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Questions and Answers
What is the primary cause of senile cataracts?
What is the primary cause of senile cataracts?
How do diabetic cataracts develop?
How do diabetic cataracts develop?
What distinguishes the retina from the lens in terms of energy production?
What distinguishes the retina from the lens in terms of energy production?
What is the most common treatment for cataracts?
What is the most common treatment for cataracts?
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Which of the following is NOT a known cause of cataracts?
Which of the following is NOT a known cause of cataracts?
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Which of the following is NOT a component of the eye's internal structure through which light passes?
Which of the following is NOT a component of the eye's internal structure through which light passes?
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The aqueous humor serves multiple purposes. Which of the following is NOT a function of the aqueous humor?
The aqueous humor serves multiple purposes. Which of the following is NOT a function of the aqueous humor?
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Which of the following is a key reason for the transparency of the cornea?
Which of the following is a key reason for the transparency of the cornea?
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What is the primary fuel source for the metabolism of the cornea?
What is the primary fuel source for the metabolism of the cornea?
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Why doesn't lactate accumulate significantly in the cornea despite glycolysis occurring?
Why doesn't lactate accumulate significantly in the cornea despite glycolysis occurring?
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The hexose monophosphate pathway plays a crucial role in the cornea. What is the main product of this pathway that is essential for corneal function?
The hexose monophosphate pathway plays a crucial role in the cornea. What is the main product of this pathway that is essential for corneal function?
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The protein VEGFR-3 plays a vital role in the cornea. What is its primary function?
The protein VEGFR-3 plays a vital role in the cornea. What is its primary function?
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What is the primary function of most lens proteins?
What is the primary function of most lens proteins?
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Which of the following molecules is NOT a major component of the lens?
Which of the following molecules is NOT a major component of the lens?
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What is the primary source of energy for lens metabolism?
What is the primary source of energy for lens metabolism?
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What is the significance of the lens's increase in size and thickness with age?
What is the significance of the lens's increase in size and thickness with age?
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Which of the following processes is responsible for maintaining the lens's redox-state balance?
Which of the following processes is responsible for maintaining the lens's redox-state balance?
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Which of these proteins is NOT a chaperone involved in maintaining lens protein structure?
Which of these proteins is NOT a chaperone involved in maintaining lens protein structure?
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Where are the lens cells responsible for growth located?
Where are the lens cells responsible for growth located?
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What is the name of the condition associated with a loss of near vision due to aging?
What is the name of the condition associated with a loss of near vision due to aging?
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What is the primary function of α-crystallin and β-crystallin in tissues other than the lens?
What is the primary function of α-crystallin and β-crystallin in tissues other than the lens?
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What is the estimated increase in thickness of the lens from birth to age 80?
What is the estimated increase in thickness of the lens from birth to age 80?
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When the cell has the need to produce nucleotides but already has a high level of NADPH, which of the following will occur?
When the cell has the need to produce nucleotides but already has a high level of NADPH, which of the following will occur?
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Which of the following is a true statement regarding the nonoxidative phase of the pentose phosphate pathway?
Which of the following is a true statement regarding the nonoxidative phase of the pentose phosphate pathway?
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In the oxidative portion of the pentose phosphate pathway, what is the fate of carbon 1 of glucose 6-P?
In the oxidative portion of the pentose phosphate pathway, what is the fate of carbon 1 of glucose 6-P?
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Which enzyme is responsible for the conversion of ribulose 5-P to ribose 5-P in the pentose phosphate pathway?
Which enzyme is responsible for the conversion of ribulose 5-P to ribose 5-P in the pentose phosphate pathway?
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What is the main function of the transketolase enzyme in the pentose phosphate pathway?
What is the main function of the transketolase enzyme in the pentose phosphate pathway?
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Which of the following is the product of the reaction catalyzed by transketolase in the pentose phosphate pathway?
Which of the following is the product of the reaction catalyzed by transketolase in the pentose phosphate pathway?
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What is the role of glutathione reductase in the cellular defense against active oxygen species?
