BIOSINTESIS DE LIPIDOS (Ácidos grasos, Triacilglicéridos y Colesterol)

Biosynthesis of Lipids Overview

In this presentation, the focus is on the biosynthesis of lipids, specifically the synthesis of fatty acids, triglycerides, and cholesterol. The process involves utilizing excess caloric intake or acetyl-CoA for fatty acid synthesis.

Biosynthesis of Fatty Acids

• Fatty acid synthesis occurs in the cytoplasm through a multi-enzymatic complex that synthesizes neutral lipids like triglycerides stored in adipose tissue.

• Contrary to earlier beliefs about mitochondrial involvement, fatty acid synthesis primarily takes place outside the mitochondria in the cytoplasm.

Citrate Shuttle Mechanism

• To transport citrate from mitochondria to the cytoplasm for fatty acid synthesis, cells use a citrate shuttle mechanism similar to reactions in the Krebs cycle.

• Acetate within mitochondria combines with acetyl-CoA to form citrate before being transported out for further processing.

Fatty Acid Synthesis Pathway

The pathway involves converting citrate back into acetyl-CoA in the cytosol for fatty acid synthesis through various enzymatic reactions.

Conversion Process

• Citrate breaks down into acetyl-CoA and oxaloacetate catalyzed by ATP-dependent enzymes.

• Acetyl-CoA is then converted back into citrate using energy and CoA with an enzyme called citrate lyase before entering fatty acid synthesis.

Malonyl-CoA Formation

Malonyl-CoA formation is crucial for initiating fatty acid synthesis by adding a carboxyl group to acetyl-CoA.

Malonyl-CoA Formation

• Malonyl-CoA is formed by carboxylating acetyl-CoA using biotin-dependent enzyme acetyl-CoA carboxylase (ACC).

• This reaction consumes energy and produces malonyl-CoA essential for subsequent steps in fatty acid biosynthesis.

Fatty Acid Synthase Complex

The fatty acid synthase complex plays a pivotal role in synthesizing palmitic acid (palmitate), a saturated 16-carbon fatty acid.

Fatty Acid Synthase Structure

• The complex consists of two identical subunits with distinct domains responsible for different enzymatic functions.

Contact with Enzymes and Transfer Processes

This section discusses the interaction with enzymes and the transfer processes involved in moving molecules within a biological system.

Contact with Enzyme 2 and Transfer Process

• Contact with enzyme 2 involves zlámal o'neal transferase, transferring malonyl portion to carrier protein.

• The transferase of subunit 2 moves the malonyl group to the carrier protein of subunit 1.

• The malonyl group is then condensed by condensing enzyme of subunit 2.

Condensation Reaction and Enzymatic Processes

This part delves into condensation reactions and enzymatic activities crucial for molecular transformations.

Condensation Reaction Initiation

• Condensation reaction occurs between acetyl-CoA and malonyl attached to carrier proteins.

• Catalyzed by condensing enzyme, resulting in acetoacetyl ACP formation.

Reduction and Dehydration Steps

Focuses on reduction and dehydration steps in the biochemical pathway.

Reduction by Enzyme 4

• Enzyme 4 reduces acetoacetyl ACP to hydroxybutyric acid ACP by adding protons.

• Transformation maintains attachment to carrier protein.

Deshydration Process and Unsaturated Molecule Formation

Explores dehydration process leading to unsaturated molecule formation in the metabolic pathway.

Dehydration by Enzyme 5

• Enzyme 5 dehydrates hydroxybutyric acid ACP, forming an unsaturated molecule through water removal.

• Resulting compound contains a double bond at carbon position due to dehydration process.

Unsaturation Process via Enoyl Reductase

Discusses unsaturation process facilitated by enoyl reductase enzyme in metabolic reactions.

Unsaturation Transformation

• Enoyl reductase (enzyme 6) reduces unsaturated molecule, adding protons for saturation.

• Carbon position changes from double bond to single bond through reduction process.

