Megaloblastic Anemia: Folate and Vitamin B12 Metabolism, Causes, diagnosis and therapy

Fig. Megaloblastic anemia showing megaloblastics cells

MACROCYTOSIS

An increased MCV can be due to a number of reasons but careful review of the patient's history and blood smear can narrow the diagnostic possibilities.  The differential can be divided into two broad categories based on RBC morphology.

Round macrocytosis-due to abnormal lipid composition of the eryth­rocyte membrane.  Common etiologies include:

            1. Alcoholism.

            2. Liver Disease.

            3. Renal Disease.

            4. Hypothyroidism ("myxedema of the red cell").

RBC Metabolism Notes (Part 5) : Role of Vitamin B12 and Pernicious anemia

COBALAMIN (Vitamin B₁₂)

• Vitamin B₁₂ is required in humans for two essential enzymatic reactions: the synthesis of methionine and the isomerization of methylmalonyl CoA that arises from the fatty acids with odd numbers of carbon atoms (Fig 28.10).

• When the vitamin is deficient, abnormal fatty acids accumulate and become incorporated into cell membranes, including those of the nervous system. 
  
  

RBC Metabolism Notes (Part 4) : Maturation of RBC and role of Folic acid

MATURATION OF RBC - ROLE OF FOLIC ACID & VITAMIN B12 IN DNA SYNTHESIS

 

FOLIC ACID

• Folic acid (or folate) plays a key role in one-carbon metabolism, and is essential for the biosynthesis of the purines and the pyrimidine, thymine. 
   
• Folic acid deficiency is probably the most common vitamin deficiency in the U.S., particularly among pregnant women and alcoholics.

Structure of Folic Acid

• Folic acid is composed of a pterin ring attached to p-aminobenzoic acid (PABA) and conjugated with one or more glutamic acid residues.

RBC Metabolism Notes (Part 3) : Energy metabolism

ENERGY METABOLISM

• 

  Although the mature red cell contains the enzymes required for glycogen metabolism, the balance between synthesis and utilization is such that no significant amount of glycogen accumulates within the cell under normal circumstances. 
  
  
• Glycogen may accumulate, however, in glycogen storage diseases types III and VI.

RBC Metabolism (Part 2) : Mechanisms of preventing oxidative denaturation of hemoglobin

• 

  Fig. Enzyme that converts MetHb to Hb

  Known mechanisms of preventing or reversing oxidative denaturation of hemoglobin in the erythrocyte include 
• the methemoglobin reductases
• superoxide dismutase
• glutathione peroxidase
• catalase.

(Fig. in left NADH_cytochrome_B5_reductase)

Methemoglobin Reduction

• Most methemoglobin in the erythrocyte is reduced through the action of an enzyme cytochrome b5 methemoglobin reductase, which acts in the presence of two electrons carriers, cytochrome b5, and NADH.

RBC Metabolism Notes (Part 1) : Stages of oxidative denaturation of Hemoglobin

OXIDATIVE DENATURATION OF HEMOGLOBIN: IT’S REVERSIBILITY AND PREVENTION

INTRODUCTION

• Oxyhemoglobin in solution gradually undergoes autoxidation, becoming methemoglobin (HbFe⁺⁺⁺).
• The rate of oxidation is enhanced by conditions such as increased temperature, decreased pH and presence of organic phosphate and of metal ions, and partial oxygenation of hemoglobin. To bind oxygen reversibly, however, the iron in the heme moiety must be maintained in the reduced (ferrous Fe⁺⁺) state, despite exposure to a variety of