Download Fractose and galactose Metabolism

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Fractose and galactose Metabolism
About 15% to 20% of the calories contained in
the western diet are supplied by fructose (about
100g/day). The major source of fructose is
Disacchariede sucrose (table sugar). Fructose is
also found as a free monosaccharide in many
fruits and vegetables and in honey. Entry of
fructose into cells is not insulin dependent.
Fructose is metabolized in the liver where it is
converted to pyruvate or under fasting
conditions to glucose.
In mild or treated diabetes, fructose is suitable
source of energy because its metabolism is
insulin-independent and the oxidation of
fructose via glycolysis and TCA cycle is favored.
In severe diabetes, the flux is towards the
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synthesis of glucose, and fructose instead of
being helpful will be detrimental to the patient.
In the eye lens, sorbitol synthesized from the
excess glucose may promote cataract
development.
Metabolism of galactose:
The major dietary source of galactose is the
disaccharide lactose found in milk or milk
products. Some galactose can also be obtained
by degradation of complex carbohydrates such
as glycoproteins and glycolipids, which are
important membrane components.
UDP-galactose may be reacting with glucose in
the mammary gland to produce the milk sugar
lactose.
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Galactosemia:
The appearance of high concentration of
galactose in the blood after lactose ingestion
may be due to galactokinase deficiency or to an
uridyl transferase deficiency. In both condition,
excess galactose may reduce to galactitol in
nerve tissue, lens, liver and kidney causing
severe liver damage, severe mental retardation
and cataract.
Babies with this deficiency have severe vomiting
and diarrhea.
Therapy: rapid diagnosis and removal of
galactose and lactose from the diet.
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The uridyl transferase deficiency is more severe,
causing elevation of galactose 1-p which inhibits
phosphoglucomutase, intering with glycogen
synthesis and degradation.
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Glycogen Metabolism
Glycogen is large, branched polymer consisting
of D-glucose residues. The linkage between
glucose residues is α-1, 4 except at branch points
where the linkage is α-1, 6.
On the average, there is a branch every 8 to 10
residues.
Glycogen synthesis and
degradation :
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The fate of glucosyl units released from
glycogen:
In the liver, glycogen is degraded to maintain
blood glucose. Glucose-1-P is converted by
phosphoglucomutase to glucose-6-P. Inorganic
phosphate is released by glucose 6-phoaphatse,
and free glucose enters the blood.
In muscle, glycogen is degraded to provide
energy for contraction. Phosphoglucomutase
converts glucose-1-P to glucose-6-P, which
enters the pathway of glycolysis and is converted
either to lactate or to CO2 and H2O, generating
ATP.
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Remark:
Muscle does not contain glu-6-phosphatase.
Therefore, does not contribute to maintenance
of blood glucose.
Regulation of Glycogen stores:
Glucagon acts on liver cells and epinephrine
(adrenaline) acts on both liver and muscle cells
to stimulate glycogen degradation.
Glycogen degradation in liver
In liver, glucagon(during fasting) and
epinephrine(during exercise or stress) stimulate
glycogen breakdown. The free glucose that is
produced is used to maintain blood glucose
levels.
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Glycogen degradation in muscle
In muscle, epinephrine stimulate glycogen
breakdown to glu-1-P, which is converted to glu6-P, which enters glycolysis and generate ATP
for muscle contraction.
Remark:
Muscle does not breakdown glycogen in
response to glucagon.
Glycogen synthesis
Insulin, which is elevated after a meal,
stimulates the synthesis of glycogen in both liver
and muscle. Insulin stimulates the uptake of
glucose by muscle, providing increased
substrate for glycogen synthesis.
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Glucose metabolism and diabetes mellitus
Carbohydrate is digested to simple
monosaccharides which are then absorbed.
Starch provides glucose directly, while fructose(
from dietary sucrose) and galactose (from
dietary lactose) are absorbed and also converted
into glucose in the liver.
Glucose is the common carbohydrate currency
of the body.
Insulin
It is a small protein synthesized in the beta cells
of the islets of langerhans of the pancreas. It acts
through membrane receptors and its main
target tissues are liver, muscle and adipose
tissue.
