the metabolic pathways in living
organisms has been a
prerequisite to understanding the
nature of many diseases
1908 Archibald Garrod appreciated that diseases can be caused by the
genetically determined absence or modification of specific enzymes
Garrod reported only four cases
These hereditary defects of metabolism are rare, can have
disastrous consequences for the young children who are affected,
fibrosis and galactosaemia.
Metabolic fuels derived of
Carbohydrates, fats and proteins
Diagnosis of an inherited metabolic disorder can involve measuring
the activity of a given enzyme in a sample taken from an accessible
tissue, such as blood cells.
If a patient lacks enzyme consequences may be observed.d, the following
Reduced formation of E and X. If either o condition may result r both are
essential cell products, with no alternative route for their synthesis, a
deficiency ccumulation of C and possibly A. If these substances are toxic,
cell damage mayresult Increased levels of Z.
The production of this molecule is now enhanced
and it may be toxic.The increased amounts of C
and Z may accumulate in the blood and,
subsequently, can be excreted in the urine.
example of a metabolic disorder
phenylketonuria, which results from the inability to convert the amino acid
phenylalanine (C) into tyrosine (E).This is due to the lack of phenylalanine
hydroxylase (enzyme d) activity, which is normally present in the liver.
he defective gene is associated with a chloride ion channel in epithelial cells, which
results in abnormal elec- trolyte reabsorption
Cholera a usurper of
is an infectious disease, contracted by drinking water
containing the bacterium Vibrio cholerae.
The vibrios colonize and adhere to the sma secrete a
protein exotoxin called choleragen
The toxine molecule is made in two parts, knows as subunits A and B. Subunit B Binds strongly to a
specific, complex lipid repector in the cell membrane. Subunit A,wich is responsible for cell toxicity, then
gains entry to the cell.
Diabetes mellitus: catabolic disease
In the kidneys, filtered glucose isas exceeded reabsorbed, but when blood glucose levels of 10 mM a gh
blood glucose concentrations (hyper- rom an increased ke by muscle and reab- normally mpl sorption
becomes saturated and glucose appear osmotically enhances water excretion and stimulae
classical symptoms of the diseases in the urine
In non-diabetics, the blood glucose will
havereturned normal levels, whereas in the
diabetic it will remain high above 11 mM.
be an anabolic hormone that functions to
coordinate the metabo processes in a
number of body tissues. A lack of insulin
will, therefore lead to enhanced catabolism
Alcoholic liver disease: damage by metabolism
increased formation of fibrous tissue destroys the normal
liver lobule structure and seriously disturbs hepatic functions
alcohol abuse aver a period of 10-20 years can result in cirrhosts
The principal enzymes involved are alcohol dehydrogenase (ADH),
located in the cytoplasm and aldehyde dehydrogenase (ALDH),
predominantly associated with mitochondria
Alcohol metabolism inhibit liver gluconeogenesis
from lactate and amino acids This can be explained as a result
of alcohol oxidation by the ADH reaction increasing the
amount of NADH relative to NAD in the cytolpasm.
Through the reaction catalysed by LDH, this will
reduce the availability of pyruvate, thereby
restricting its involvement in gluconeo- genesis.