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PATHOPHYSIOLOGY

OF CARBOHYDRATEMETABOLISM

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Lactase intolerance

lactase = enzyme which splits disaccharide lactose(to glucose and galactose)

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Pathomechanisms

a) Activity of lactase is decreaseddecreased hydrolysis of

disaccharidedecreased resorbtion of substrateincreasedconcentration of disaccharide in small intestine lumenincreased osmotic activity of the lumen fluiddiarrhea

b)Activity of lactase is decreasedincreased concentration ofdisaccharide in small intestine lumen increased concentrationof disaccharide in large intestinedisaccharide fermentationby bacteriaincreased concentration of lactic acid and fattyacids stimulation of intestine wall abdominal cramps,

bloating, diarrhea, acidic stools, explosive diarrhea

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Lactase deficiency syndrome

Causes of lactase deficiency:- genetic defect (primary)

- secondary to a wide variety of gastrointestinal diseases

that damage the mucosa of the small intestine (secondary)

- Milk intolerance may not become clinically apparent until

adolescence

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Causes of secondary lactase deficiency:- nontropical (celiac disease)/ tropical sprue,

- regional enteritis,

- viral and bacterial infections of the intestinal tract,- giardiasis, cystic fibrosis, ulcerative colitis

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Glycogenosis (glycogen storage disease)

Autosomal recessive disease (inborn errors of metabolism,enzymopathy)

There are defects in degradation of glycogen.

The disturbances result in storage of abnormal glycogen,or storage of abnormal amount of glycogen in variousorgans of the body

Example: Hepatorenal glycogenosis (Morbus von Gierke)

Cause: Deficit of glucose-6-phosphatase in liver and kidneyResults: Hypoglycemia in fasting individuals

There are 9 other types of glycogenosis

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Glycogen Storage

Diseases are genetic

enzyme deficiencies

associated with excessive

glycogen accumulation

within cells.Some enzymes whose

deficiency leads to

glycogen accumulation

are part of the inter-connected pathways

shown here.

glycogen

glucose-1-P

Glucose-6-Phosphatase

glucose-6-P glucose + Pi

fructose-6-P

Phosphofructokinase

fructose-1,6-bisP

Glycolysis continued

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Symptoms in addition to excess glycogen storage:

When a genetic defect affects mainly an isoform of an

enzyme expressed in liver, a common symptom is

hypoglycemia, relating to impaired mobilization of

glucose for release to the blood during fasting.

When the defect is in muscle tissue, weakness &

difficulty with exercise result from inability to

increase glucose entry into Glycolysis during exercise.

Additional symptoms depend on the particular

enzyme that is deficient.

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Glycogen Storage DiseaseSymptoms, in addition to

glycogen accumulation

Type I, liver deficiency of

Glucose-6-phosphatase (von

Gierke's disease)

hypoglycemia (low blood

glucose) when fasting, liver

enlargement.

Type IV, deficiency of

branching enzyme in variousorgans, including liver

(Andersen's disease)

liver dysfunction and early

death.

Type V, muscle deficiency of

Glycogen Phosphorylase(McArdle's disease)

muscle cramps with exercise.

Type VII, muscle deficiency of

Phosphofructokinase.

inability to exercise.

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Galactosemia

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Galactosemia

* characteristics galactosemiaaffects thebodys ability toprocessgalactose (a

sugar found indairy products)

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Activation of Galactose

O

CH2OH

HOH

H OH

H

H

OH

H

OPO3=

O

CH2OH

HH

OHOH

H

H

OH

H

O P O

O

O

P O

O

O

Uridine

O

CH2OH

HOH

HOH

H

H

OH

H

O P O

O

O

P O

O

O

Uridine

UMP

Galactose-1-P

Galactose-1-PUridylyl Transferase

UDP-Glucose

Glucose-1-P

UDP-Galactose

Glucose-6-P

Phosphoglucomutase

Glycolysis

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Mode of Inheritance

* galactosemia autosomalrecessive (a child

has to inherit onegene from eachparent that is

defective)* Galt gene is on

chromosome 9

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Symptoms of Galactosemia

* symptoms: kidneyfailure, fine and

gross motor skilldelays, poorgrowth, and mentalretardation (all as

a result of thegalactose build-up)

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Detection of Galactosemia

* galactosemia appears in approximately

1 in every 30,000 live births and can

be detected by a blood test

* galactosemia is a universal genetic

disorder everyone has equal chancesof getting it

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Prognosis

if untreated, 75% of all infants withgalactosemia may die

galactosemia is treatable

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Additional Health Problems

galactosemia isn't usually lifethreatening

the common health problems include:hypoglycemia, cataracts, learningdisabilities, poor growth, and speechdisorders

Cataract development due to galactitol(dulcitol)

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Treatment

the only way to treat galactosemia isby changing one's diet

people with galactosemia need to stayaway from all foods and drinks thathave galactose (ex: milk, cheese,legumes, which are pods like peas or

beans)