What is the role of glutathione reductase in the cellular defense against active oxygen species?
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Which of the following is a harmful effect of active oxygen species on cells?
Which of the following is a harmful effect of active oxygen species on cells?
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How does reduced glutathione (GSH) protect cells from oxidative damage?
How does reduced glutathione (GSH) protect cells from oxidative damage?
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Which of the following molecules is directly reduced by glutathione reductase?
Which of the following molecules is directly reduced by glutathione reductase?
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What is the primary function of the enzyme transketolase in the pentose phosphate pathway?
What is the primary function of the enzyme transketolase in the pentose phosphate pathway?
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What is the primary consequence of a deficiency in glucose 6-phosphate dehydrogenase (G6PDH)?
What is the primary consequence of a deficiency in glucose 6-phosphate dehydrogenase (G6PDH)?
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Why is the pentose phosphate pathway linked to the supply of adequate amounts of glutathione?
Why is the pentose phosphate pathway linked to the supply of adequate amounts of glutathione?
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Why is the gamma linkage between the first two amino acids of glutathione important?
Why is the gamma linkage between the first two amino acids of glutathione important?
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Which of the following enzymes is responsible for inactivating active aldehydes in the cornea?
Which of the following enzymes is responsible for inactivating active aldehydes in the cornea?
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How does the pentose phosphate pathway and glutathione reductase protect the cornea?
How does the pentose phosphate pathway and glutathione reductase protect the cornea?
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Which of the following statements about the lens is TRUE?
Which of the following statements about the lens is TRUE?
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What is the function of the aldehyde carbon in the transketolase reaction?
What is the function of the aldehyde carbon in the transketolase reaction?
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What is the primary role of glutathione in the cell?
What is the primary role of glutathione in the cell?
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Study Notes
The Eye: Metabolism and Vision
- Light passes through the cornea, aqueous humor, lens, vitreous body, and focuses on the retina.
- Tears bathe the cornea's exterior; aqueous humor bathes the interior.
- Aqueous humor is isoosmotic, containing salts, albumin, globulins, glucose, and other components.
- It delivers nutrients to the cornea and lens, and removes metabolic waste.
- The vitreous humor is a gel that maintains the eye's shape and pliability.
Cornea Derives ATP from Aerobic Metabolism
- The eye, like the nervous system, primarily uses glucose for metabolism.
- The cornea, like the lens, diffracts light. Its clarity comes from the arrangement of collagen in the stroma.
- The cornea is permeable to water and oxygen.
- The cornea's water content is regulated by an ATP-driven water pump.
- The lack of blood vessels in the epithelial layer contributes to clarity.
- VEGFR-3, a protein in the anterior epithelial layer, prevents blood vessel growth.
- ATP is generated through aerobic glucose metabolism (glycolysis and the TCA cycle).
- Lactate doesn't significantly accumulate due to efficient metabolic pathways.
- 30% of glucose metabolism is via glycolysis, 65% via the hexose monophosphate pathway.
- The cornea has high hexose monophosphate pathway activity compared to other tissues.
- The cornea also has high glutathione reductase activity, which uses NADPH.
The Pentose Phosphate Pathway
- The nonoxidative reactions facilitate reversible conversion between intermediates of glycolysis and five-carbon sugars (e.g., ribose-5-P).
- Cell needs dictate the pathway's direction. If the cell needs ribose 5-P for nucleotides, it goes towards ribose 5-P. If it needs NADPH, it may convert ribose 5-P back to glucose 6-phosphate.
- NADPH is critical (made in the pentose phosphate pathway).
- Oxygen reactions can form harmful active oxygen species that damage lipids and proteins.
- Reduced glutathione (GSH) converts oxidized glutathione (GSSG) back to its reduced state; NADPH supports this process.
Glutathione
- Glutathione is a tripeptide (glutamate, cysteine, and glycine).
- It's found in the cell's millimolar range (1-10 mM).
- Reduced glutathione (GSH) maintains the cellular reduced state.
