Metabolism of Monosaccharides and Disaccharides; PPP Flashcards
Entry points of sugars into glycolysis
(Chart/Big Picture/General Idea)
Sucrose is a disaccharide of ____ and ____
Sucrose is a disaccharide of fructose and glucose
Fructose can be found in the following sources (5 examples)
Frucoste can be found in the following sources:
- Table sugar
- Sugar cane
- Fruits/Fruit sugar
- Honey (50% fructose)
- High fructose corn syrup (55% fructose and 45% glucose)
Note: Sucrose is a disaccharide made from fructose and glucose
____ (in all tissues) converts fructose to fructose-6-phosphate; this enzyme has a high Km (low affinity) for fructose
____ (found in liver, kidney, and small intestine) converts fructose to fructose-1-phosphate and has a very low Km (high affinity), high Vmax, and rapidly phosphorylates fructose
Hexokinase (in all tissues) converts fructose to fructose-6-phosphate; this enzyme has a high Km (low affinity) for fructose
Fructokinase (found in liver, kidney, and small intestine) converts fructose to fructose-1-phosphate and has a very low Km (high affinity), high Vmax, and rapidly phosphorylates fructose
Why is fructose metabolism to trioses more rapid than glucose metabolism?
Because it bypasses the rate limiting step of glycolysis which is PFK-1 (phosphofructokinase-1)
The metabolism of fructose occurs principally in the ____
Fructose-1-phosphate is cleaved into ____ and ____ by ____
The metabolism of fructose occurs principally in the ____
Fructose-1-phosphate is cleaved into ____ and ____ by ____
There are ____ aldolase isoforms which are __, __, and __; all are able to cleave ____
There are three aldolase isoforms which are A, B, and C; all are able to cleave fructose-1,6-bisphosphate
Aldolase A is present present in ____ and most other tissues; it can cleave ____ but it cannot leave ____
Aldolase A is present present in muscle and most other tissues; it can cleave fructose-1,6-bisphosphate but it cannot leave Fructose-1-Phosphate
Alsolase B is only prsesent in the ____, kidney, and small intestines; it can cleave ____ and ____
Alsolase B is only prsesent in the liver, kidney, and small intestines; it can cleave fructose-1-phosphate and fructose-1,6-bisphosphate
Aldolase C is ubiquitously expressed in most tissues, though it is predominantly expressed in the ____; can cleave ____ but cannot cleave ____
Aldolase C is ubiquitously expressed in most tissues, though it is predominantly expressed in the brain; can cleave fructose-1,6-bisphosphate but cannot cleave fructose-1-phosphate
Aldolase A, B, and C can all cleave fructose 1,6-bisphosphate; which aldolases cannot cleeave F-1-P?
Aldolase A and Aldolase C cannot cleave F-1-P
Glyceraldehyde 3-phosphate can be used as glycolytic intermediates but can also be used for ____ to produce glucose
Glyceraldehyde 3-phosphate can be used as glycolytic intermediates but can also be used for gluconeogenesis to produce glucose
In liver, aldolase __ is highly expressed whereas aldolase __ and __ expression is much lower. Therefor aldolase __ is critical for fructose metabolism as well as gluconeogenesis
In liver, aldolase B is highly expressed whereas aldolase A and C expression is much lower. Therefor aldolase B is critical for fructose metabolism as well as gluconeogenesis
Essential Fructoseria
Lack of ____
Autosomal ____
Benign condition that results in ____ in the urine
Essential Fructoseria
Lack of fructokinase
Autosomal recssive
Benign condition that results in fructose in the urine
Hereditary Fructose Intolerance (“Fructose Poisoning”)
Absence of ____ leads to intracellular trapping of ____
Autosomal ____
Fructose/sucrose/sorbitol can cause ________ (may see elevated ____) and death
Also causes (8 examples):
Therapy: rapid detection and removal of ____ and ____ from the diet
Hereditary Fructose Intolerance (“Fructose Poisoning”)
Absence of aldolase B leads to intracellular trapping of fructose 1-phosphate
Autosomal ressive
Fructose/sucrose/sorbitol can cause hepatic failure (may see elevated ALT/AST) and death
Also causes (8 examples):
- Severe hypoglycemia
- Vomiting
- Jaundice
- Hepatomegaly
- Hemorrhage
- Renal dysfunctions
- Hyperuricemia
- Lacticacidemia
Therapy: rapid detection and removal of fructose and sucrose from the diet
Hereditary Fructose Intolerance (“Fructose Poisoning”)
First appears when baby is weaned from milk and is fed food containing ____ or ____
____ accumulates, resulting in the a drop of the inorganic phosphate (Pi) levels, therfore a drop in ____ production. This drop in Pi also inhibits ____.
