Biochemistry Assignment

Submitted to:
Dr. Muhammad Ijaz
Submitted by:
Aneeza Ahmad FA19-PHM-023
Dua ul Aruj FA19-PHM-004

Vitamin B12 (Cobalamin)

Role in Metabolism
Vitamin b12 also known as Cobalamin is a water-soluble
vitamin. It works as a coenzyme, so it is used in enzyme
catalyzed reactions. Following are the three classes of enzymes
that require B12 to function:
• Methyltransferases
• Isomerases
• Dehydrogenases
Vitamin B12 is used by the body in two forms, either as
methylcobalamin or 5-deoxyadenosyl cobalamin. The enzyme
methionine synthase needs methylcobalamin as a cofactor. This
enzyme is normally involved in the conversion of the amino acid
homocysteine into methionine. 5-Deoxyadenosyl cobalamin is a
cofactor needed by the enzyme that converts l-methylmalonyl CoA to
succinyl CoA. This conversion is an important step in the extraction of
energy from proteins and fats. In addition, succinyl CoA is necessary to
produce hemoglobin which is the substance that carries oxygen in red
blood cells.
Methionine Cycle:
Vitamin B12 (cobalamin) plays an important role in the conversion of
homocysteine to methionine in methionine cycle, as it takes the methyl group
from 5-methyl tetrahydrofolate (folic acid) and forms methyl cobalamin which
then releases this methyl group in order to convert homocysteine into
methionine. Moreover, cobalamin is needed in the conversion of the methionine
to homocysteine, where methionine is converted to SAM (S-adenosyl methionine)
product in the presence of ATP by methionine adenosyl transferase. In case of
deficiency of vitamin B12, the body does not have the ability to produce
methionine, which can cause many problems.
Conversion of Methylmalonyl coenzyme A (CoA) to succinyl
CoA:
Two molecules of adenosyl cobalamin are required to convert methylmalonyl CoA
to succinyl CoA, which is a TCA cycle intermediate, through methylmalonyl CoA
mutase enzyme, while propionyl CoA is converted to d-methylmalonyl CoA. In
case of vitamin B12 deficiency, methylmalonyl CoA mutase activity is impaired
and there is accumulation of methylmalonic acid inside the body. These
impairments lead to many problems and issues. The body loses its ability to
produce the TCA cycle intermediate, succinyl CoA, which will lead to an
impairment of TCA cycle as there is reduced conversion of succinate to fumarate,
malate, and to the end product of the cycle, which is responsible for providing
small amount of energy before going to electron transport chain which is
responsible of high energy production. There is also an impairment in
gluconeogenesis, which is the metabolic pathway responsible for generating
glucose from non-carbohydrate substances.