Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

METABOLISM OF MONOSACCHARIDES AND DISACCHARIDES
OVERVIEW




Glucose = most common monosaccharide
Other monosaccharides = fructose and galactose (found primarily in disaccharides)
Galactose = important component of structural carbohydrates

FRUCTOSE METABOLISM





Western diet  10% calories = fructose (55g/day)
Major source of fructose = sucrose (cleaved in intestine releasing glucose and fructose)
Fructose also found as a free monosaccharide in many fruits, honey, high-fructose corn syrup
Fructose transport into cells is insulin independent (fructose does not promote insulin secretion)

1) PHOSPHORYLATION OF FRUCTOSE






Fructose must be phosphorylated before entering the pathways of intermediary metabolism
Phosphorylation can be accomplished by either hexokinase or fructokinase
Hexokinase has a low affinity (high Michaelis constant K m) for fructose
Fructokinase has a low Km and high V max for fructose, therefore, it provides primary mechanism
for fructose phosphorylation
In liver, kidney, mucosa of small intestine, fructose + ATP  fructokinase  fructose 1phosphate + ADP

2) CLEAVAGE OF FRUCTOSE 1-PHOSPHATE


Fructose 1-phosphate  aldolase B (fructose 1-phosphate aldolase)  DHAP +

glyceraldehyde



DHAP directly enter glycolysis or gluconeogenesis
Glyceraldehyde can be metabolized by a number of pathways

Humans express three aldolases, A, B and C, the products of three different genes
...


3) KINETICS OF FRUCTOSE METABOLISM


Rate of fructose metabolism more rapid than that of glucose because trioses formed bypass
PFK-1, major rate-limiting step in glycolysis

4) DISORDERS OF FRUCTOSE METABOLISM
ESSENTIAL FRUCTOSURIA
 Lack of fructokinase
 Autosomal recessive (1:130,000 births)
 Benign condition
 Fructose accumulation in urine

HEREDITARY FRUCTOSE INTOLERANCE (HFI)
 Autosomal recessive (1:20,000 births)
 Absence of aldolase B leads to intracellular trapping of fructose 1-phosphate
 Severe disturbance of liver and kidney metabolism
 First symptoms appear when baby is weaned from milk and begins to be fed food containing
fructose or sucrose
 ↑ fructose 1-phosphate  ↓Pi  ↓ATP  ↑AMP  AMP degraded  ↑uric acid in
blood (hyperuricemia) and lactic acidosis
 ↓hepatic ATP  ↓gluconeogenesis  hypoglycemia and vomiting
 ↓hepatic ATP  ↓protein synthesis  ↓blood clotting factors
 ↓Pi  ↓glycogenolysis
 Diagnosis: fructose in urine, enzyme essay using liver cells, DNA-based testing
...

 Fructose, sucrose and sorbitol can cause hepatic failure and death
 Treatment: removal of fructose and sucrose from diet

5) CONVERSION OF MANNOSE TO FRUCTOSE 6-PHOSPHATE



Mannose = C-2 epimer of glucose and an important component of glycoproteins
Mannose  hexokinase  mannose 6-phosphate  phosphomannose isomerase  fructose 6phosphate

6) CONVERSION OF GLUCOSE TO FRUCTOSE VIA SORBITOL















Alternate mechanism for metabolizing a monosaccharide is to convert it into a polyol (sugar
alcohol) by the reduction of an aldehyde group, thereby producing an additional hydroxyl group
Glucose  aldose reductase  sorbitol (glucitol)
Aldose reductase found in lens, retina, Schwann cells, liver, kidney, placenta, RBCs, ovaries and
seminal vesicles
Sorbitol  sorbitol dehydrogenase  fructose
sorbitol dehydrogenase found in liver, ovaries and seminal vesicles
pathway from glucose to fructose in seminal vesicles benefits sperm cells, which use fructose as
a major carbohydrate energy source
Pathway from sorbitol to fructose in liver provides a mechanism by which any available sorbitol
is converted into a substance that can enter glycolysis or gluneogenesis
Effect of hyperglycemia on sorbitol metabolism
In lens, retina, nerve cells, and kidney, insulin is not required for the entry of glucose into cells
...

In tissues other than lactating mammary gland, protein A (β-D-galactosyltransferase) transfers
galactose from UDP-galactose to N-acetyl-D-glucosamine, producing N-acetyllactosamine



In lactating mammary gland, protein B (α-lactalbumin) stimulated by prolactin, forms a complex
with protein A, changing the specificity of that transferase so that lactose, rather than Nacetyllactosamine, is produced



---