ALANINE TRANSAMINASE (ALT)

Everythign you need to know about the enzyme Alanine Transaminase (ALT) aka Alanine Aminotransferase (ALAT). Enjoyyyy!!

1. ALANINE AMINOTRANSFERASE (ALAT) GROUP 6 1141988 MUHAMMAD AZFAR BIN ZAMAURI 1141989 NURUL NASUHA BINTI GHAZALI 1141990 NUR SYAHIRAH SHAHUL HAMEED 1141991 SYAHIRAH BINTI RIZALAFANDI 1141992 NUR MUNIRAH BINTI MOHD AMIN

2. LEARNING OUTCOMES Describe the structure and function of ALAT. Describe the roles of ALAT in carbohydrate metabolism. Explain the catalytic action of the ALAT. Explain the clinical significance if ALAT. Correlate knowledge on ALAT with that of Al-Quran and Sunnah.

3. STRUCTURE AND FUNCTION

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) F ound in  plasma  and in various body tissues, greatest abundance in the  liver, lesser extent in kidneys, heart and brain.

5. Structure and Function I nvolved 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

7. ROLES OF ALT IN CARBOHYDRATE METABOLISM

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. W hen 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.

10. CATALYTIC ACTION OF THE ALT

11. Catalytication of ALT ALT catalyzes the reversible transfer of the amino group from glutamate to pyruvate while r eplacing the amino group of glutamate with a carbonyl group L-glutamate + pyruvate ⇌  α- ketoglutarate  + L-alanine

12. 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

13. CLINICAL SIGNIFICANCE OF ALT

14. 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.

15. 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 .

16. 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

17. Causes : a  high alcohol intake  a  history or known or possible exposure to hepatitis viruses  obesity  or diabetes  a  history of consumption of potentially hepatotoxic drugs  a  family history of liver disease. 

18. 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.

19. 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

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

21. سورة آل عمران (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.

22. Hadith 6 Imam Nawawi َعنْ أَبِي عَبْدِ اللَّهِ النُّعْمَانِ بْنِ بَشِيرٍ رَضِيَ اللَّهُ عَنْهُمَا، قَالَ: سَمِعْت رَسُولَ اللَّهِ صلى الله عليه و سلم يَقُولُ: "إنَّ الْحَلَالَ بَيِّنٌ، وَإِنَّ الْحَرَامَ بَيِّنٌ، وَبَيْنَهُمَا أُمُورٌ مُشْتَبِهَاتٌ لَا يَعْلَمُهُنَّ كَثِيرٌ مِنْ النَّاسِ، فَمَنْ اتَّقَى الشُّبُهَاتِ فَقْد اسْتَبْرَأَ لِدِينِهِ وَعِرْضِهِ، وَمَنْ وَقَعَ فِي الشُّبُهَاتِ وَقَعَ فِي الْحَرَامِ، كَالرَّاعِي يَرْعَى حَوْلَ الْحِمَى يُوشِكُ أَنْ يَرْتَعَ فِيهِ، أَلَا وَإِنَّ لِكُلِّ مَلِكٍ حِمًى، أَلَا وَإِنَّ حِمَى اللَّهِ مَحَارِمُهُ، أَلَا وَإِنَّ فِي الْجَسَدِ مُضْغَةً إذَا صَلَحَتْ صَلَحَ الْجَسَدُ كُلُّهُ، وَإذَا فَسَدَتْ فَسَدَ الْجَسَدُ كُلُّهُ، أَلَا وَهِيَ الْقَلْبُ"  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)

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