Tishk International University
Faculty of Science
Department of Medical Analysis
General and systemic Biochemistry
Carbohydrate Metabolism
Dr. Rundk A. Hwaiz
Grade 2-Fall 2020-2021
Dr. Rundk A. Hwaiz
Carbohydrate metabolism
It is important because 65% of our food is carbohydrates, like
polysaccharides (rice),
disaccharides (milk) and monosacharides (table sugar)
Monosaccharide no need for digestion, it directly absorbed
into the blood.
The first step in carbohydrate metabolism start with digestion
1. Digestion
• digestion: is break down of polysaccharides which start in the mouth by enzyme
called salivary amylase.
• Salivary amylase breaks down the alpha 1,4 glycosidic linkage in the mouth.
• There is another type of amylase which called pancreatic amylase which is
responsible for breaking down the rest of polysaccharide which didn’t broken in
the mouth because we can not chew the food for long time in the mouth. So the
continouation of the breaking down of polysaccharides to disaccharides occur in
the intestine.
• The proper condition for amylases are slightly alkaline condition pH between 6.7 to
7.1 and presence of Cl ion. The Chloride ion is a cofactor which make the reaction
occur faster.
• In the stomach the action of salivary amylase will stop because the pH of stomach
is acidic.
Once all polysaccharides converts to disaccharides by amylase,
disaccharides will convert to monosaccharides by disaccharidases like
(maltase, sucrase and lactase to break down maltose, sucrose and
lactose respectively)
Maltose convert to two unit of glucose by maltase.
Sucruse convrt to one glucose and one fructose by sucrase.
Lactose wil convert to one glucose and galactose by lactase.
Glucose, galactose an fructose are monosaccharides and they are ready
for absorption into the blood via intestinal cells.
Lactose intolerance
Is the clinical condition that occur as a result for lactase enzyme
deffeciency . Lactase is rsponsible for breaking down lactose to glucose
and galactose.
The patients with this condition, lack lactase enzyme for two reason:
1. Genetic
2. acquired.
Genetic (gene deletion from born)
Acqiured because of frequent intestinal inflammation, which may lead to
deceasing the lactase enzyme comparing by healthy individual.
In babies who are the main food for them is milk which contaion lactose,
become sick and irritated and don’t get advantages from the milk
because there will be no digestion and therefore no absorption so the
baby will not get energy and lose wight. In addition the baby feel pain
and cramps because the accumulated undigested lactose in intestine
which can be food for bacteria flora and that cause gases and abdominal
cramps.
Treatment for genetic lactose intolerance is free lactose diet.
For those patients who have acquired lactose intolerance, they need to
decrease the ingestion of products that contain lactose.
2. Absorption: means the transfere of nutrients from lumen into the blood.
Fructose absorbs passively into the cells via GLUT5 and then absorbs into the blood via GLUT2
Galactose absorbs actively into the cells via SGLT1 and then absorbs into the blood via GLUT2
Glucose absorbs passively into the cells via GLUT5 and then absorbs into the blood via GLUT2
in case of low blood glucose.
Glucose absorbs actively into the cells via SGLT1 and then absorbs into the blood via GLUT2 in
case of normal or low blood glucose.
Glucose, galactose and fructose are alcohols and they are polar thererefore need carrier which
made of proteins to cross them into the lipid bilayer of cell membranes.
Glucose carriers
Na dependent Na independent
Insulin dependent Insulin independent
GLUT4 GLUT1
GLUT2
GLUT3
GLUT5
GLUT7
SGLT1
SGLT2
SGLT1: found in the brush boarder (lumen) of intestine responsible for glucose uptake
in the intestine.
SGLT2: found in the proximal convuluted tubule of kidney, responsible for glucose
reabsorption in the kidney.
GLUT4: found in the muscle and adipose tissue, responsible of glucose uptake and it is
insulin dependent carrier.
GLUT1: found in the brain and RBC
GLUT2: found in the basal membrane of intestine
GLUT3: found in the brain
GLUT5: Found in the brush boarder of intestine.
GLUT7: found in the hepatocytes (liver cells)
The higher the body weight the higher glucose absorption. The body can absorb
1gm/Kg/h.
Fate of absorbed glucose
1. Oxidation: to obtain energy by glycolysis pathway and
krebs cycle to generate ATP
2. Storage: as a form of glycogen stored in the liver and
muscle. The extra glucose stores as lipid in adepocytes.
3. Excretion: in the normal and healthy condition there will
not be any excretion of glcose via urin, but under specific
condition like diabetes and kidney failure there will be
excretion of glucose via urin.
Glycolysis
Definition: is a process of break down of glucose to get energy.
Site: it occur in the cytosole of every cell in the body.
Function: to produce energy for the cells.
Steps: •There are total 4 ATP, 2 ATP consumed in the first five
steps.
