Biochem of the Eye Quiz 5- ocular gags, lipid storage disorders, eicosanoids, graves' disease, steroids, and other hormones

The connective, extracellular tissue that we find in the eye has two sides:

1) collagen side

2) glycosaminoglycan side

the collagen side and glycosaminoglycan side work together to form _________________.

tissues

Glycosaminoglycans (GAGs) were formerly called ______________________________.

mucopolysaccharides

what are GAGs

polymers that consist of repeating two sugar units of a sugar and an amino sugar.

Chondroitin sulfate has an N-acetylated group in the ____________-hand sugar

right

Chondroitin sulfate has ___________________ charges on the carboxylate and sulfate groups

negative

Chondroitin sulfate has alternating....

beta 1--->3 and beta 1 ---->4 linkages

In chondroitin sulfate, what is the carboxylate in the upper position?

uronate

In chondroitin sulfate, what is the carboxylate in the inferior position?

iduronate

In chondroitin sulfate, ________________ may take place in several positions.

sulfation

Each time sulfation takes place on chondroitin sulfate, a ___________________ charge is added.

negative

What are the 4 basic GAG units that occur in the eye?

1) hyaluronic acid

2) chondroitin sulfate

3) keratan sulfate

4) dermatan sulfate

HA is a component of the ____________________.

vitreous

HA has one less ________________ per unit.

charge

HA contains ____________________ rather than N-acetyl galactose.

N-acetyl glucose

Keratan sulfate is a component of the ________________________.

cornea

Chondroitin sulfate is a component of the ______________________.

cornea

Keratan sulfate has ____________________ in the left hand unit.

galactose

Keratan sulfate has _________________ in the right hand unit.

N-glucosamine

Dermatan sulfate is a component of the ___________________________.

cornea

Dermatan sulfate contains ____________________________________.

iduronic acid

What makes the biggest difference among corneal components?

the accumulation of negative charges

corneal GAGs have relatively ____________ lengths.

short

hyaluronate is composed of _________________ glycan units per molecule, therefore it can be contained in a much larger volume

~50,000

hyaluronate in a very twisted and curved form, can absorb tremendous volumes of _______________________.

water

the water absorbing nature of hyaluronate also helps the gel to have ________________________ properties.

viscoelastic

viscoelastic property

allows deformation with the ability to return to an original shape with the same volume

glycoprotein

a protein to which sugars (oligosaccharides) are bound

proteoglycan

a protein that has GAGs bound to it

for this class, proteoglycans will refer to holoproteins which are...

less protein than GAGs

rhodopsin is a __________________.

glycoprotein

lumican is a ____________________.

proteoglycan

what are the 2 proteoglycans found in the human corneal stroma?

- decorin

- lumican

each protein can bind to __________ GAGs

1-3

even more confusing...

decorin and lumican are also technically _________________________.

glycoproteins

lumican binds only with _________________________.

keratan sulfate

______________ may bind to either chondroitin sulfate, dermatan sulfate, or keratan sulfate

decorin

lumican and decorin act as molecular ________________________ between type 1 collagen fibers.

spacers

decorin and lumican exhibit some ______________________.

viscoelasticity

what happens to damaged GAGs?

transported to lysosomes and enzymes degrade them into simpler molecules that can be reused.

mucopolysaccharidoses

disease resulting in defect of degrative enzymes involved in breaking down GAGs

how does mucopolysaccaridoes pathology arise?

partially degraded GAGs accumulate in the lysosomes, engorge the cells and then spill out into nearby tissues

what are mucopolysaccaridoes also known as?

metabolic storage diseases

besides GAGs, mucopolysaccaridoes can also involve ______________________________.

lipids and polysaccharides

What causes Hurler syndrome?

a-iduronidase deficiency

when is the onset of Hurler syndrome?

infancy

When is there linear arrest in growth of Hurler syndrome?

~ 1 year of age

how does Hurler syndrome clinically present?

psychomotor retardation, distorted facial appearance, deformed/stiff joints, enlarged liver and spleen

in a patient with Hurler syndrome, _____________ piles up in the joints and internal organs.

GAGs

what happens to the eyes of a patient with Hurler syndrome?

the cornea becomes cloudy and the optic nerve degenerates; glaucoma may occur

Hurler syndrome causes an accumulation of ___________________________________ in the tissues including the eyes, blood and urine.

dermatan sulfate and heparan sulfate (2:1)

Hurler syndrome is usually fatal within a few years, due to _______________________________.

congestive heart failure and respiratory pulmonary infections.

Each lysosomal storage disease is ______________________ caused and comparatively rare.

genetically

In the degradation of the GAG dermatan sulfate...

the early involvement of a-L-iduronidase in the degradative sequence, leaving the molecule in a large, nearly intact form to pile up in tissues and fluids.

how is hurler syndrome assayed?