As ____ falls, AMP rises and is degraded, causing hyperuricemia and lactic acidemia
Decrease of available ____ also decreases ____ (causing hypoglycemia with vomiting) and decreases ________ (causing a decrease in blood clotting factors and other essential proteins)
Hereditary Fructose Intolerance (“Fructose Poisoning”)
First appears when baby is weaned from milk and is fed food containing sucrose or fructose
Fructose 1-phosphate accumulates, resulting in the a drop of the inorganic phosphate (Pi) levels, therfore a drop in APT production. This drop in Pi also inhibits glycogenolysis.
As ATP falls, AMP rises and is degraded, causing hyperuricemia and lactic acidemia
Decrease of available ATP also decreases gluconeogenesis (causing hypoglycemia with vomiting) and decreases protein synthesis (causing a decrease in blood clotting factors and other essential proteins)
Sources of galactose
- Dairy products
- Blackeyed peas
- Sugar beets
- Some beans
____ is a disaccharide of galactose and glucose
Capacity to metabolize galactose in infants is higher than adults
Galactose
Lactose is a disaccharide of galactose and glucose
Capacity to metabolize galactose in infants is higher than adults
Galactose
Galactokinase Deficiency
Rare autossomal ____ disorder
Causes elevation of ____ in blood (called ____) and urine (called ____)
Causes ____ accumulation if ____ is present in the diet
Elevated ____ can cause cateracts
Treatment is dietary restriction
Galactokinase Deficiency
Rare autossomal ressive disorder
Causes elevation of galactose in blood (called galactosemia) and urine (called galactosuria)
Causes galactitol accumulation if galactose is present in the diet
Elevated galactitol can cause cateracts
Treatment is dietary restriction
Classic Galactosemia
________ deficiency
Autosomal ____
Causes ____, ____, ____, ____, and ____
Accumulation of ____ and ____ in nerve/lens/liver/kidney tissue causes liver damage, severe mental retardation, and ____
Prenatal diagnosis is possible by chorionic villus sampling; newborn screen also available
Therapy: Rapid diagnosis and removal of ____ (and therefore ____) from diet
Despite adequate treatment, at risk for developmental delays, and in fameles, premature ovarian failure
Classic Galactosemia
Galactose 1-phosphate uridyltransferase (GALT) deficiency
Autosomal recessive
Causes galactosemia, galactosuria, vomiting, diarrhea, and jaundice
Accumulation of galactose 1-phosphate and galactitol in nerve/lens/liver/kidney tissue causes liver damage, severe mental retardation, and cataracts
Prenatal diagnosis is possible by chorionic villus sampling; newborn screen also available
Therapy: Rapid diagnosis and removal of galactose (and therefore lactose) from diet
Despite adequate treatment, at risk for developmental delays, and in fameles, premature ovarian failure
________ converts galactose (when accumulated due to a deficiency) into galactitol
Elevated galactitol levels can cause ____
Aldose Reductase converts galactose (when accumulated due to a deficiency) into galactitol
Elevated galactitol levels can cause cataracts
The Polyol Pathway for synthesis of fructose from glucose can lead to pathological ____ accumulation
The Polyol Pathway for synthesis of fructose from glucose can lead to pathological sorbitol accumulation
Aldoase Reductase converts:
Aldoses to ____
Galactose to ____
Glucose to ____
Aldoase Reductase converts:
Aldoses to alcohols
Galactose to galactitol
Glucose to sorbitol
Sorbitol dehydrogenase converts ____ to ____