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Action of insulin
Glucose can not enter the cells of most body
tissues in the absence of insulin. The effects of
insulin are opposed by other hormones,
glucagons, adrenaline, glucocorticoids and
growth hormone. The blood glucose
concentration is the result of a balance between
these different endocrine.
1- Insulin stimulate glucose uptake in muscle
and adipose tissue
2- Insulin stimulate glycolysis
3- Insulin stimulate glycogen synthesis
4- Insulin stimulate protein synthesis
5- Insulin stimulate uptake of ions (especially
K+ )
6- Insulin stop proteolysis
7- Insulin stop lipolysis
8- Insulin stop gluconeogensis
9- Insulin stop glycogenolysis
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Clinical Notes:
1- Diabetes
mellitus
It is defined as a syndrome characterized by
hyperglycemia due to an absolute or relative
lake of insulin and or insulin resistance.
Types of diabetes mellitus
A- Insulin-dependent
diabetes
mellitus
(IDDM), it is called type 1 may accounts
for 15% of all diagnosed cases of diabetes.
It can occur at any age but most common
in early teenage years (9-14 years). In type
1 the pancreas makes little or no insulin
due to autoimmune destruction of insulin
producing
β-cells,
genetic
and
environmental factors such as a viral
infection.
The presence of islet cell antibodies in serum
predicts future development of diabetes.
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B- Type 2 (NIDDM), may account for 85% of
all diagnosed cases of diabetes and most
often occurs in adult (40-80 years). Risk
factors for type 2 diabetes include older
age, obesity, and family history of diabetes.
In type 2 the insulin level may be normal
or
even
high.
Obesity
is
the
most
commonly associated clinical feature.
C- Gestational diabetes; It develops in 2 to
5% of all pregnancies but disappears when
a pregnancy is over. Women who have had
gestational diabetes are increased risk for
later developing type 2 diabetes. Nearly
40% of women with a history of gestational
diabetes develop diabetes in future.
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What are the symptoms of diabetes?
People who think they might have diabetes must
visit a physician for diagnosis. They might have
some or none of the following symptoms.
1- fatigue
2- polyuria (frequent urination)
3- polydipsia (excessive thirst)
4- polyphagia
5- blurred vision (retinopathy may lead to
blindness) or sudden vision changes.
6- Nephropathy leads to renal failure.
7- Weigh loss
8- Dry mouth and very dry skin
9- Sores that are slow to heal
10-
More infections than usual
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impotence
2- Galactosemia
The appearance of high concentration of
galactose in the blood after lactose ingestion
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may be due to galactokinase deficiency or to an
uridyl transferase deficiency. In both condition,
excess galactose may reduce to galactitol in
nerve tissue, lens, liver and kidney causing
severe liver damage, severe mental retardation
and cataract.
Babies with this deficiency have severe vomiting
and diarrhea.
Therapy: rapid diagnosis and removal of
galactose and lactose from the diet.
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The uridyl transferase deficiency is more
severe, causing elevation of galactose 1-p which
inhibits phosphoglucomutase, intering with
glycogen synthesis and degradation.
3- Essential fructosuria
Fructokinase is deficient, so fructose can not be
metabolized as rapidly as normal. Blood
fructose level rise and fructose may be
appearing in the urine. This condition is benign.
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Essential fructosuria results from a lack of
fructokinase in the liver.
Fructokinase is deficient, so fructose can not be
metabolized as rapidly as normal. Blood
fructose levels rise and fructose may appear in
the urine. This condition is benign.
4- Hereditary fructose intolerance (fructose
poisoning):
Absence of aldolase B lead to accumulates of
fructose 1-phosphate. Causes severe
hypoglycemia (inhibits glucose production) if
fructose is ingested, vomiting, jaundices, and
hemorrhage. Also, can cause hepatic failure.
Therapy: rapid detection and removal of
fructose and sucrose from the diet.
