Metabolism of other Mono-and Disaccharides Flashcards
fructose and galactose
- occur in significant amounts in the diet (primarily in disaccharides)
- make important contributions to energy metabolism
What is an important component of structural carbohydrates?
galactose
fructose
- significant source of calories (10%) in typical western diet
- comes from sucrose, high fructose corn syrup, honey, fruits
fructose entry into cells
NOT insulin dependent
fructose mediated by what transporter?
GLUT 5
fructose and insulin secretion
does not promote insulin secretion
fructose metabolization
Bypasses the PFK-1 step, which means that it is metabolized more rapidly than glucose
step 1 of fructose metabolism
- phosphorylation of fructose
- enzymes-fructokinase and hexokinase
- IRREVERSIBLE
fructokinase
- phosphorylation of fructose
- in liver (mostly), kidney, and small intestinal mucosal cells
- uses ATP
hexokinase
- phosphorylation of fructose
- high Km (low affinity) for fructose, therefore it does not usually contribute significantly
- acts in all other tissues
step 2 of fructose metabolism
- cleavage of fructose 1-phosphate
- enzyme: aldolase B
- DHAP and glyceraldehyde formed
DHAP
formed from the cleavage of fructose 1-P with enzyme Aldolase B
can directly enter glycolysis (or gluconeogensis)
glyceraldehyde
product of the cleavage of fructose 1-P with enzyme aldolase B
- can be phosphorylated to glyceraldehyde 3-P (via triose kinase) and enter glycolysis
- can also be converted to glycerol to enter other pathways
Conversion of glucose to fructose via sorbitol
-enzyme: aldose reductase and sorbitol dehydrogeanse
aldose reductase
- conversion of glucose to fructose via sorbitol
- found in many tissues including lens, retina, schwann cells of peripheral nerves, liver, kidney, cells of ovaries and seminal vesicles
sorbitol dehydrogenase
- conversion of glucose to fructose via sorbitol
- ONLY found in the liver, ovaries, and seminal vesicles
Tissues that express only aldose reductase
will be damaged by long term elevation of blood glucose because it can make sorbitol but not further metabolize it.
excess glucose
converted to sorbitol
sorbitol accumulation
results in osmotic uptake of water, which can account for some of the symptoms seen in DM patients
- cataracts
- retinopathy
- nephropathy
- peripheral neuropathy
conversion of mannose to fructose 6-P
- mannose is C-2 epimers of glucose
- very little in the diet, most is synthesized intracellularly by fructose or recycled
- important component of glycoproteins
- substrate for hexokinase
- mannose is substrate for phosphomannoseisomerase
substrate for hexokinase
mannose. phosphorylated to mannose 6-P
substrate for phosphomannoseisomerase
mannose 6-P (hexokinase phosphorylated mannose to form this)
-converts mannose to fructose 6-P
essential fructosuria
- lack of fructokinase
- autosomal recessive (1:130,000)
- benign
- fructose accumulates in urine
Hereditary fructose intolerance (fructose poisoning
)
- autosomal recessive (1:20,000)
- absence of adores B, intracellular trapping fructose
- severe hypoglycemia, vomiting, jaundice, hemorrhage, hepatomegaly, renal dysfunction, hyperuricemia, and lacticacidemia
- fructose, sucrose, and sorbitol can cause hepatic failure and death
- therapy: rapid detection and removal and fructose and sucrose from diet
Why does fructose get trapped in cell in fructose poisoning?
absence of aldolase B, fructose is phosphorylated as in normal pathway, however builds up because can’t be further metabolized
production of fructose 1-P in someone with fructose poisoning
- ties up much of the available cellular phosphate, which means the liver and kidney cells are comprised
- leads to hepatomegaly, jaundice, hypoglycemia, and renal dysfunction
- large amount go AMP building up due to lack of ATP production results in AMP being degraded and resulting hyperuricemia
galactose metabolism
- isomer of glucose (C-4 epimer)
- dietary source-lactose from milk and milk products
- some from lysosomal degradation of complex carbs
- transport into cells is NOT insulin dependent
- metabolism is 2 steps to UDP galactose
step 1 of galactose metabolism
-phosphorylation of galactose with enzyme galactokinase
step 2 of galactose metabolism
formation of UDP galactose
- enzyme: galactose 1-phosphate uridyltransferase (GALT)
- transfer reaction
- UDP galactose can be converted to UDP-glucose and enter glucose metabolic pathways
galactokinase deficiency
- rare autosomal recessive
- elevation og galactose in blood and urine
- causes galactitol accumulation if galactose is present in the diet
- elevated galactitol can cause cataracts
- dietary restriction
aldose reductase in galactose metabolism
- physiologically unimportant in galactose metabolism unless galactose levels are too high
- elevated galatitol can cause cataracts
classic galactosemia
- GALT deficiency
- autosomal recessive
- galactosemia and galactosuria, vomitting, diarrhea, jaundice
- accumulation of galactose 1-P and galactitol in nerve, liver, lens, and kidney tissue causes liver damage, severe mental retardation, and cataracts
- prenatal Dx is possible by chorionic villus sampling
- rapid dx and removal of galactose from diet
synthesis of lactose
- milk sugar produced by lactating mammary glands
- synthesized in golgi
- enzyme: lactose synthase
lactose synthase
complex of 2 proteins
- A: B-D-galactosyltransferase found in a number of body tissues
- B: a-lactalbumin: its synthesis is stimulated by the peptide hormone prolactin
