The study of this metabolism is
allowed to characterize many
diseases where cell function is
working poorly
Thanks to this has been able to
explain some clinical and
pathological situations where
enzymes play an important
role for organs and tissues
The illness + Metabolic
In 1908 Archibald Garrod
Determined the diagnosis on diseases caused by absence of
enzymes
Brings serious consequences like phenylketonuria, affects
1 of every 10000 humans
Diagnosis of an inherited metabolic disorder may involve measuring the activity of a given enzyme in a
sample taken from accessible tissue such as blood cells
In the metabolic pathway shown in Scheme 1, product X is synthesized from substrate A by a series of
enzyme catalyzed reactions. Furthermore, A can be metabolized to Z by a minor route, so that usually
only a small amount of Z
Jaundice
is due toExcessive amount of bilirubin
Macrophages phagocytes Metabolizes hemoglobin and
forms bilirubin
If it rises to 0.5 mm or more it is jaundice
Frequent in bone marrow,
Spleen
Liver
Import metabolic reaction catalyzed
by a specific transferase enzyme
Skin and whites of the eyes turn yellowish A newborn can
present the symptoms of this disease since the enzyme
transferase does not develop from birth
FREE RADICALS
Decompose pathogens and kill foreign organisms
Molecular entities containing
unpaired electrons which makes
them reactive This unpaired electron
makes the molecule a reactive
species Can be stabilized by donating
or removing electrons from other
molecules New radicals are generated
and thus a chain reaction is made
Causal agent of diseases such as
Cancer
inflamatory bowel disease
kwashiorkor
myocardical infraction
parkinson’s and disease rheumatoid arthritis
Macrophages, neutrophils, monocytes are phagocytic cells which are
involved in inflammation and infection Use free radicals as part of the
body's defense mechanism The high activity of these free extracellularly
free radicals and cause tissue injury
Highly
reactive
hydroxyl (OH)
Attacks biological molecules and initiates
chain reactions and damages cell
membranes and DNA thus increasing the risk
of developing cáncer
Superoxide (O) less toxic
and are generated by
metabolic reactions
Involve electron-controlled motion So The
mitochondria reduces the oxygen through the chain
of transport of electrons of the water which is made
through the action of an enzyme
ANTIOXIDANTS
Cells and tissues have a number of protective
mechanisms to combat free radicals and eliminate
them called the antioxidant defense system
Can restrict the damage of these to
the cells it is claimed that
antioxidants can cure such diseases
Glutathione (GSH) protects
proteins and membranes
against free radical attack
Enzimes
In the cell the enzyme
superoxide dismutase
removes superoxide by
catalyzing its conversion
into (H 2 O 2) which is
removed by catalase
Peptides
Vitamins
Vitamin E
(tocopherol)
Liposoluble antioxidant capable of preventing chain reactions, thus
avoiding irreparable damage to the membrane Acts by the
protection against oxidation of beta carotene lipoproteins (Protects
against heart disease and reduces the risk of various types of
cancer )
Vitamin C (ascorbic acid)
Acts as cofactor in
hydroxylation reactions
related to collagen
biosynthesis
Diabetes mellitus: A catabolic disease
is
Inability to control blood sugar levels
Disease
Hyperglycemia
Liever
In creased glucose production
by the liver and reduced
absorption by muscle and
adipose tissue
generate
Improves osmotically the excretion of water and stimulates thirst, giving the clasic symptoms of the disease
Kidney
The filtered glucose is normally completely reabsorbed, but
when blood glucose levels of 10mM are exceded,
reabsorption becomes satured and glucose appears in the
urine
Diagnostic test
Bliid sugar measurement
Is performed
After two hours of eating carbohydrates
Characteristics
High glucose leaves above
Hormones involved
insulin
Reduces blood glucose and its
storage as glycogen, aslo inhbits the
production of hepatic glucose by
glocagon
In diabetes there is ambalance of these hormones
Glucagon
Increase of glucose in blood by its
action on the liver, stimulating the
degradation of glycogen and
potentiating the glocogeonesis of the
proteins
Insulin deficiency
process
Insulin is anabolic and that coordinates the metabolic
processes in a number of body tissues
generate
A rapid mobilization of fatty acid from
adipose tissues, which are absorbed by the
liver and converted into ketosis in large
quantites accurs in terminal stoges of
diabetes when gloconeogesis is also
increased
The glucose of the aminoacids is
synthesized to begin the loss of urinary
excretion and to maintain higt levels of
sugar in blees so that glucose is used in the
absene of insulin
consequences
The excretion of ketone bodies in
the urine represents waste of
energy, loss of cations, blood loss
pH, diabetic coma that can cause
death
Types of diabetes
Neonatal
Insulin- dependent diabetes millitus, IDDM
Children and youth
Can be generated for
several years and the cell
b of the pancreas destory
so that no insulin is
produced
The treatment is the application of insulin
Diet and drugs sulfurine-lureas
Middle ages
Non insulin- dependent diabetes
millitus, NIDDM
Normal insulin levels
Hormone-sensitive cells that cause receptor malfunction
Less serious, more common
Atherosclerosis
is a disease that causes hardening and narrowing of the arteries
Coronary Arteries - Feed the Cardiac Muscle
Can produce a heart attack (it is the leading cause of death in Western societies)
4. Is due to the thickening of cholesterol deposits in the arterial wall
example
Cholesterol is a lipid molecule, an essential element for plasma menbranas
and for the synthesis of bile salts by the liver and steroid hormones
By their insolubility have to be transported by the
blood as proteins called low intensity lipoproteins
(LDL)
The L D L particle is a sphere with a single hydrophobic
protector called apoprotein B embedded in a nonpolar
cholesterol core, which is bound to long chain fatty acids to
form cholesterol esters.
LDL
The thickening of the walls is
associated with particles originating
from LDL
Has fatty acids where saturated
polium is found that it is attacked
by oxygen where free radicals are
formed
When LDL is oxidized it produces
elements that can be toxic to the
walls of the arteries
liver disease
liver disease
metanol in the liver is mateabolized in two ways
cytochrome P-450
oxidize the etanol
Enzyme alcohol dehydrogenase
treatment
is a complex treatment
since licor generates dependency
is treated with disulfram as form of aversion theraphy
disulfiram inhibits the ALDH by making the liquor somewhat unpleasant when consumed
anger: a usurper of intestinal metabolism
mecanisms of action
the vibrios colonize,adhere and secrete an exotoxim called cholerajen
this alerts the metabolism of mocous cells
and then toxin afects other tissuses
BACTERIUM:
vibrio cholerae
there was time
when tha
bacterium
caused
considerable
anatomical
damage to tha
intestinal
ephitelium