Diploma in Pharmacy 2nd Year: Biochemistry & Clinical Pathology

Krebs Cycle

• Also known as Citric Acid Cycle or Krebs-Henseleit cycle
• Common metabolic pathway for carbohydrates, fats, and proteins
• First described by Hans Krebs
• Occurs in the matrix of mitochondria
• End product of glycolysis, Pyruvate, enters into mitochondria by active transport and is converted into Acetyl Co-A
• One Krebs cycle completes in the presence of optimal oxygen, generating 12 ATPs
• Catabolism of one glucose in aerobic conditions generates 38 ATPs, including 8 ATPs in glycolysis, 6 ATPs in conversion of Pyruvate to Acetyl-CoA, and 24 ATPs in Krebs cycle

Diseases related to Abnormal Metabolism of Carbohydrates

• Diabetes Mellitus
  • Inherited or acquired disease due to defect in insulin secretion or insulin action, or both
  • Characterized by high blood sugar levels for a long time
  • Symptoms: presence of sugar in urine, increased thirst, increased frequency of urination, extreme hunger, fatigue, blurred vision, headache, frequent infections, delayed healing of cuts and wounds, and itchy skin
• Galactosaemia
  • Genetic disorder in which the body is unable to metabolize galactose sugar, leading to increased blood galactose levels
  • Symptoms: appetite loss, jaundice, liver enlargement, liver damage, and abdominal swelling due to fluid accumulation
• Glycogen Storage Disease (GSD)
  • Breakdown of glycogen to glucose is facilitated by enzymes, but if they are blocked, glycogen accumulates in the liver and muscles, leading to GSD
• Glucose-6-Phosphate Dehydrogenase Deficiency Disease
  • Genetic disorder in which the quantity of Glucose-6-Phosphate Dehydrogenase decreases, causing breakdown of premature RBCs, leading to haemolytic anaemia

Urea Cycle

• Also known as Krebs-Henseleit cycle
• First metabolic cycle to be elucidated by Hans Krebs and Kurt Henseleit (1932)
• Occurs in the liver and is transported to the kidneys for excretion in urine
• Urea is the end product of protein metabolism (amino acid metabolism)
• Nitrogen of amino acids is converted to ammonia, which is toxic to the body, and is then detoxified and converted to urea
• Urea synthesis is a five-step cyclic process involving five distinct enzymes

Diseases related to Abnormal Metabolism of Amino Acids

• Albinism
  • Group of inherited disorders in which tyrosine metabolism does not occur properly, leading to low or no melanin production
  • Symptoms: increased risk of skin cancer, little or no color in hair and skin
• Tyrosinemia
  • Inherited disorder in which metabolism of tyrosine is badly affected, leading to accumulation of tyrosine in body tissues
  • Symptoms: bloody stool, diarrhea, fatigue, vomiting, painful wounds on skin, red eyes, convulsion, and intellectual disability

Biological Oxidation

• Oxidation is a reaction with oxygen directly or indirectly, or the removal of hydrogen or electrons
• Carried out by enzymes
• Electron released by this reaction is accepted by electron acceptors (NAD, FAD), and then ATP formation occurs
• This process takes place in living tissues and is necessary for survival, hence it is called biological oxidation

Electron Transport Chain and Oxidative Phosphorylation

• Electron transport chain is a series of protein complexes and other molecules that accept and transfer electrons from NADH and FADH2 to oxygen, resulting in the synthesis of ATP
• In the formation of ATP, phosphorus is used, and oxidation-reduction reaction is involved, hence it is called oxidative phosphorylation

Ketogenesis

• The synthesis of ketone bodies occurs in the liver
• Ketone bodies are water-soluble and energy-yielding
• Acetyl CoA, formed by oxidation of fatty acids, pyruvate, or some amino acids, is the precursor for ketone bodies
• The three main types of ketone bodies produced are acetone, acetoacetate, and beta-hydroxybutyrate
• Ketone bodies can be used by the brain and other tissues as an alternative energy source when glucose is scarce, and they are also involved in regulating blood glucose levels and reducing inflammation