Palmitate Synthesis Pathway Completion

Details completion of palmitate synthesis pathway involving multiple enzymatic steps.

Palmitate Formation

• Final enzymatic step involves cleavage of four-carbon unit from ACP chain by enzyme 7.

• Repeated cycles lead to palmitate synthesis comprising sixteen carbon atoms.

Fatty Acid Elongation Mechanism

Explores fatty acid elongation mechanism essential for synthesizing longer-chain fatty acids beyond palmitate.

Fatty Acid Elongation Process

• Cells elongate fatty acids using malonyl-CoA as carbon source for extending chain length.

Lipid Biosynthesis Pathways

This section delves into the intricate processes involved in lipid biosynthesis, focusing on the conversion of fatty acids and the synthesis of triglycerides and cholesterol.

Activation of Fatty Acids

• Aire introduces a double bond to palmitic acid, converting it to palmitoleic acid by activating fatty acids and adding a double bond between carbon 9 and carbon 10.

• Enzymes like delta 9 desaturase play a crucial role in placing the double bond at carbon 9.

Triglyceride Synthesis

• During polyunsaturated fatty acid synthesis, two water molecules are released as hydrogen atoms from previous reactions contribute to forming new double bonds.

• Cells utilize monounsaturated fatty acids as substrates for synthesizing polyunsaturated fatty acids through enzyme-catalyzed addition of new double bonds separated by two carbon atoms.

Triglyceride Formation

• Triglyceride synthesis requires glycerol activation catalyzed by kinases and activation of fatty acids facilitated by thio kinases.

• Enzymes involved in triglyceride biosynthesis are located in the smooth endoplasmic reticulum.

Cholesterol Biosynthesis

• Cholesterol biosynthesis is complex, involving 33 phases divided into three major stages: condensation, reduction, and transformation into cholesterol.

• Acetate molecules are converted to mevalonate through a series of enzymatic reactions in the smooth endoplasmic reticulum.

Mevalonate Transformation

• Acetyl-CoA combines with another acetyl-CoA molecule to form hydroxymethylglutaryl-CoA (HMG-CoA), which undergoes further transformations catalyzed by enzymes like hydroxymethylglutaryl-CoA synthase.

Synthesis of Fatty Acids and Cholesterol

The transcript discusses the synthesis of fatty acids and cholesterol, detailing the molecular processes involved in these metabolic pathways.

Pirofosfato Molecule Formation

• Pirofosfato molecule consists of 10 carbon atoms, each with 5 carbon atoms.

• Isopentenyl pyrophosphate combines with pirofosfato to form a 15-carbon pirofosfato product called squalene.

Squalene Formation and Transformation

• Two molecules of 15-carbon atoms combine to form squalene.

• Squalene transforms into a 30-carbon atom molecule known as escualeno, which further converts into cholesterol through complex reactions.

Regulation of Metabolic Pathways

This section delves into the regulation of metabolic pathways involved in fatty acid and cholesterol biosynthesis.

Regulation Mechanisms

• In fatty acid biosynthesis, acetyl-CoA carboxylase is the key regulatory enzyme.

• Insulin activates acetyl-CoA carboxylase by dephosphorylation, promoting fatty acid synthesis.

Citrate and Palmitoyl-CoA Regulation

• Citrate activates acetyl-CoA carboxylase while palmitoyl-CoA inhibits it upon excessive fatty acid synthesis.

Cholesterol Synthesis Pathway

Focuses on the primary enzyme regulating cholesterol synthesis pathway and its modulation.

Key Enzyme Function

• HMG-CoA reductase is crucial in converting mevalonate to cholesterol precursor molecules.

• Glucagon stimulates HMG-CoA reductase inhibition, while insulin activates it, affecting cellular cholesterol levels.

Conclusion on Lipid Synthesis

Concluding remarks on lipid synthesis emphasizing key points discussed throughout the transcript.

Final Insights

• Triglyceride synthesis requires glycerol activation alongside fatty acids for phosphatidic acid formation leading to triglycerides.