Fructose and Galactose Flashcards
1
Q
Glucose (2)
A
- at the center of carbohydrate metabolism
- major dietary sugar
2
Q
Fructose (3)
A
- ingested as monosaccharide or as part of sucrose
- enter cells by facilitate diffusion on the GLUT% transporter
- it is metabolized to intermediates of glycolysis
3
Q
Fructose metabolism (3) -what happen, steps
A
- Fructokinase phosphorylates fructose, forming fructose-1-phosphate
- Fructose-1-phosphate is cleaved by aldolase B to dihydroxyacetone phosphate and glyceraldehyde
- Glyceraldehyde is then phosphorylated to glyceraldehyde-3-phosphate by triose kinase
ATP is necessary in step 1 and 3
4
Q
Fructose metabolism
-characteristics (3)
A
- Dihydroxyacetone-P and glyceraldehyde 3-phosphate are intermediates of the glycolytic pathway
- Occurs in the liver and less in the small intestinal mucosa and proximal epithelium of the renal tubule
- aldolase B is the rate-limiting enzyme
5
Q
Defects in Fructose Metabolism (2)
A
- Lack of hepatic fructokinase –> essential fructosuria (benign and asymptomatic)
- Absence of aldolase B –> leads to hereditary fructose intolerance –> patients accumulate high amounts of fructose- 1- phosphate in their livers, which inhibits liver glycogen phosphorylate causing fructose induce hypoglycemia.
6
Q
Consequences of High Fructose Intake (2)
A
- in the liver, fructose increases fatty acid and triacylglycerol synthesis and VLDL secretion and LDL cholesterol
- acute loading of the liver with fructose traps inorganic phosphate in fructose-1-phosphate and diminishes ATP synthesis
7
Q
Galactose Metabolism
-characteristics (2)
A
- ingested primary as lactose, which is converted to galactose and glucose in the intestine
- converted to glucose in the liver
8
Q
Galactose Metabolism (3) -steps, what happen
A
- Galactokinase catalyzes the phosphorylation of galactose using ATP
- Galactose-1-phosphate and UDP-glucose are converted to UDP-galactose and glucose-1-phosphate by galactose-1-P-uridyltransferase
- UDP-galactose is converted to UDP-glucose by UDP-glucose epimerase. It is reversible
9
Q
Galactosemia (4)
A
- Galactose-1-phosphate uridyl-transferase (GALT) deficiency
- autosomal recessive disorder
- prevents the person from processing galactose
- accumulation of galactose-1-phosphate in nerve, lens, liver and kidney causes liver damage, severe mental retardation and cataracts
10
Q
Regulation of carbohydrates metabolism
-mechanisms that are responsible for regulating the activity of enzymes (3)
A
1- changes in the rate of enzyme synthesis
2- covalent modification of reversible phosphorylation
3- allosteric effects
11
Q
Major pathways of glucose utilization (4)
A
- Storage –> glycogen, starch, sucrose
- Oxidation via glycolysis –> pyruvate
- Oxidation via pentose- phosphate pathway –> ribose-5-phosphate
- Synthesis of structural polymers –> extracellular matrix and cell wall polysaccharides
12
Q
Pentose phosphate pathway (4)
-characteristics
A
- an alternative metabolic pathway for glucose oxidation in which NO ATP is generated
- principal product: ribose-5-phosphate
- occurs in the cytoplasm
- two phases: oxidative and non-oxidative phase
13
Q
3 intermediates of pentose phosphate pathway which are useful in other pathways
A
- Ribose-5-phosphate
- Fructose-6-phosphate
- Glyceraldehyde-3-phosphate
14
Q
Pentose phosphate pathway: oxidative phase
A
-3 reaction which forms: ribulose-5-phosphate, CO2, 2 NADPH for each molecule of glucose-6-phosphate oxidized
Glucose-6-phosphate + 2 NADP+ + H20 –> ribulose-5-phosphate + 2 NADPH + 2H+ + CO2
15
Q
Pentose phosphate pathway: non-oxidative phase (3)
A
- occurs in all cell types synthesizing nucleotides and nucleic acids
- reversible
- permits ribulose-5-phosphate to be converted to ribose-5-phosphate, fructose-6-phosphate and glyceraldehyde-3-phosphate
16
Q
Regulation of pentose phosphate pathway (3)
A
- Key regulatory enzyme: glucose-6-phosphate dehydrogenase
- NADPH –> inhibitor
- activity is stimulated by oxidized form of glutathione
17
Q
Complex carbohydrates
- classification of complex carbohydrates
- characteristics of each
A
-Glycoprotein or Proteoglycans
GP –> hetero-oligosaccharide which is covalently attached to a protein
PG –> proteins and glycosaminoglycan (hetero-polysaccharide) chains
18
Q
Glycoproteins (4)
A
- short glycan chains –> 20 sugars
- highly branched and do not have a repeating unit
- usually contain –> amino sugars (N-acetlyglucosamine or N-acetyl-galactosamine), neural sugars (D-galactose and mannose, I- fucose), acidic sugar silic acid (N-acetylneuraminic acid)
- usually found –> outer face of the plasma membrane, extracellular matrix and blood
19
Q
Glycosaminoglycans (GAG) (2)
