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L-Lactate Dehydrogenase A Chain (LDHA): A Crucial Enzyme in Metabolism

Endocrinology Diagnostics

Introduction

  • Full name: Lactate dehydrogenase A chain
  • Primary functions:
    • Converts pyruvate to lactate
    • Converts NADH to NAD⁺
  • Important for:
    • Metabolism
    • Quick ATP production
    • Muscle function during exercise

Structure and Function Physical Structure:

  • Contains four subunits
  • Has NAD⁺ binding site
  • Active region for substrate interaction
  • Forms enzyme complex

Key Functions:

  • Supports glycolysis in low oxygen
  • Enables rapid ATP production
  • Converts pyruvate to lactate
  • Replenishes NAD⁺
  • Produces lactate as:
    • Previously thought waste product
    • Now recognized energy source
    • Potential signalling molecule

Health and Disease Metabolic Disorders:

  • Associated with:
    • Acidosis
    • Mitochondrial diseases
    • High blood lactate levels
  • Risk factors:
    • Sepsis
    • Intense physical activity
    • Genetic conditions
  • Connection to diabetes:
    • Affects glucose balance
    • Influences metabolic health

Cancer Metabolism:

  • Involved in Warburg effect
  • Cancer cells prefer glycolysis
  • Elevated LDHA levels lead to:
    • Increased lactate production
    • Acidic tumor environment
    • Enhanced tumor growth
    • Cancer spread
  • Potential therapeutic target

Regulation of Activity Control Factors:

  • Substrate availability
  • pH levels
  • NADH levels
  • Translational changes

Post-translational Modifications:

  • Phosphorylation
  • Acetylation
  • Affected by:
    • Growth factors
    • Stress factors
  • Enables cellular adaptation

Future Perspectives and Research Directions

  • Development of LDHA inhibitors
  • Treatment potential for:
    • Cancer
    • Metabolic disorders
  • Use as disease progression marker
  • Focus on:
    • Understanding balance in health/disease
    • Developing control strategies
    • Innovative treatment approaches
    • Expanding metabolic research
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