An artificial substrate replaces dermatan sulfate (or other GAG) with a fluorogen bound to iduronic acid.

then when an enzyme lyses the substate, the product fluoresces in proportion to the activity of the enzyme

possible treatments for hurler syndrome

1) bone marrow/umbilical chord blood transplantation

2) enzyme replacement therapy

3) gene replacement therapy

Tay-Sach's Disease is caused by a _______________________ deficiency

hexosaminidase

with Tay-Sach's disease, brain cells start dying by about _______ months.

6

survival for patients with Tay-Sach's disease is usually not beyond ______ years.

5

is there a cure or treatment for Tay Sach's Disease

no

What enzyme is deficient in Tay-Sach's disease?

hexosaminodase

Tay-Sach's Disease is a __________________________ in which GM2 accumulates in neural tissue and destroys neural cells in both the brain and neural retina.

sphingolipidosis

Inclusion-cell disease is a __________________________.

mucolipodosis

What disease does inclusion cell disease resemble?

Hurler's disease

Inclusion-cell disease occurs due to a defect in a packaging enzyme that prepares ___________________ for transport to its lysosome.

B-galactosidase

What packaging enzyme is defective in Inclusion cell disease?

N-acetylglucosamine 1-phosphotransferase

What does N-acetylglucosamine 1-phosphotransferase normally do?

adds a phosphate group to a mannose sugar on the galactosidase as a signal to move it to lysosomes.

a cherry red spot is a result of a _____________________________________.

mucopolysaccaridoses

what are pregnant ladies most common eye-related complaint?

dry eye

what causes dry eye in pregnant women?

fluctuations of estrogen and androgen

that decrease the production of natural tears.

symptoms of dry eye in pregnant ladies include...

dryness, irritation, burning, and a gritty feeling

pregnant women also commonly experience thickening of the _________________.

cornea

what causes corneal thickening in pregnant women?

retained fluids, which result in refractive changes

eicosa is greek for ______.

20

eicosanoids

signaling molecules made by oxidation of twenty-carbon essential fatty acids

essential fatty acids

EFAs

what do eicosanoids do?

They exert complex control over many bodily

systems, mainly in inflammation or immunity, and as messengers in the central nervous system

The networks of controls that depend upon eicosanoids are among the most ______________ in the human body.

complex

___________________ derive from either omega-3 (ω-3) or omega-6 (ω-6) EFAs

Eicosanoids

The ω-6 eicosanoids are generally ____________________________; ω-3's are much less so.

pro-inflammatory

The amounts and balance of these _________ in a person's diet will affect the body's eicosanoid-controlled functions, with effects on cardiovascular disease, triglycerides, blood pressure, and arthritis.

fats

Anti-inflammatory drugs such as aspirin and other NSAIDs act by down regulating _____________________ synthesis.

eicosanoid

What are the 4 families of eicosanoids?

1. prostaglandins

2. prostacyclins

3. thromboxanes

4. leukotrienes

the synthesis of eicosanoids depends on the presence of what 4 enzymes?

1) phospholipase

2) prostaglandin

3) 12- lipoxygenase

4) 5- lipoxygenase

functions of eicosanoids

- inflammatory

- anti-inflammatory

- induction of labor

- smooth muscle contraction

- asthma relief

many eicosanoids mediate inflammatory rxns including those produced in the ________________________ of the eye

anterior segment

how is phospholipase A2 activated?

1) receptor mediated/Gprotein

2) mechanical pressure/injury

example: physical blow to the eye

Where is the thyroid gland located?

in the middle of the lower neck, below the larynx (the voice box) and is just above the collarbone

What is the function of the thyroid gland?

to control general metabolic rates by the manufacture and release of two hormones: "triiodthyronine" (T₃) and "tetraiodothyronine" (thyroxine, T₄).

What are the 2 primary pathologies associated with thyroid disease?

1) graves disease

2) hypothyroidism

graves disease

most common form of hyperthyroidism. often has ocular effects

hypothyroidism

no ocular effects. metabolism is decreased. patient is lethargic and may experience weight gain.

what is the principal effect of T4 and T3?

stimulate metabolic rates

please read these next cards, they are important

please read these next cards, they are important

hypothalamus

region of the brain releases thyrotropin-releasing hormone (TRH) when it detects low levels of thyroid hormones (mainly thyroxine or T4 and triiodothyronine or T3) in the blood. TRH is then transported to the pituitary gland.

pituitary gland

In response to TRH, the pituitary releases thyroid-stimulating hormone (TSH) into the bloodstream. TSH signals the thyroid gland to produce more T4 and T3 hormones.

thyroid gland

responds to TSH by producing and releasing T4 and T3. These hormones regulate metabolism, energy production, and overall growth and development in the body.

the relationship between the pituitary gland, hypothalamus, and thyroid gland regarding thyroid hormones is best described as...

a feedback loop

What effect do thyroid hormones have on their target tissues?

increase in:

- cardiac output

- ventilation

- food intake

- mobilization of carbs, proteins, and fats

- CO2 output

- urea output

- renal function

- sweating

decrease in:

- muscle mass

- adipose tissue

really read this next card

really read this next card