A
- unbranched acidic polysaccharides that consist of repeating disaccharide units
- composed of an amino sugar and uronic acid
20
Q
Pentose phosphate pathway: oxidative phase
-particularly important in: (3)
A
- liver, lactating mammary glands and adipose, which are active in NADPH dependent biosynthesis of fatty acids
- testes, ovaries and placenta which are active in the NADPH dependent biosynthesis of steroid hormones
- erythrocytes, which require NADPH to keep glutathione reduced
21
Q
Examples of common Glycosaminoglycans (5)
A
- Hyaluronic acid
- Chondroitin sulfate
- Keratan sulfate
- Dermatan sulfate
- Heparin
22
Q
Hyaluronic acid (6)
A
- largest (n=5,000 - 30,000)
- negative charges bind lots of water and cations
- Glucuronic acid + N-acetylglucosamine
- β(1–>3): inside / β(1–>4): between disaccharides
- abundant in vitreous humor of eye and synovial fluid of joints
- viscous solutions (low concentrations) and hydrated gel (high concentrations)
23
Q
Sulfated glycosaminoglycans (4)
A
- GAG’s that carry sulfate group in the form of sulfate esters
- sulfate groups contribute additional negative charges
- much shorter
- covalently bound to amino acid side chains in a core protein
24
Q
Chondroitin Sulfate (3)
A
- component of cartilage, tendons, ligament and aorta
- Glucuronic acid + N-acetlygalactosamine
- β(1–>3): inside / β(1–>4): between disaccharides
25
Keratan Sulfate (3)
- found in cornea, cartilage and intervertebral disks
- Galactose + N-Acetylglucosamine
- β(1-->4): inside / β(1-->3): between disaccharides
26
Dermatan sulfate (3)
- contributes to the flexibility of the skin, present in blood vessels and heart valves
- Iduronic Acid + N-Acetylgalactosamine
- β(1-->3): inside / β(1-->4): between disaccharides
27
Heparin (4)
- formed by mast cells and basophils
- anticoagulant and lipid- cleating properties
- Glucuronic acid + Glucosamine
- α(1-->4): inside / α(1-->4): between disaccharides
28
Proteoglycan (4)
- core protein with its covalently attached GAGs
- major components of the amorphous ground substance of CT
- are responsible for the slimy consistency of mucus secretions
- contain: heparan sulfate and chondroitin sulfate (less common)
29
Large proteoglycan aggregates
Composed mostly of collagen (type I and II) and aggrecan
30
Aggrecan (5)
- Core protein of 2316 amino acids
- Two globular domains at the amino end
- Keratan sulfate and chondroitin sulface (more of them) domain
- Globular domain at the carboxyl end
- Hyaluronic acid molecules binds up a few hundred aggrecan molecules
31
Aggrecan molecule
- function
- how does it work (4)
-act as a lubricant, absorbs and dissipates impact forces
- GAG's have negatively charged group, which means they will be attracted to H20 molecules.
- when aggrecan molecules are in their initial position --> a lot of H20 molecules will be absorbed and attached to them
- when an impact is applied, H20 molecules leave , slightly deforming the molecule
- as soon as force is released, H20 molecules will rush back
32
Synthesis of proteoglycans (3)
- they are processed through the secretory pathway
- core protein is made by ribosomes on the rough ER
- polysaccharides are constructed in the ET and golgi apparatus
33
Degradation of proteoglycans (2)
- extracellular proteoglycans are endocytosed and sent to the lysosomes
- polysaccharide chains of the GAGs are degraded by the stepwise removal of monosaccharides from the nonreducing end
34
Mucopolysaccharides (4)
- deficiency of only one of the required lysosomal enzymes can interrupt the ordered sequence of GAg degradation
- undegraded GAGs accumulate in the lysosomes
- partially degraded polysaccharide appears in blood and urine
- Lysosomal storage disease --> mucopolysaccharidosis
35
Mucopolysaccharidosis (3)
- enzyme deficiency is generalized, affecting all organ systems
- inheritance is autosomal recessive or X-linked recessive
- symptoms develop gradually
36
Problems caused by the buildup of GAGs in the tissues (3)
- Defects in the degradation of keratan sulfate and dermatan sulfate --> CT abnormalities
- hearing loss, short stature
- valvular heart disease
37
Accumulation of Heparan sulfate
| -consequences
-mental retardation and neurological degradation
IT IS THE ONLY IMP GAG IN THE CNS
38
GAG's that do not accumulate
-chondroitin sulfate and hyaluronic acid
they can be degraded by lysosomal hyaluronidase and endoglycosidase
39
Treatment of mucopolysaccharidoses (3)
- Replacement of the missing enzyme
- after injected into the bloodstream, the enzyme is endocytosed and targeted to the lysosomes
- limitations: high cost, formation of antibodies to the enzyme, inability of the enzymes to enter the brain
