Formation Of DTTP Required For DNA Synthesis Biology Essay

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THF is then converted to THF polyglutamates, and in a series of reactions, leads to formation of dTTP that is required for DNA synthesis.

Therefore, from what has been said, it is clear that both B12 and folic acid are required for erythropoiesis.

Patient's red blood cell count was very low and so therefore confirms the diagnosis.

B12 and methyl THF are also required for the production of methionine that is converted to S-adenosyl methionine. This substance is important for the methylation of myelin without which peripheral neuropathy results, as is observed in the patient.

B12 is also needed for the isomerisation of methymalonyl CoA to succinyl CoA, a reaction which leads to synthesis of haem. B12 deficiency therefore leads to anaemia and correlates with the low haemoglobin concentration levels of the patient's blood. Also bilirubin is one of the products of haemoglobin catabolism that occurs, which lead to jaundice that is also observed in the patient.

RBCs become megaloblastic as defects in DNA synthesis result in fewer rounds of mitosis. This leads to RBCs being larger than normal. Once again, this correlates with the fact that the patient's mean cell volume of RBCs is higher than the normal range.

Treatment

B12 deficiency can be treated with a course of vitamin injections. Hydroxocobalamin is injected into a muscle once every two to four days, and around six injections are given, which is enough to build up a store of B12 in the body.

The symptoms of anaemia usually improve quickly once treatment has begun. The patient may be advised to have a blood test every year or so to check that the anaemia is being treated successfully.

Maintenance injections of B12 may be required every three months for life to stop the deficiency from coming back.4

Breakfast cereals fortified with B12 and mineral supplements can help to prevent B12 deficiency in strict vegetarians (who do not eat eggs) and vegans. Eating a balanced diet containing meat, fish and dairy foods will also allow patients to get all the B12 they need.

Red blood cell count (RBC)

The red blood cell count is the average number of RBCs per litre of blood.

A low number of RBCs may indicate anaemia and could be the result of blood loss, under-production of red blood cells in the bone marrow, malnutrition (such as iron deficiency), over-hydration, inadequate folate or vitamin B12 intake, or even mechanical damage to red blood cells.2

Haemoglobin (HGB)

HGB is the iron-containing compound found in RBCs. Calculating the concentration of HGB in the blood can help diagnose anaemia.

Hematocrit (HCT)

Hematocrit is a measure of the percentage of red blood cells to the total blood volume.2

A low hematocrit is common in patients suffering from anaemia, blood loss, nutritional deficiencies, or bone marrow failure.

Mean cell volume (MCV)

MCV is the average volume of red blood cells, which can help determine whether or not someone has anaemia.2

Mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC)

The MCH is the average haemoglobin content and the MCHC is the average haemoglobin concentration in a specific volume of RBCs2

The MCH may be high in other types of anaemia where the red blood cells are enlarged (for example, as a result of).

Folic acid or vitamin B12 deficiency may result in a high MCH in certain types of anaemia due to enlarged RBCs.

Red blood cell distribution width (RDW)

RDW is a measure of the variation of red blood cell width. In the case of a mixed iron and vitamin B12 deficiency a mix of both large and small cells will be seen, hence an elevated RDW.

Folate

The concentrations of folate in the serum or plasma reflect the folate intake and stores. Both are low in the patient. In addition, the very low serum value represents a long-term abnormality or prolonged low intake.

Serum lactate dehydrogenase (LDH)

Serum LDH is often used as a marker of tissue breakdown as it is abundant in RBCs and can function as a marker for haemolysis.

Diagnosis: B12/folate deficiency

Macrocytic megaloblastic anaemia is caused by a deficiency of vitamin B12 or folic acid.

Vitamin B12 (B12) is required for the production of RBCs and to keep the nervous system functioning efficiently. It is also required for the absorption of folic acid.

B12 deficiency can arise due to:

Decreased production of intrinsic factor (IF) by the stomach

Decreased intestinal absorption of B12

Inadequate dietary intake of meat, fish and dairy products that are rich in B12

B12 is synthesised by gastric parietal cells and then combines with IF that is produced by the stomach lining. Absorption of B12 occurs via IF receptor (cubilin) binding at the distal ileum.

Symptoms

Symptoms of B12 deficiency include angular glossitis, a rapid/weak pulse, pale/jaundiced skin, breathlessness, dizziness and headaches. If the deficiency goes on for long periods of time then this results in the nervous system being affected as well. In the patient, mild peripheral neuropathy was observed, confirming long-term B12 deficiency.

Symptoms occur due to B12 deficiency caused by a lack of IF. This is termed pernicious anaemia and is an autoimmune disease, whereby the immune system produces auto-antibodies that attack the stomach lining. This results in damage to cells that produce IF and consequently B12 binding cannot occur, resulting in none being absorbed into the body.

As the body cannot synthesise folate, dietary folates are required that are converted to methyl tetrahydrofolate (methyl THF) during absorption through primarily the jejunum.

B12 is the cofactor of the methionine synthase reaction that leads to conversion of homocysteine to methionine. This process also leads to conversion of methyl THF to THF at the same time.

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