Cholesterol Biosynthesis Pathway - Biochemistry
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Cholesterol Biosynthesis Pathway: Biochemistry
Cholesterol biosynthesis occurs mainly in the liver, but also in other tissues, through a series of intricate enzymatic reactions. The pathway is often referred to as the mevalonate pathway. Here are the key steps:
1. Acetyl-CoA Formation
Acetyl-CoA serves as the primary substrate for cholesterol biosynthesis.
Acetyl-CoA is generated from glucose metabolism via glycolysis and the pyruvate dehydrogenase complex.
2. Formation of 3-Hydroxy-3-Methylglutaryl-CoA (HMG-CoA)
Enzyme involved: HMG-CoA Synthase.
Acetyl-CoA is converted into HMG-CoA.
This step is the rate-limiting and highly regulated step in cholesterol biosynthesis.
3. Conversion of HMG-CoA to Mevalonate
Enzyme involved: HMG-CoA Reductase.
HMG-CoA is reduced to form mevalonate.
HMG-CoA Reductase is a key regulatory enzyme and the target of cholesterol-lowering drugs (statins).
4. Mevalonate to Isopentenyl Pyrophosphate (IPP)
Mevalonate is phosphorylated and decarboxylated to yield isopentenyl pyrophosphate (IPP).
IPP is an important precursor for cholesterol synthesis.
5. Formation of Squalene
Enzyme involved: Squalene Synthase.
IPP molecules are condensed to form squalene.
This step commits the pathway to cholesterol biosynthesis.
6. Squalene to Lanosterol
Squalene undergoes a series of reactions, including cyclization, to form lanosterol.
7. Lanosterol to Cholesterol
A series of enzymatic reactions convert lanosterol into cholesterol.
These reactions include demethylation, isomerization, and reduction steps.
Regulation of Cholesterol Biosynthesis
______________________________________
Cholesterol biosynthesis is tightly regulated to maintain cellular cholesterol homeostasis.
Key regulatory mechanisms include:
Feedback Inhibition: Elevated cellular cholesterol levels inhibit HMG-CoA Reductase, reducing cholesterol synthesis.
Sterol Regulatory Element-Binding Proteins (SREBPs): These transcription factors activate genes involved in cholesterol synthesis when cholesterol levels are low.
Clinical Significance
____________________
Dysregulation of cholesterol biosynthesis can lead to various medical conditions, including hypercholesterolemia and atherosclerosis.
Statins, drugs that inhibit HMG-CoA Reductase, are commonly used to lower cholesterol levels and reduce the risk of cardiovascular diseases.
#CholesterolBiosynthesis #Biochemistry #MevalonatePathway #HMGCoAReductase #CholesterolMetabolism #MedicalBiochemistry #MBBSStudies #Statins #CellularCholesterol #ClinicalBiochemistry
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Cholesterol Biosynthesis Pathway: Biochemistry
Cholesterol biosynthesis occurs mainly in the liver, but also in other tissues, through a series of intricate enzymatic reactions. The pathway is often referred to as the mevalonate pathway. Here are the key steps:
1. Acetyl-CoA Formation
Acetyl-CoA serves as the primary substrate for cholesterol biosynthesis.
Acetyl-CoA is generated from glucose metabolism via glycolysis and the pyruvate dehydrogenase complex.
2. Formation of 3-Hydroxy-3-Methylglutaryl-CoA (HMG-CoA)
Enzyme involved: HMG-CoA Synthase.
Acetyl-CoA is converted into HMG-CoA.
This step is the rate-limiting and highly regulated step in cholesterol biosynthesis.
3. Conversion of HMG-CoA to Mevalonate
Enzyme involved: HMG-CoA Reductase.
HMG-CoA is reduced to form mevalonate.
HMG-CoA Reductase is a key regulatory enzyme and the target of cholesterol-lowering drugs (statins).
4. Mevalonate to Isopentenyl Pyrophosphate (IPP)
Mevalonate is phosphorylated and decarboxylated to yield isopentenyl pyrophosphate (IPP).
IPP is an important precursor for cholesterol synthesis.
5. Formation of Squalene
Enzyme involved: Squalene Synthase.
IPP molecules are condensed to form squalene.
This step commits the pathway to cholesterol biosynthesis.
6. Squalene to Lanosterol
Squalene undergoes a series of reactions, including cyclization, to form lanosterol.
7. Lanosterol to Cholesterol
A series of enzymatic reactions convert lanosterol into cholesterol.
These reactions include demethylation, isomerization, and reduction steps.
Regulation of Cholesterol Biosynthesis
______________________________________
Cholesterol biosynthesis is tightly regulated to maintain cellular cholesterol homeostasis.
Key regulatory mechanisms include:
Feedback Inhibition: Elevated cellular cholesterol levels inhibit HMG-CoA Reductase, reducing cholesterol synthesis.
Sterol Regulatory Element-Binding Proteins (SREBPs): These transcription factors activate genes involved in cholesterol synthesis when cholesterol levels are low.
Clinical Significance
____________________
Dysregulation of cholesterol biosynthesis can lead to various medical conditions, including hypercholesterolemia and atherosclerosis.
Statins, drugs that inhibit HMG-CoA Reductase, are commonly used to lower cholesterol levels and reduce the risk of cardiovascular diseases.
#CholesterolBiosynthesis #Biochemistry #MevalonatePathway #HMGCoAReductase #CholesterolMetabolism #MedicalBiochemistry #MBBSStudies #Statins #CellularCholesterol #ClinicalBiochemistry
#fmge #fmgevideos #rapidrevisionfmge #fmgejan2023 #mbbslectures #nationalexitexam #nationalexittest #neetpg #usmlepreparation #usmlestep1 #fmge #usmle #drgbhanuprakash #medicalstudents #medicalstudent #medicalcollege #neetpg2023 #usmleprep #usmlevideos #usmlestep1videos #medicalstudents #neetpgvideos #cholesterol #biochemistry #biochemistryvideos #biochemistryusmle
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