Sorbitol dehydrogenase converts sorbitol to fructose
Sorbitol dehydrogenase is low or absent in ____, ____, kidney, and nerve cells, which exacerbates sorbitol accumulation
In hyperglycemia/hypergalactosemia (and adequate NADPH), ____ and ____ accumulate in the ________, kidney, and nerve cells, causing increased osmotic pressure
Some of the pathologic alterations asssociated with diabetes, including ____ formation, peripheral neuropahty, and microvascular problems leading to nephropathy and retinapthy, can be attributed, in part, to this
Sorbitol dehydrogenase is low or absent in retina, lens, kidney, and nerve cells, which exacerbates sorbitol accumulation
In hyperglycemia/hypergalactosemia (and adequate NADPH), sorbitol and galactitol accumulate in the lens of the eye, kidney, and nerve cells, causing increased osmotic pressure
Some of the pathologic alterations asssociated with diabetes, including cataract formation, peripheral neuropahty, and microvascular problems leading to nephropathy and retinapthy, can be attributed, in part, to this
What are the two phases of the Pentose Phosphate Pathway and what do they do?
- The Oxidative Phase: Generates NADPH required for biosynthetic pathways and ROS detoxification
- The Nonoxidative Phase: Interconverts monosaccharides to produce ribose-5P for nucleotide synthesis, and also regnerates glucose-6P to maintain NADPH production by the oxidative phase
What are the key enzymes in the Pentose Phosphate Pathway and why are they important?
Glucose-6P dehydrogenase: Committed Step; occurs in oxidative phase; is feedback inhibited by NADPH
Transketolase and Transaldolase: These two enzymes catalyze reversible “carbon shuffle” reaction of the nonoxidative phase
Glutathione Defence System
Glutathione (GSH) is necessary for the removal of ____ and ________ generated by ROS
Upon neutralizing ____ and ____, two glutathione (GSH) are oxidized together producing ____
____ is used for the reduction of oxidized ____ to reduce to glutathione (GSH)
Glutathione Defence System
Glutathione (GSH) is necessary for the removal of H2O2 and lipid peroxides generated by ROS
Upon neutralizing H2O2 and peroxides, two glutathione (GSH) are oxidized together producing GSSG
NADPH is used for the reduction of oxidized GSSG to reduce to glutathione (GSH)
In RBCs, generation of superoxide ion from nonenzymatic oxidation of Hgb provides source of ROS
The glutathione defense system if compramised by ________ deficiency, infections, certain drugs, and purine glycosides of fava beans
As a consequence ________ (aggregates of cross-linked Hgb) form on the cell membranes. Causes mechanical stress, which along with ROS on the cell membrane causes ____
In RBCs, generation of superoxide ion from nonenzymatic oxidation of Hgb provides source of ROS
The glutathione defense system if compramised by glucose-6-phosphate ddehydrogenase deficiency, infections, certain drugs, and purine glycosides of fava beans
As a consequence Heinz bodies (aggregates of cross-linked Hgb) form on the cell membranes. Causes mechanical stress, which along with ROS on the cell membrane causes hemolysis (hemolytic anemia)
Uses of NADPH (general idea)
Uses of NADPH:
- Phagocytosis by WBCs
- Synthesis of NO (nitric oxide)
- Cytochrome P450 monooxygenase system
- Protection against oxidative stress by Glutathione preoxidase
- Reductive biosynthesis (e.g. Fatty acid synthesis, sterols, steroids)
- Maintenance of reduced glutathione
- Reduction of hydrogen peroxide
