with ALT 20 U/L, men
with ALT 100 U/L had nearly 3 times the risk of
death from cardiovascular causes.
The effect of ALT was much larger on liver-
specific mortality.
Compared to those with ALT 20 U/L, men with
ALT 100 U/L had 59 times the risk of death
from liver disease.
16. Uses in liver function test (LFT)
ALT is one of the sensitive markers that is used
as an indicator for Liver disease(along with AST)
When liver cells are damaged or destroyed, the
enzymes in the cells leak out into the blood, in
the blood raising the enzyme levels in the blood,
where they can be measured by blood test, in
which in this case both will be elevated.
In liver disease the amount of ALT ≥ AST.
IN CHRONIC HEPATITIS C : The patients have
already experienced ALT peak before the level
fall over time.
17. Among of the liver diseases :
Non-alcoholic Fatty Liver Disease (NAFLD)
Alcoholic Liver Disease (ALD)
Hepatitis
Drug-Induced Hepatotoxicity
Autoimmune and Cholestatic Liver Diseases
Cirrhosis
Hepatic Ischemia
18. Causes :
a high alcohol intake
a history or known or possible exposure to hep
atitis viruses
obesity or diabetes
a history of consumption of potentially hepatot
oxic drugs
a family history of liver disease.
19. Level of ALT with Cardiac Infarction
Increase of ALT level only can be detected in
minority of the patients since in Cardiac
Infarction, AST is the main indicator.
However, in severe myocardial infarction
damage of the liver due to hypoxia can
increase the ALT level in a few days after
onset.
20. Specific ALT level
Normal range of ALT is between 5 IU/L to 60 IU/L.
Above 60 IU/L but below 300 IU/L, can indicate
any kind of liver disease or just a normal level for
that particular person.
Levels 1,000 IU/L or above, indicate liver damage
from drugs, toxins, viral hepatitis or lack of oxygen
to the liver due to heart attack.
Moderately high ALT levels between 300 IU/L and
1,000 IU/L indicate acute or chronic hepatitis
22. عمران آل سورة(191-190)
190. Indeed, in the creation of the heavens and the earth and the
alternation of the night and the day are signs for those of
understanding.
191. Who remember Allah while standing or sitting or (lying) on their
sides and give thought to the creation of the heavens and the earth,
(saying), "Our Lord, You did not create this aimlessly; exalted are
You (above such a thing); then protect us from the punishment of the
Fire.
23. Hadith 6 Imam Nawawi
ْعنَق ،امُهْنع ُ هاَّلل ي ِضر ٍيرِشب ِْنب ِانمْعُّنال ِ هاَّلل ِدْبع يِبأال:سلم و عليه هللا صلى ِ هاَّلل ولُسر تْعِمس
ُلوُقي" :ُمُأ امُهْنيبو ،ٌنِِّيب امرحْال هنِإو ،ٌنِِّيب لَلحْال هنإِاسهنال ْنِم ٌيرِثك هنُهُملْعي َل ٌاتهِبتْشُم ٌورْنمف ،
ِف عقو ْنمو ،ِه ِض ْرِعو ِهِنيِدِل أْربتْسا دْقف ِتاهُبُّشال ىقهتاي يِعاهالرك ،ِامرحْال يِف عقو ِتاهُبُّشال يْرىع
م ِح ٍكِلم ِِّلُكِل هنِإو َلأ ،ِهيِف عت ْري ْنأ ُكِشوُي ىم ِحْال ل ْوحَلأ ،ُهُم ِارحم ِ هاَّلل ىم ِح هنِإو َلأ ،ىِف هنِإوي
ف ْتدسف اإذو ،ُهُّلُك ُدسجْال حلص ْتحلص اإذ ةْغضُم ِدسجْالُُْلقْال يِِو َلأ ،ُهُّلُك ُدسجْال دس"
I heard the Messenger of Allah ( ﷺ) say, “That which is lawful is clear
and that which is unlawful is clear, and between the two of them are
doubtful matters about which many people do not know. Thus he who
avoids doubtful matters clears himself in regard to his religion and his
honor, but he who falls into doubtful matters [eventually] falls into that
which is unlawful, like the shepherd who pastures around a sanctuary,
all but grazing therein. Truly every king has a sanctuary, and truly
Allah’s sanctuary is His prohibitions. Truly in the body there is a
morsel of flesh, which, if it be whole, all the body is whole, and
which, if it is diseased, all of [the body] is diseased. Truly, it is
the heart”
(Bukhari and Muslim)