CHAPTER 43: COBALAMIN (B12)

OBJECTIVES

  1. Explain why either folic acid or vitamin B12 deficiency could lead to megaloblastic anemia (MA; see Chapter 16).

Megaloblastic anemia is a condition where red blood cells are larger than normal and there are fewer of them. The two most common causes of megaloblastic anemia are deficiencies of vitamin B12 and folate. Folate deficiency can be caused by dietary deficiency, alcoholism, or malabsorption syndromes. Vitamin B12 deficiency can be caused by pernicious anemia or malabsorption syndromes. Copper deficiency, adverse drug reactions, and thiamine-responsive megaloblastic anemia syndrome are other causes of megaloblastic anemia.

Both folic acid and vitamin B12 are essential for the production of red blood cells. A deficiency in either one can lead to megaloblastic anemia. Folic acid is necessary for the synthesis of DNA and RNA. Vitamin B12 is also necessary for DNA synthesis and is involved in the metabolism of folic acid. Without these vitamins, red blood cells cannot divide properly and become larger than normal.

  1. Recognize why folic acid supplementation can partially offset the MA caused by vitamin B12 deficiency, yet have no effect on the homocystinuria.

Folic acid supplementation can partially offset the megaloblastic anemia caused by vitamin B12 deficiency because folic acid can help regenerate red blood cells. However, folic acid supplementation has no effect on homocystinuria because it does not address the underlying metabolic defect.

Homocystinuria is a condition that is associated with significantly increased levels of homocysteine as well as reduced levels of folic acid and vitamin B-12. Patients with homocystinuria most likely need higher doses of folic acid and vitamin B-12. Increasing folic acid dose made a statistically significant but clinically trivial decrease in homocysteine levels, and could not normalize homocysteine level in most patients

  1. Identify the essential trace element required by microbes in the biosynthesis of hydroxocobalamin, and know why liver is a good dietary source of cobalamin.

The essential trace element required by microbes in the biosynthesis of hydroxocobalamin is cobalt. Cobalamin is another name for vitamin B122. Liver is a good dietary source of cobalamin because it is rich in vitamin B12

  1. Name the commercial, mitochondrial and cytoplasmic forms of cobalamin.

The commercial form of cobalamin is cyanocobalamin. The mitochondrial form of cobalamin is adenosylcobalamin. The cytoplasmic form of cobalamin is methylcobalamin.

  1. Identify and discuss the importance of two important enzymatic reactions in animals requiring vitamin B12.

Vitamin B12 is an essential vitamin that plays a crucial role in the metabolism of mammals. It is an essential part of two enzymatic systems involved in multiple metabolic reactions, such as in the metabolism of carbohydrates, lipids, some amino acids and DNA. The two important enzymatic reactions in animals requiring vitamin B12 are:

The remethylation of homocysteine (Hcy) to methionine.

The isomerization of methylmalonyl coenzyme A (CoA), which is produced during the degradation of some amino acids (isoleucine, valine, threonine, and methionine) and fatty acids (FAs) with odd numbers of carbon atoms

  1. Explain why neuronal demyelination is sometimes seen in B12 deficiency (see Chapters 57 & 59).

Vitamin B12 plays a significant role in the synthesis and maintenance of myelin. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Neurological problems occur in most people who are deficient in vitamin B-12

  1. Understand the relationship between gastric (and abomasal) HCl secretion, and pancreatic/biliary HCO3 – secretion to vitamin B12 absorption.

Gastric acid facilitates the absorption of vitamin B12. The acid denatures dietary proteins and releases vitamin B12 from food. The vitamin B12 then binds to R-protein (also called haptocorrin) secreted by salivary glands and stomach mucosa. In the duodenum, pancreatic proteases cleave R-protein from vitamin B12, which then binds to intrinsic factor (IF) secreted by gastric parietal cells. The IF-B12 complex is absorbed in the ileum.

  1. Explain the interactions between dietary protein, R-proteins, gastric and pancreatic proteases and intrinsic factor (IF) in B12 gastrointestinal transport.

Dietary protein is denatured by gastric acid and pepsin in the stomach. This releases vitamin B12 from food. The vitamin B12 then binds to R-protein (also called haptocorrin) secreted by salivary glands and stomach mucosa. In the duodenum, pancreatic proteases cleave R-protein from vitamin B12, which then binds to intrinsic factor (IF) secreted by gastric parietal cells. The IF-B12 complex is absorbed in the ileum.

  1. Indicate why the rate of gastric IF secretion usually parallels the rate of gastric HCl secretion.

The rate of gastric intrinsic factor (IF) secretion usually parallels the rate of gastric hydrochloric acid (HCl) secretion because the same cells that secrete HCl also secrete IF.

  1. Recognize the anatomic relationship between intestinal bile acid and intestinal B12 absorption (see Chapter 62).

Bile acids are required for the absorption of vitamin B12. They are secreted into the duodenum and form micelles with dietary lipids. The micelles facilitate the absorption of vitamin B12 by bringing it into close proximity with the ileal mucosa.

  1. Explain the process of intestinal B12 absorption, transport in blood and storage in the liver.

Vitamin B12 is transported in the blood bound to transcobalamin II (TCII). The liver stores vitamin B12 and releases it into the blood as needed. The liver also synthesizes and secretes haptocorrin (R-protein), which binds to vitamin B12 in the blood. Vitamin B12 bound to haptocorrin is taken up by cells in the bone marrow and other tissues.

  1. Identify various causes of vitamin B12 deficiency, and explain why homocystinuria, methylmalonuria and intestinal dysfunction may become pathophysiologic signs.

Various causes of vitamin B12 deficiency include inadequate dietary intake, malabsorption syndromes, pancreatic insufficiency, and pernicious anemia. Homocystinuria and methylmalonuria may become pathophysiologic signs because they are associated with vitamin B12 deficiency. Intestinal dysfunction may become a pathophysiologic sign because it can lead to malabsorption of vitamin B12.