Metabolism of monosaccharides & disaccharides

Question 1

What are the 2 main enzymes involved in fructose metabolism?

Answer 1

Fructokinase (traping)
Aldolase B

Question 2

Fructose is absorbed by what transporter in the GI tract?

Answer 2

GLUT 5

Question 3

Sucrase breaks sucrose into :

Disaccharides on brush border of intestine.

Answer 3

Gluctose & fructose

Question 4

What is the molecule derived from fructose that makes it traped in the cytoplasm?

Answer 4

Fructose-1-phosphtae

Question 5

Aldolase B cleaves fructose-1-phosphate into :

Answer 5

DHAP
Glyceraldehyde

Can then go to glycolysis, glycogenesis and gluconeogenesis

Equal affinity for fructose-1-phosphate & fructose 1,6 bisphosphate
Only enzyme which has affinity for both
Present in the liver, kidney & RBCs.

Question 6

Which sugar is transported into cells without depending on insulin ?

Answer 6

Fructose

Question 7

What is the form of fructose our body can metabolize.

Answer 7

D-fructose

Question 8

What is essential fructosuria ?

Answer 8

Deficiency of fructokinase leads to a clinically benign condition characterized by incomplete metabolism of fructose in the liver, leading to its excretion in the urine.

Why is it benign ?
Metabolized partly by hexokinase
No buildup in the body so no toxicity
Mostly asx

Question 9

Aldolase B deficiency leads to what condition ?

Answer 9

Hereditary fructose intolerance

Question 10

The rate of fructose metabolism is more rapid than that of glucose because the the trioses from fructose-1-phosphate bypasses which rate limiting enzyme of glycolysis ?

Answer 10

PFK-1

Question 11

Affinity of hexokinase to fructose is ?

Answer 11

Low

It can, to a small extent, transform D fructose back to fructose-6-phosphate.

Question 12

Fructose in urine will be found in what conditions?

Answer 12

Both essential fructosuria & hereditary fructose intolerance.

In hereditary fructose intolerance, inhibition of glycolysis leads to accumulation of fructose in the blood which is flushed in urine.

Question 13

Pathophysiology of hereditary fructose intolerance?

Answer 13

Trapping of phosphate in context of Aldose B def.

Fructose1-phosphate is trapped and builds up in the CYTOSOL. This is trapped with phosphate molecules which will lead to depletion of body phosphate pool.
Low ATP results. 30 min after ingesting fructose or sucrose, baby presents with vomiting, hypoglycemia (tremors, seizures, diaphoresis), lethargy. Lack of ATP will lead to inhibition of glycogenolysis, **gluconeogenesis **& glycolysis. You need to phosphorylate enzymes to undergo these processes. As ATP falls, AMP rises and is degraded causing hyperuricemia and lactic acidosis in addition to the fructosuria. Severe hypoglycemia results from lack of ATP to undergo gluconeogenesis which is essential for babies as they have low glycogen stores.
Potentially life threatening. Aldose B deficiency is part of the newborn screening panel and can also be dx.

Question 14

What is the trx for aldolase B deficiency?

Answer 14

Elimination of dietary Fructose &
Sucrose

Fruits, honey, high fructose corn syrup, sucrose drinks…

Question 15

Alternative method to metabolize monosaccharides is to convert it to :

Answer 15

Polyol *sugar alcohol

Question 16

Aldose reductase role:

Answer 16

Reduces sugars like glucose into their alcohol form : sorbitol.

This enzyme is present in MOST tissues.

Question 17

Fructose can be made from what other molecule in our body making it not essential in the diet ?

Answer 17

Glucose

Sperm cells need fructose to function but we don’t need it in our diet. We can physiologically make it from glucose.

Question 18

Glucose –> Sorbitol by :

Answer 18

Aldose reductase

Trapped as sorbitol due to addition of OH group.

This enzyme is present almost everywhere.

Question 19

Sorbitol –>fructose

Answer 19

Sorbitol dehydrogenase

This enzyme is present only in tissues that require fructose for their survival, such as sperm cells.

Question 20

Insulin is required to make glucose enter cells in what 2 tissues ?

Answer 20

Muscle
Adipose tissue

Question 21

Long term hyperglycemia, such as in uncontrolled diabetes leads to what complications?

Answer 21

Retinopathy and subsequently cataracts
Nephropathy
Peripheral neuropathy

Absence of sorbitol dehydrogenase in most tissues (lens, kidneys, nerves) and quick oversaturation of this enzyme if present leads to these complications. Sorbitol accumulates and these osmotically active substrates will attract a lot of water (pressure).

Question 22

Aldose reductase is induced by ?

Answer 22

Glucose

Present everywhere + inducible.

Question 23

Cataracts pathophysiology :

Answer 23

Aldose reductase will be increased
Sorbitol dehydrogenase decreased

Aldose reductase induced a lot due to overflow of glucose, lots of sorbitol formed, but no sorbitol dehydrogenase, so sorbitol builds up. *Only in specific tissues that lack that sorbitol dehydrogenase.

Question 24

Galactose –> Galactose-1-phosphate catalyzed by what enzyme ?

Answer 24

Galactokinase

Question 25

Galactose-1-phosphate cannot enter the glycolytic pathway unless it is first converted to UDP-galactose by :

Answer 25

GALT

Galactose 1-phosphate uridylyl transferase

Question 26

Galactose does not directly enter glycolysis, it first gets stored as glycogen via what process before being broken down into glucose and entering glycolysis?

Answer 26

Glycogenesis

Question 27

Glucose and galactose are

Answer 27

C4 epimers

Question 28

Galactokinase deficiency

Answer 28

Causes galactosemia and galactosuria due to galactitol (alcohol form) in the response to î aldose reductase activity when galactose builds up.

Presents as early after first few days on life, when baby is breast feeding.
It is benign everywhere, except in the lens. No systemic manifesatations, cataract may be the only manifestation.

Question 29

Cataracts formation linked with elevation in what enzyme in all cases ?

Answer 29

Elevated aldose reductase is common to both however the products that accumulate are different, either sorbitol or galactitol.

Question 30

Why is there no link with excess fructose and cataracts ?

Answer 30

Its a ketone sugar (it cannot induce aldose redutase- no polyol accumulation).

Question 31

Severe galactose metabolic disorder ?

Answer 31

Classic galactosemia

Absence of GALT enzyme results in accumulation of galactose-1-phosphate, a toxic metabolite that causes hepatic and renal dysfunction. Symptoms will start as early as neonatal period, with vomiting, lethargy, jaundice and failure to thrive.

Question 32

Why does classic galactosemia cause cataracts ?

Answer 32

Galactose-1-phosphate is trapped in cells, with ATP. No more ATP to trap further galactose molecules coming in the body, so eventually will back up in the blood which will induce aldose reductase enzyme to convert excess galactose into Galactitol –> cataracts.

Question 33

Excess galactose also spills in the urine and causes it to test positive for :

Answer 33

Reducing susbstance
Clini-test positive (dipstick)

Will be positive for all fructosuria, glucosuria & galactosuria as well

Reducing sugars : have free aldehyde or free keto group (usually all monosaccharides & disaccharides except sucrose*).
Non-reducing : aldehyl or keto group involved in bond formation (just sucrose).

Question 34

You can still make lactose without exogenous galactose via :

E.g. in a case of galatosemic mother who is nursing, can she still make galactose so the baby gets it via breast feeding?

Answer 34

Epimerization reaction
Converts glucose in diet to galactose

Question 35

Galactose—-> galactitiol catalyzed by ?

Answer 35

Aldose reductase