5- Phenyl Ketonuria (PKU)
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The reaction above, catalyzed by phenyl alanine
hydroxylase, It the first reaction in catabolism
of phenyl alanine. Deficiency of phenyl
hydroxylase, phenyl accumulates and it
converted to compound such as the phenyl
ketone, which give the urine a musty odor,
mental retardation, failure to walk or talk,
hyperactivity and failure to grow occurs. PKU is
treated by restriction of Phe in diet. The
complete neuralgic damage can be prevented.
Gluconeogenesis;
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Gluconeogenesis is the synthesis of glucose from
compounds that are not carbohydrate. It occurs
mainly in the liver.
In human, the major precursors for
gluconeogenesis are lactate, amino acids, and
glycerol, fatty acids do not produce any net
glucose.
It is important for the following reasons;
1- To maintain blood glucose concentration, and
provide energy for glucose- dependent tissues
(e.g. red blood cells, brain, and renal medulla).
2- Glucose is the source of glyceride glycerol in
the adipose tissue (because no glycerokinase in
adipose tissue, free glycerol can not be utilized
readily in this tissue for triacylglycerol
synthesis).
3- in the mammary gland, glucose is required
for lactose synthesis.
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4- The gluconeogenic pathway helps to clear
from the blood metabolic products of other
tissues (e.g. lactate produced by muscle and
RBC, and glycerol produced by adipose tissue).
Lipid Metabolism
Lipids are a heterogeneous group of organic
biomolecules soluble in non-polar solvents, such
as ether and benzene. Compounds that are
related.
Triacylglyceroles ( triglycerides):
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Triacylglycerols are esters of fatty acids and the
trihydroxy sugar alcohol glycerol.
Triglycerids, containing 9 calories per gram, are
obtained from the diet or are synthesized in the
liver after a meal. They are transported in the
blood as lipoproteins and stored in adipose
tissue.
The major class of blood lipoproteins include:
1- Chylomicrons.
2- VLDL (very low density lipoproteins)
3- IDL (intermediate density lipoproteins)
4- LDL (low density lipoproteins)
5- HDL (high density lipoproteins)
In addition to triglycerides they contain
proteins, phospholipids, cholesterol, and
cholesterol esters.
Of these lipoproteins, the highest triacylglycerol
(TG) concentrations are found in chylomicrons
and VLDL (85% and 60% of the total
composition respectively) and a much lower TG
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concentration is in LD and HDL (about 15% of
total).
45% of total composition of HDL is protein and
consider the highest among lipoproteins. While
chylomicrons and VLDL contains the lowest
amounts of protein. Lipoproteins function both
to keep lipids soluble as they transport them in
the plasma and for delivering their lipid
contents to the tissues.
In human, a gradual deposition of lipid,
especially cholesterol in tissues. When the lipid
deposition contributes to plaque formation,
causing the narrowing of blood vessels- a
condition known as atherosclerosis.
HDL particles are synthesized in the liver and
are released into the bloodstream.
Functions
HDL is excellent acceptors of unesterified
cholesterol from the surface of cell membranes
and from other circulating lipoproteins (HDL
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uptake of free cholesterol). Esterification of free
cholesterol.
During fasting, fatty acids, derived from adipose
triglyceride stores, can be oxidized to co2 and
H2O by various tissues, producing energy in the
form of ATP. In the liver during fasting, fatty
acids are converted to ketone bodies, which are
released into the blood, taken up by tissues such
as muscle and kidney, and oxidized.
Cholesterol metabolism:
Cholesterol is synthesized in most tissues of the
human body, where it serve as a component of
cell membrane. It produced mainly in the liver
and intestine.
In the liver, cholesterol may be converted to bile
salts.
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In endocrine tissues, cholesterol is may be
converted to steroid hormones.
A precursor of cholesterol may be converted by
a series of tissues to the active form of Vit D
Cholesterol is stored in tissues as cholesterol
esters and is transported in this form in the
blood lipoprotein, which also carry free
cholesterol.
All the carbons of cholesterol are derived from
acetyl co A
Q1:- Which are the hormones mainly concerned
in controlling the synthesis and degradation of
glycogen in muscle and liver?
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