WEEK 5 (Monosaccharide Metabolism) Flashcards
Which Monosaccharides are isomers of Glucose?
Fructose & Galactose
Which monosaccharides make up Sucrose and Lactose?
SUCROSE = GLUCOSE + FRUCTOSE
LACTOSE = GLUCOSE + GALACTOSE
Galactose and Glucose are taken up by which transporter?
SGLT1 which is a Na+ dependent transporter
Fructose is taken up by which transporter?
GLUT 5 by Facilitated diffusion
How do Galactose, Glucose & Fructose leave enterocytes?
By GLUT 2
What is Fructose?
A Ketohexose found in honey and a wide variety of fruits and vegetables
Describe Fructose Metabolism
1) FRUCTOSE -> FRUCTOSE-1-PHOSPHATE via FRUCTOKINASE (use of an ATP)
2) FRUCTOSE-1-PHOSPHATE -> DIHYDROXYACETONE PHOSPHATE + GLYCERALDEHYDE via ALDOLASE B
3) DIHYDROXYACETONE PHOSPHATE -> GLYCERALDEHYDE-3-PHOSPHATE via TRIOSE PHOSPHATE ISOMERASE or GLYCERALDEHYDE -> GLYCEROL (use of NADH) or GLYCERALDEHYDE -> GLYCERALDEHYDE-3-PHOSPHATE via TRIOSE KINASE (use of an ATP)
4) GLYCERALDEHYDE-3-PHOSPHATE -> GLYCOLYSIS
Why is the rate of fructose metabolism more rapid than that of glucose?
Triose phosphate production from FRUCTOSE-1-PHOSPHATE bypasses PHOSPHOFRUCTOKINASE-1 which is the major rate-limiting step in glycolysis
Describe the disease ‘Essential Fructosuria’
- Involves a defect in FRUCTOKINASE
- Autosomal recessive
- A BENIGN, ASYMPTOMATIC CONDITION since fructose is not trapped in cells
SYMPTOMS:
- Fructose appears in blood and urine
Describe the disease ‘Hereditary Fructose Intolerance’ aka Aldolase B Deficiency
An autosomal recessive disorder where patients lack the enzyme to break down FRUCTOSE-1-PHOSPHATE (ALDOLASE B)
SYMPTOMS:
- Hypoglycaemia, Seizures & vomiting after fructose ingestion
- Failure to thrive
- Liver and renal failure
- Hepatomegaly
TREATMENT:
Avoid fructose, sucrose & sorbitol
Fructose is the primary source of energy for ________________
Spermatozoa
Fructose can be produced from glucose via ____________ without using ATP
Sorbitol
What happens during hyperglycaemic states?
Excess glucose is shunted from the hexokinase/glycolysis pathway into another metabolic pathway -> Cells containing ALDOSE REDUCTASE convert glucose to SORBITOL which is converted to Fructose via SORBITOL DEHYDROGENASE
What happens during hyperglycaemic states?
Excess glucose is shunted from the hexokinase/glycolysis pathway into another metabolic pathway -> Cells containing ALDOSE REDUCTASE convert glucose to SORBITOL which is converted to Fructose via SORBITOL DEHYDROGENASE
What happens when organs lack Sorbitol dehydrogenase?
Sorbitol accumulates -> Excess sorbitol causes osmotic damage -> Changes seen in hyperglycaemic diabetic patients e.g diabetic cataracts, diabetic retinopathy, diabetic neuropathy & diabetic nephropathy
Most galactose ingested by humans is in the form of ______________
Lactose
How is lactose converted to glucose?
Lactose is hydrolysed to galactose and glucose by LACTASE located on the microvillar membrane of the small intestine -> Following absorption, galactose is transported to the LIVER where it is converted to glucose
What are the symptoms of lactase deficiency after ingestion of lactose?
- Diarrhoea
- Bloating
- Cramps
What happens if galactose accumulates in the blood?
Galactose is transferred to the lens where Galactose is converted to GALACTITOL via ALDOSE REDUCTASE -> Galactitol trapped in the lens causes swelling and cataracts
What can happen to galactose in the well-fed state?
Galactose can enter glycolysis or contribute to glycogen storage
Describe Galactose-1-Phosphate Uridyltransferase deficiency
An autosomal recessive disorder where there is an absence of galactose-1-phosphate uridyltransferase. Damage is caused by accumulation of toxic substances (e.g galactitol) & symptoms develop when infant begins feeding.
SYMPTOMS:
- Cataracts early in life
- Vomiting, diarrhoea following lactose ingestion
- Lethargy
- Liver damage
- Hyperbilirubinemia (a condition in which there is a build up of bilirubin in the blood, causing yellow discoloration of the eyes and skin, called jaundice)
- Mental retardation
COMPLICATIONS:
Can lead to E Coli sepsis in neonates
Describe Galactokinase deficiency
An autosomal recessive disorder where there is a deficiency in GALACTOKINASE which causes Galactose to be converted to GALACTITOL in the eye lens.
SYMPTOMS:
- Galactose appears in blood (GALACTOSEMIA) & urine (GALACTOSURIA)
- Cataracts in early life
What are cataracts?
Clouding of the eye lens that affects vision
Which enzymes are correlated to mild galactosemia and classic galactosemia?
MILD GALACTOSEMIA = GALACTOKINASE
CLASSIC GALACTOSEMIA = GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE
Where does Lactase function?
On the intestinal brush border to digest lactose
What does an insufficient lactase enzyme lead to?
Lactase enzyme deficiency -> No monosaccharides (Glucose + Galactose) -> Dietary lactose intolerance
What are the different Lactase deficiency types?
- PRIMARY
- SECONDARY
- CONGENITAL
What are the properties of Primary Lactase Deficiency
- Age-dependent decline after childhood
- Common in people of Asian, African or Native American descent
What are the properties of Secondary Lactase Deficiency?
- Autoimmune disease
- Loss of intestinal brush border due to gastroenteritis
What are the properties of Congenital Lactase Deficiency?
- Rare
- Due to defective gene
Describe Lactase deficiency
TESTING:
- Stool demonstrates decreased pH and breath shows increased hydrogen content with LACTOSE HYDROGEN BREATH TEST
- Intestinal biopsy reveals normal mucosa in patient with hereditary lactose intolerance
SYMPTOMS:
- Bloating
- Cramps
- Flatulence
- Osmotic diarrhoea
TREATMENT:
- Avoid dairy products/add lactase pills to diet
- Lactose-free milk
