Flashcards in Hexose Metabolism Deck (47):
How does fructose enter the cell?
Glut 5 transporter
1. What deficiently leads to fructokinase deficiency?
2. What is the result?
1. Fructose is unable to be converted to fructose 1-phosphate
2. Fructose is excreted in the urine
What are some of the results of Hereditary fructose intolerance?
1. Hereditary deficency of hepatic fructose 1- Phosphate aldolase B
2. Build up of F-1-P in the liver and kidney
3. Inhibition of gluconeogenesis and glycogenolysis
4. Depletion of ATP
What is the net reaction for galactose metabolism?
Galactose + ATP ----> Glucose 1-P + ADP
What enzyme phosphorylates Galactose?
What is the second most common sugar in our diet?
What transporter does fructose enter on? Where is this located (recall from earlier lecture)
GLUTV, small intestine
Describe, briefly, how fructose enters glycolysis.
FructoseF1P via frucokinase aldolase B produces G3P and DHAP which enters via triose phosphate isomerase
What is the major fuel source for sperm?
Fructose (sertoli cells)
What is the presentation of fructosuria?
Pretty benign, fructose appears in urine
What is the presentation for hereditary fructose intolerance?
Toxic deficiency of aldolase B, f1P is toxic in the liver, vomiting, hypoglycemia, etc. uses up ATP stores and inhibits gluconeogenesis and glycogenolysis
How does galactose enter glycolysis?
Galactosegalactose 1 phosphate via galactokinase glucose 1 phosphate via galactose 1 phosphate uridilyl transferase (Leloir pathway) via UDP glucose/galactose exchange
What causes classical galactosemia? Nonclassical?
Deficiency of galactose-1-phosphate uridyl transferase; defeiciency of galactokinase
What is the presentation of classical galactosemia?
Accumulation of Galactose1P, vomiting, hypoglycemia, lots of other symptoms, galactose in blood and tissues
What is the presentation of nonclassical galactosemia?
Galactose in blood and tissues, galactitol accumulates in lens which can lead to cataracts, must avoid galactose in diet completely
What is the purpose of the pentose phosphate pathway?
Produce reducing equivalents, ribose phosphates for nucleotide biosynthesis,
How many NADPH are made per glucose6phosphate oxidized?
What stage produces NADPH? Ribose 5 phosphate?
Oxidative, non oxidative stages respectively
What is the predominant form of aldolase in liver? Muscle?
B, A, respectively: B is used for glycolytic reasons, A is used for gluconeogenic reasons
T or F: aldolase B has a higher affinity for Fructose 1 phosphate than it does for G3P and DHAP.
What is the rate limiting step for fructose metabolism?
Aldolase B cleavage to G3P and DHAP
What pathway synthesizes fructose?
Describe the pathway of fructose synthesis
Glucosesoribitol/polyol via aldolase reductasefructose via sorbitol DH
Describe the oxidative step for the PPP.
Glucose 6 phosphateto 6 phosphoglucono-delta-lactone with generation of NADPH via glucose 6 DH (NADPH inhibits this step)6 phosphogluconolactone to 6 phosphogluconate via glucolactonase reduced to ribulose 5 phosphate via 6 phosphoglucnate DH (therefore generate 2 NADPH and 1 mol ribulose 5 phosphate)
Describe non-oxidative step.
Transketolase takes 2 C fragment from xyulose 5 phosphate (which epiremized from ribose 5 phosphat) and puts it on another ribose 5 phosphate which forms sedoheptulose 7 phosphate and G3P, Sedoheptulose 7P and G3P then form erythrose 4 phosphate and F6P via a transaldolase, eryhthrose 4P then gains another2C fragment from another xyulose 5 phosphate to form F6P and G3P (basically forming 3 glycolytic intermediates)
What happens in glucose 6 phosphate dehydrogenase deficiency?
Less NADPHOxidative damage, loss of reducing power to eliminate radicalsprecipitation of Hb in RBC’s cause Heinz bodies and hemolytic anemia
Where is fructose mainly metabolized and what is it converted to?
metabolized in the liver and converted to pyruvate under fasting conditions
Describe the 2 steps of fructose metabolism
1. Fructose phosphorylated by fructose-1-phosphate
2. fructose 1-phosphate cleaved by aldolase B to form DHAP and glyceraldehyde => glyceraldehyde 3-phosphate
Which intermediate from fructose metabolism will produce pyruvate leading to the TCA cycle
How is fructose produced from glucose?
1. glucose reduced to sorbitol by aldose reductase
2. Sorbitol reoxidized to form fructose
Where would you find fructose derived from glucose? What is the function of fructose in this location?
seminal vesicles and is the major energy source for sperm
Describe essential fructosuria and explain the result of the disorder
inherited with accumulation of fructose
fructose is excreted in urine where some may be phosphorylated by HK for glycolysis
Describe hereditary fructose intolerance and explain the results of the disorder
hereditary deficiency of hepatic fru-1-P aldolase B leading to an accumulation in liver and kidney
-will inhibit gluconeogenesis and glycogenolysis
Describe galactose metabolism and energy req.
Galactose + ATP => Galactose 1-P + UDP-glucose => Glucose-1-P + ADP => G-6-P (liver) for glucose in blood
Describe classical galactosemia
-deficiency of galactose-1-phosphate uridyl transferase
-accumulation of gal-1-P in tissues and will result in hypoglycemia
Describe nonclassical galactosemia
-Deficiency of galactokinase which converts gal => gal-1-P
-results in galactose accumulation in blood and tissue with cataract formation
Describe the irreversible oxidative reactions of the pentose phosphate pathway
-1 carbon of G-6-P is released as CO2;
-NADPH is generated;
-ribulose 5-phosphate is produced
Why are NADPH, ribose 5-phosphate, and pentose sugars formed?
-NADPH: required for reducing equivalents
-Ribose 5-phosphate: nucleotide biosynthesis
- pentose sugars: rearrange for glycolytic/gluconeogenic intermediates
Where does the pentose phosphate pathway occur?
most tissues especially ones that use lots of NADPH
Describe the first 2 stages of the pentose phosphate pathway
1st=>oxidative and generates 2 mol of NADPH per -G-6-P oxidized
2nd=>non-oxidative and generates ribose 5-P that is converted unused to intermediates to glycolytic pathway
T/F NADPH is a strong inhibitor to G-6-P dehydrogenase
The NADPH generation will provide what other reactions to occur?
fatty acid synthesis, glutathione reduction (protection against oxidative damage)
T/F The cell dictates the direction of the pathway
Wrt NADPH only, how is the direction of the pathway dictated?
oxidative rxns produce;
nonoxidative rxns convert ribose-5-P to G-6-P to produce more NADPH
Wrt to ribose 5-P, how is the direction of the pathway dictated?
only nonoxidative rxns as NADPH inhibits G-6-P dehydrogenase so fruc-6-P and glyceraldehyde 3-P and ribose 5-P are produced
Wrt to NADPH and pyruvate, how is the direction of the pentose phosphate dictated?
oxidative and nonoxidative rxns are used
Nonoxidative=>convert to intermediates to pyruvate via glycolysis