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.

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 ProteinLipolysis

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