So the net ATP in glycolysis is (4-2= 2 ATP)
•There will be 2 NADH produced as well which can give 6
ATP but they need mitochondria and oxygen to enter
electrontransport chain to supply ATP.
In the absence of ogygen NADH+H converts to NAD in the reaction of
conversion of pyruvate to lactate for exampl in cells which lack
mitochondria like RBC.
Pyruvate Lactate
NADH+H NAD
Lactate dehydrogenase
The end product of an aerobic process (lack of oxygen and
mitochondria) is lactate
The end product of aerobic process (in presence of oxygen and
mitochondria) is pyruvate which convert to oxaloacetate to enter krebs
cycle.
Regulation: the regulation of glycolysis depend on hormones,
insulin and anti insulin (glucagon, epinephrine and nor
epinephrine)
Regulation of enzymes involved in glycolysis
During feeding state insulin is dominant.
During fasting state glucagone is dominant.
Clinical significance of glycolysis
There are cells which does not have mitochondria like RBC, the energy
source for RBC is via glycolysis pathway.
In the absence of one of enzymes that involved in glycolysis, may lead to
energy defeciency for RBCs and that lead to distruction of them because
of lack of ATP and this condition called metabolic haemolytic anemia.
Tishk International University
Faculty of Science
Department of Medical Analysis
General and systemic Biochemistry
Carbohydrate Metabolism
Dr. Rundk A. Hwaiz
Grade 2-Fall 2020-2021
Dr. Rundk A. Hwaiz
Kreb’s cycle:
Definition: Is complete oxidation of Acetyle CoA into carbon
dioxide, whatever the source of acetyle CoA like carbohydrate,
lipid or protein.
Site: Inside mitochondria and need oxygen so any tissue have
mitochondria are able to produce ATP via krebs cycle.
Function: The main function is to supply ATP, 12 ATP per
cycle or per acetyle CoA. In addition Krebs cycle is
Amphibolic.
Steps:
Isocitrate
dehydrogenase
Succinate
dehydrogenase
Citrate
Synthase
aconitase
Fumarase
Α-ketoglutarate
dehydrogenase
Succinate
thiokinase
GTP GDP
Malate
Dehydrogenase
NADH+H=3ATP
FADH2=2ATP
GTP=ATP
Krebs cycle considered Amphibolic, why?
Amphibolic means Krebs cycle is both catabolic and anabolic.
Why Catabolic is breaking down. It breaks down Acetyle CoA into
carbon dioxide (CO2). This reaction or oxidation occur in both isocitrate
dehydrogenase reaction and alpha ketoglutarate dehydrogenase reaction.
Why Anabolic: because the substrates in krebs cycle are intermediate
(precursor) for other molecules for ex: citrate can produce fat. Alpha
ketoglutarate can synthesise amino acids like glutamate and glutamine.
Succinyle can synthesise haem. Oxaloacitate can synthesise amino acids
like aspartate and aspargine.
Hexose Mono Phosphate Shunt (HMP Shunt)
Definition: Is an alternative pathway to glycolysis and Krebs cycle for
glucose oxidation in which it does not gain ATP but instead it generates
Ribose 5 Phosphate and NADPH+H.
Site and Function: it occure in cytoplasm of following tissues: Liver,
adipose tissue, lactating mammary gland, testes and ovaries, adrenal
glands, RBCs and muscles.
It occure in liver, adipose tissue and mammary glands adrenal gland,
testes and ovaries because NADPH is the main source of fat synthesis
and cholesterol synthesis and cholesterol is precurser of all steroid
hormones like glucocorticoid, mineralocorticoid and sex hormones.
The major source of NADPH is HMP shunt.
It occur in muscles because muscles need high amount of Ribose 5
Phosphate. R5P is important in muscle because muscle needs to much
DNA and RNA. Ribose 5 phosphate is the major source of purine and
pyrimidine bases (to synthesise nucleotides). In addition muscles need
energy and energy needs carriers like NAD and FAD, in which they
contain R5P.
NADPH also protect RBC’s from oxidative stress.
Steps:
Clinical significance:
G6PDH deficiency lead
to haemolytic anemia.
Glycogen metabolism
1. Glycogenesis:
Definition
Site
function
Steps
Definition: Synthesis of glycogen from excess amount of
glucose.
Site: It occur in cytoplasm of most of the tissues but mostly in
liver and muscles.
Function: Is storage of excess glucose.
Steps:
2. Glycogenolysis:
Definition
Site
Function
Regulation
Steps
Glycogen storage diseases
Definition: Breakdown of glycogen into glucose.
Site: it occur in cytoplasm mainly in liver and muscles.
Function: function of glycogenolysis in liver is to maintain
glucose level during fasting state for about 16-18h. In muscle
the glycogenolysis is to supply energy to muscle during
muscular contraction.