- Glutathione reductase utilizes NADPH to convert GSSG back to 2GSH.
Glucose 6-Phosphate Dehydrogenase Deficiency
- Deficiency impairs NADPH production.
- Inadequate NADPH leads to insufficient cellular glutathione reduction.
Glutathione Peroxidases
- Glutathione peroxidases are selenium enzymes that remove hydrogen peroxide (H₂O₂).
- These enzymes and the glutathione reductase cycle play a crucial role in protecting against free radical injury.
- NADPH is essential for the glutathione reductase cycle.
Cornea Active Oxygen and Lipids
- Pentose phosphate pathway and glutathione reductase protect the cornea by neutralizing active oxygen species.
- Peroxidized lipids may form active aldehydes.
- ALDH3A1, an aldehyde dehydrogenase isoform, inactivates active aldehydes.
Lens Function
- Lenses primarily consist of water and proteins (α-, β-, γ-crystallins).
- They obtain nutrients and eliminate waste through the aqueous humor.
- No blood vessels exist within the lens.
- They have specific protein requirements to maintain a clear, crystalline structural state.
- The lens is sensitive to osmolarity changes, oxidation-reduction imbalances, metabolite concentrations.
Lens Structural Integrity
- Maintaining osmotic balance is crucial; the Na+/K+ ATPase helps with salt concentration.
- The glutathione reductase cycle safeguards against redox state imbalances.
- Protein synthesis and other metabolic processes sustain growth and integrity in the lens periphery.
- α- and β-Crystallins (small heat shock proteins) maintain lens protein structure in their native state.
- Mutations in crystallins can lead to cataract formation and potential muscular issues.
Lens Metabolism
- About 85% of glucose metabolism in the lens occurs through glycolysis, with 3% utilizing the TCA cycle, and the remaining using the pentose phosphate pathway.
- The lens nucleus remains from birth, growing in size and thickness with age.
- This growth pattern affects the lens's elasticity which results in presbyopia (loss of near vision).
- A threefold increase in lens size and a 12-fold increase in thickness from birth to 80 years are observed.
Cataract
- Cataracts are lens opacities stemming from varied conditions.
- The two most common are senile and diabetic cataracts.
- Senile cataracts correlate to age-related changes in lens crystallins and protein molecules (e.g., breakdown at C-terminal ends, deamidation, and racemization).
Diabetic Cataracts
- Increased aldose reductase activity, alongside polyol dehydrogenase activity, leads to osmotic imbalances in the lens.
- Elevated glucose levels increase sorbitol accumulation; it cannot be effectively metabolized by the lens.
- This accumulation leads to structural changes and impairment within the lens proteins, and increase in the rate of protein aggregation and denaturation
- The higher glucose concentration in diabetic individuals leads to more visible light scatter, characteristic of cataract formation.
Retinal Metabolism
- The retina heavily relies on anaerobic glycolysis for ATP.
- Unlike the lens, the retina is vascularized.
- The fovea centralis, the central region of the macula (a region in the retina), is rich in cones. This is the area of greatest visual activity.
- Mitochondria are present in connecting retinal rods and cones, but not in the outer segments containing visual pigments.
Glucose Conversion to Fructose via Sorbitol
- Most sugars are phosphorylated upon entering cells, trapping them within the cells; this prevents them from freely entering the cytoplasm
- Sugar alcohols, like sorbitol, are formed via the reduction of an aldehyde group in a monosaccharide, producing an extra hydroxyl group.
Sorbitol Synthesis
- Aldose reductase synthesizes sorbitol. Its activity is high in the retina, lens, kidneys, and peripheral nerves.
- Sorbitol dehydrogenase converts sorbitol to fructose (primarily in the liver, ovaries, and seminal vesicles).
- This pathway helps fructose become available to cells for glycolytic metabolism.
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Description
Explore the intricate details of how the eye functions, focusing on metabolism and vision. This quiz covers the roles of various components like the cornea, aqueous humor, and vitreous humor in maintaining eye health and clarity. Dive into the biochemical processes that support these structures.