Ciclo de Krebs: Reacciones, regulación y papel en enfermedad [COMPLETO]

Ciclo de Krebs y su Importancia Metabólica

Introducción al Ciclo de Krebs

• El video aborda el ciclo de Krebs, sus reacciones bioquímicas, regulación y su relevancia metabólica para la salud humana.

• Se menciona que la glucólisis es la primera ruta para oxidar sustancias orgánicas como la glucosa, siendo el ciclo de Krebs una etapa posterior que completa esta oxidación.

Respiración Celular

• La respiración celular se lleva a cabo en tres etapas:

• Oxidación de moléculas como glucosa y ácidos grasos.

• Entrada del grupo acetil en el ciclo de Krebs.

• Transferencia de electrones a oxígeno en la cadena de transporte.

• En el ciclo de Krebs, los grupos acetil se oxidan a dióxido de carbono, liberando energía almacenada en transportadores reducidos (NADH y FADH2).

Proceso del Ciclo de Krebs

• El ciclo también se conoce como ciclo de los ácidos tricarboxílicos o ácido cítrico; ocurre en la matriz mitocondrial en eucariotas.

• La acetil coenzima A proviene del piruvato generado durante la glucólisis, donde cada piruvato se convierte en un grupo acetilo.

Reacciones Bioquímicas Clave

• La conversión del piruvato a acetil coenzima A es mediada por el complejo piruvato deshidrogenasa, que incluye enzimas derivadas de vitaminas esenciales (tiamina y riboflavina).

• Durante esta reacción se libera CO2; el grupo acetilo resultante tiene dos carbonos.

Primeras Reacciones del Ciclo

• La primera reacción implica la condensación entre acetil coenzima A y oxaloacetato para formar citrato (6 carbonos), catalizada por citrato sintasa.

• En una segunda reacción reversible, el isocitrato se convierte en alfa-cetoglutarato mediante descarboxilación oxidativa con ayuda de iso-citrato deshidrogenasa.

Continuación del Ciclo

• El alfa-cetoglutarato es transformado nuevamente mediante descarboxilación por alfa-cetoglutarato deshidrogenasa; aquí también se produce NADH crucial para ATP posteriormente.

Krebs Cycle: Key Reactions and Metabolic Roles

Enzymatic Reactions in the Krebs Cycle

• The enzyme succinate dehydrogenase, found in eukaryotic organisms, is anchored to the inner mitochondrial membrane. It catalyzes a reversible reaction that produces FADH2, which transports electrons for ATP synthesis during oxidative phosphorylation.

• The conversion of fumarate to malate is facilitated by the enzyme fumarase. In the final step of the Krebs cycle, malate is oxidized to oxaloacetate by malate dehydrogenase, generating a third NADH.

Products and Functions of the Krebs Cycle

• The products of one complete turn of the Krebs cycle include 3 NADH, 1 FADH2, 2 CO2, and 1 GTP (equivalent to ATP). This cycle plays a crucial role in both catabolism and anabolism within eukaryotic cells.

• The Krebs cycle provides metabolites for various metabolic pathways. For instance:

• Citrate contributes to fatty acid and sterol biosynthesis.

• Alpha-ketoglutarate aids in glutamate synthesis and subsequently purines and amino acids like arginine and proline.

Anaplerotic Reactions

• Anaplerotic reactions restore components that exit the Krebs cycle. A significant example occurs in the liver and kidneys where pyruvate carboxylase converts pyruvate into oxaloacetate when there’s a deficiency.

• Other anaplerotic reactions include forming oxaloacetate from phosphoenolpyruvate (PEP) or converting pyruvate into malate via malic enzyme.

Regulation of the Krebs Cycle

• The regulation of the Krebs cycle prevents excessive production or waste of metabolic components. High levels of ATP, NADH, acetyl-CoA, or fatty acids signal sufficient energy availability.

• Conversely, low energy indicators such as unoxidized NAD+ activate certain enzymes to promote continued cycling. For example:

• Pyruvate dehydrogenase can be negatively regulated by ATP but positively activated by ADP.

Implications for Health and Disease

• Disruptions in enzymatic functions within the Krebs cycle can lead to diseases. Genetic mutations affecting these enzymes are rare but can have severe consequences; for instance:

• Mutations in fumarase gene may result in tumors affecting muscle tissue or kidneys.

• Environmental factors also impact this cycle; unhealthy diets can disrupt metabolism leading to health issues. Recent studies highlight its role beyond metabolism—specifically its involvement in immune cell activation.

• Intermediates from the Krebs cycle are implicated in cellular signaling processes essential for immune responses against infections and cancer development.

Disruption in the Krebs Cycle and Its Implications

Impact on Fetal Health

• The fetus exhibits disruptions in certain steps of the Krebs cycle, potentially leading to cardiac issues at birth.

• Alterations in the Krebs cycle result in increased cortisol levels, which may contribute to these health problems.

• The Krebs cycle plays a critical role in energy metabolism, generating key molecules such as GTP, NADH, and FADH2.

Role of the Krebs Cycle

• The Krebs cycle integrates both anabolic and catabolic processes, serving as a central metabolic hub.

• A deeper understanding of this cycle is essential not only for metabolic insights but also for its role in cellular signaling.