Hormonal regulation of glycogen synthesis:
During feed state, Insulin stimulate glycogenesis and inhibit
glycogenolysis. During fasting state, anti insulin hormones
inhibit glycogenesis and stimulate glycogenesis by affecting
enzyme.
Steps:
Glycogen storage diseases:
Von geark’s disease
Anderson disease
Cori’s disease
Mc Ardle’s disease
3. Gluconeogenesis:
Definition
Site
Function
Steps
Regulation
Substrates
Definition: It is synthesis of glucose by non carbohydrate
source.
Site: it occur in cytoplasm and mitochondria of liver and to
small extent occur in kidneys.
Function: To get rid of waste product and maintain the glucose
level in blood for more than 18h fasting because glucose is
the main source of energy for some tissues like brain and
RBC.
Steps:
Glycolysis Gluconeogenesis
Regulation:
Insulin inhibit gluconeogenesis and anti insulin stimulate
Gluconeogenesis.
Glucocorticoid stimulate gluconeogenesis, why?
We need substrate to make glucose like pyruvate, lactate, some time
amino acids. Cortisol or glucocorticoid will increase the
substrates for gluconeogenesis, because clucocorticoid is
catabolic hormone which breaks down biomolecules and when
these biomolecules break down, the supply amino acid, fatty
acids, lactate, pyruvate or glycerol which enter gluconeogenesis
Substrates:
Lactate or pyruvate
Glycerol
Odd chain fatty acids
Cori Cycle
Alanine Cycle
Galactose metabolism
Clinical condition related to galactose metabolism
Galactosemia: is the condition that characterize by high
concentration of galactose in the blood followed by
galactosurea, the presence of galactose in the urine. This
condition caused by the lack of enzyme that convert galactose
to glucose, and there are no pathways to deal with galactose in
the body. The main problem is the defect in the galactose
1phosphate Uridyle transferase enzyme and to minor extent
may be defect in galactokinase enzyme.
Fructose Metabolism
Regulation of blood glucose
Blood glucose normal ranges
Fasting: 70-110 mg/dl
1h postparandial: 140-150 mg/dl
2h postparandial: 70-140 mg/dl
Source of blood glucose
The first 2h after eating it comes from diet, from 16h-18h,
glucose comes from glycogen that stored in the liver by the
process liver glycogenolysis. After 18h, glucose comes from
gluconeogenesis that mainly occur in liver and to small extent
in kidney.
Role of organs and hormones in regulation of blood glucose
GIT
Liver
Kidney
Muscles and adipose tissue
Hyperglycemia
Fasting blood glucose higher than 126 mg/dl.
Diabetes Mellitus.
Corticosteroids induction
Anti-insulin (Cushing syndrom)
Stress
Hypoglycemia
Fasting or postparandial blood glucose less than 45 mg/dl.
Glucosuria
Hyperglycemia Normoglycemia
Diabetes Mellitus
Is a metabolic syndrome that characterized by hyperglycemia
and followed by symptoms, polyuria, polydepsia, polyphagis,
and undesired weight lose.
Types of DM:
Type 1 Diabetes
Type 2 Diabetes
Gestational Diabetes
Special types
Type 1 diabetes mellitus: it also called insulin dependent diabetes
mellitus.
10-20% of DM case are T1D
Auto immune disease, because of antibody attack islets of pancrease
that is responsible for insulin secretion.
Antibodies like ICA (islet cell antibody) means there are antibody
attack islet cells, GADA (glutamic acid decarboxylase antibody) it is
antibody against glutamic acid decarboxylase enzyme, IA (insulin
antibody) antibody against insulin.
If the patients have type 1 diabetes means no insulin but there are no
auto immune disease (no antibody) so in this case it is ideopathic type 1
diabetes.
Type 2 diabetes mellitus: it also called non-insulin dependent diabetes
mellitus.
80-90% of DM case are T2D
Obesety and family history are main risk factors
In the begning the patients have insulin resistance (the insulin receptors
doesnt respond to insulin) and this lead to hyperinsulinemia.
In the begning of the disease the islets of langerhanse secrete insulin
normaly but by passing times the pancreas become exausted and will not
secrete insulin any more so the patients will become insulin dependent,
means need to take insulin instead of oral hypoglycemic agents.
Gestational diabetes mellitus: when pregnant women first diagnosed with
hyperglycemia in the second or third trimester of pregnancy.
Special types of DM:
Monogenic Diabetes syndrom: Neonatal and MODY
Exocrine pancreatic disease
Drug induced
Metabolic disturbances
Insulin action
Glycolysis
Gluconeogenesis
Glycogenolysis
Glycogenesis
CHO Lipid Protein Lipolysis
Lipogenesis
Catabolism
Anabolism
Invistigation for diabetese mellitus
Normal Diabetic
FBS: 70-100 mg/dl equal or more than 126 mg/dl
PPBS: less than 140 mg/dl equal or more than 200 mg/dl
OGTT