ALANINE AMINOTRANSFERASE(ALAT)GROUP 6

1141988 MUHAMMAD AZFAR BIN ZAMAURI1141989 NURUL NASUHA BINTI GHAZALI1141990 NUR SYAHIRAH SHAHUL HAMEED1141991 SYAHIRAH BINTI RIZALAFANDI1141992 NUR MUNIRAH BINTI MOHD AMIN

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.

STRUCTURE AND FUNCTION

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.

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.

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

ROLES OF ALT IN CARBOHYDRATE METABOLISM

Roles of ALT in carbohydrate metabolism.

Liver Gluconeogenesis

In the conversion of alanine to glucose

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.

CATALYTIC ACTION OF THE ALT

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

• 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

CLINICAL SIGNIFICANCE OF ALT

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.

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.

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

Causes : a high alcohol intake  a history or known or possible exposure t

o hepatitis viruses  obesity or diabetes  a history of consumption of potentially h

epatotoxic drugs  a family history of liver disease. 

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.

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

CORRELATION OF KNOWLEDGE ON ENZYME WITH THAT OF AL-QURAN AND SUNNAH

عمران آل (190-191 )سورة

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.

Hadith 6 Imam NawawiM : الله صلى ه الل رسول سمعت قال عنهما، ه الل رضي بشير بن عمان الن ه الل عبد أبي عن " : يعلمهrن ال مشتبهات أمور وبينهrما ن، بي الحرام وإن ن، بي الحالل إن يقول سلم و عليهبهات الش في وقع ومن وعرضه، لدينه استبرأ فقد بهات الش قى ات فمن اس، الن من كثير

حمى، ملك لكل وإن أال فيه، يرتع أن rيوشك الحمى حول يرعى اعي كالر الحرام، في وقعوإذا ه، كل الجسد صلح صلحت إذا مضغة الجسد في وإن أال محارمه، ه الل حمى وإن أال

القلب وهي أال ه، كل الجسد فسد  "فسدتI heard the Messenger of Allah (ملسو هيلع هللا ىلص) 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)

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