Page 32 - General Biochemistry

• It is an X-linked recessive hereditary disease characterised by abnormally
low levels of the glucose-6-phosphate dehydrogenase enzyme (abbreviated
G6PD or G6PDH).

• Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose
phosphate pathway, a metabolic pathway that supplies reducing energy to
cells by maintaining the level of the co-enzyme nicotinamide adenine
dinucleotide phosphate (NADPH).

• The NADPH in turn maintains the level of glutathione in these cells that
helps to protect the red blood cells against oxidative damage.

• G6PD converts glucose-6-phosphate into 6-phosphogluconolactone and is
the rate- limiting enzyme of the pentose phosphate pathway.

• Patients with G6PD deficiency are at risk of hemolytic anemia in states of
oxidative stress.

• Individuals with the disease may exhibit non-immune hemolytic anemia in
response to a number of causes.

• This can be due to severe infection, medication and certain foods. Broad
beans contain high levels of vicine, divicine, convicine and isouramil—all
are oxidants. In states of oxidative stress, all remaining glutathione is
consumed.

• Enzymes and other proteins (including hemoglobin) are subsequently
damaged by the oxidants, leading to electrolyte imbalance, membrane cross-
bonding and phagocytosis and splenic sequestration of red blood cells.

• The hemoglobin is metabolized to bilirubin (causing jaundice at high
concentrations) or excreted directly by the kidney (causing acute renal
failure in severe cases).

• Deficiency of G6PD in the alternative pathway causes the build-up of
glucose and thus there is an increase of advanced glycation end products
(AGE).

• The deficiency also causes a reduction of NADPH which is necessary for the
formation of Nitric Oxide (NO).

• The high prevalence of diabetes mellitus type 2 and hypertension in Afro-
Caribbean’s in the West could be directly related to G6PD deficiency.

• Patients are almost exclusively male, due to the X-linked pattern of
inheritance.

• Female carriers can be clinically affected due to lyonization where random
inactivation of an

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