-
What type of enzyme is aldose reductase an example of?
Mechaelis-Menten enzyme
-
What metabolism is aldose reductase linked to?
carbohydrates
-
What is the function of aldose reductase?
- oxidative prevention mechanism
- osmotic regulator
- cataract formation in diabetics and patients with galactosemia
-
What family of enzymes does aldose reductase belong to?
aldo-keto reductases
-
What enzyme works with aldose reductase in the polyol pathway?
NADPH
-
What intermediate products does aldose reductase and NADPH make from glucose and galactose?
sorbitol and galactitol
-
What do sorbitol and galactitol cause an imbalance in? What does this cause?
- osmotic imbalance
- lens cells to swell and burst
- cell debris causes a cataract
-
What is the usual glucose Km?
100 mM
-
What cause activation of aldose reductase?
high glucose levels (20 mM) in the lens of eye
-
What are some inhibitors of aldose reductase?
- Quercitin (weak)
- Sorbinil (hypersensitivity)
- Tolrestat (?)
- none are FDA approved
-
What is required for the catalytic site of matrix matalloproteinase (MMP)?
zinc
-
What is the function of matrix metalloproteinase (MMP)?
- involved in the breakdown of extracellular matrix
- break down collagen
- remodel axial length in myopia
- destroy corneal collagen in alkali and other chemical burns
- hydrolyze great variety of extracellular proteins
-
What is the best and worst thing about matrix metalloproteinase (MMP)?
large amount of overlap in what proteins it can break down
-
What scientists have done studies on effects of MMP?
- Rada
- Guggenheim and McBrien
-
What is the role of gelatinase A in eye formation?
- lenghthening the eye ball
- specifically partially digests scleral protein so new proteins can be formed
-
What can inhibit MMP function in alkali or chemical burns?
- synthetic inhibitor of mettaloproteinase (SIMP)
- tissue inhibitor of mettaloproteinase (TIMP)
-
What may be the function of finding better MMP inhibitors?
prevention of glaucoma or other degenerative diseases
-
What are the Amphipathic properties of lipids?
- hydrophobicity
- hydrophilicity
-
What are the classes of lipids?
- fatty acids
- triacylglycerols
- phospholipids
- isoprenoids
- esters
- eicosanoids
- glycolipids
-
What is the structure of fatty acids?
- 3-30 carbon chain (varies)
- hydrocarbons with carboxylic acid group at one end (hydrophilic)
-
What are the characteristics of fatty acids determined by?
- chain length
- degree of unsaturation
-
What characteristics does a long fatty acid chain have?
- hydrophobic
- higher melting point
-
What characteristics does a high degree of unsaturation fatty acid have?
- low melting point
- more fluid
-
How do you determine IUPAC names of fatty acids?
- first # = number of carbons
- # after colon = number of double bonds
- #in parentheses = carbon number closest to carboxylic acid group (COOH) with double bond
-
What are some examples of fatty acids?
- Myristic acid (saturated, sweet smelling)
- Cervonic acid (found in membranes of retinal photoreceptors)
-
How do fatty acids affect biological membranes?
- increasing carbon length raises melting point and thickens membrane
- increasing double bonds lowers melting point and increases fluidity
-
What is the structure of Tryacylglycerols?
- a glycerol and 3 fatty acids esterified together
- liquid form
-
How are lipids and Acetyl CoA related?
lipids can be broken down to form acetyl CoA
-
What lipid is the main source for acetyl CoA formation?
triacylglycerols
-
Does the eye maintain a substantial amount of triacylglycerols for energy production?
No. It only holds a limited amount for maintaining cellular membranes
-
What is the structure of phospholipids?
- similar to triacylglycerols
- (glycerol is frame)
-
What is lipid most important for formation and maintenance of cell membranes?
phospholipids
-
Phospholipid bilayer
- if you don't know what this does, you don't belong in optometry school... but here is a reminder...
- fatty acids face each other
- lipids face aqueous
-
What are cardiolipins?
a variation of phospholipids found in the mitochondrial membranes
-
What is the difference between red blood cell membranes and rod outer segment membranes?
- RBCs need to be more rigid than ROS membranes
- there is 6x more cervonic acid in ROS membranes than RBC
-
What is the structure of an isoprenoid? What are members of this group?
- lipid made from isoprenes (5-carbon unit)
- cholesterol and allied steroids (cortisol)
- vitamin A
- coenzyme Q
- essential oils in plants
-
What are some important things about cholesterol?
- source of cholesteryl esters
- precursor to steroid hormones
-
What is choleseryl ester important for?
precorneal tear film
-
What is cholesterol's function in plasma membrane?
rigidity
-
What percent of membrane is made up of cholesterol in rod disc membrane?
8%
-
What is the role of cholesterol in the retina?
- Nothing
- if found, it confirms ocular disease
-
What are Chalazia?
- granulatmatous inflammation of eyelid margin
- not caused by meibomian glands but is from membranes of neutrophils, lymphocytes, and other WBCs
-
What are the lipids found in chalazia made of?
rich in cholesterol, not cholesteryl esters
-
What are waxes made of?
- esters of long-chained fatty acids and long-chained alcohols
- solid at room temperature
-
Where are waxes found in nature?
- Eye: lipid layer of the precorneal tear film
- leaves
- beeswax
- skin
- hair
- wool
- fur
-
Where are glycolipids important?
membranes of nervous, ocular, and other tissues
-
what are glycolipids?
- lipids containing carbohydrates
- ex. galactose, N-acetylgalactose, and N-acetylneuraminic acid
-
What is function of cell membrane?
- barrier of cell surface and interior cell structures
- hydrophobic
-
What are cell membranes made of?
- lipids
- carbohydrates
- proteins
- phospholipids (make associations more complex)
-
What is a micelle?
- a congregation of lipids forming a spherical structure
- hydrocarbons will face towards each other
-
What lipids are found in cell membranes?
- phospholipids
- cholesterol
- glycolipids
- polar group extends toward aqueous
- nonpolar group associate together hydrophobically
-
What is function of glycolipids in cell membrane?
- part of overall bilayer structure
- contribute short-chain carbohydrates into the outer aqueous volume
- form cellular glycocalyx
-
What forms the cellular glycocalyx?
- complex lipids with short sugar arms
- plasma membrane
-
What is function of lipids in plasma membrane?
the "wall"
-
What is function of proteins in plasma membrane?
- the "doors," 2 types
- intrinsic (integral)
- extrinsic (peripheral)
-
What is function of intrinsic membrane proteins?
- cross the membrane bilayer
- transport (glucose)
- receive (insulin)
- transduction (light)
- attachment (basement membranes)
- Ocular example: rhodopsin
-
What is function of extrinsic membrane proteins?
- only on one side of membrane
- structural (cytoskeleton maintenance)
- anchoring (glycocalyx components)
- transduction, signaling, local movement (myosin and actin components)
- Ocular example: transducin
-
What is function of rhodopsin?
convert light signals into chemical signals
-
Function of carbohydrates in the cell membrane
- smallest percentage of membrane constituents
- mostly found of extracellular surface
- form the glycocalyx
- types: glycolipids and glycoproteins
-
What are the roles of carbohydrates in the plasma membrane?
- immunological identifiers
- biological bridges/ bonding agents (ex. epithelial corneal cells to Bowman's membrane
-
What are the 3 types of transport in cell membrane?
- simple diffusion
- passive facilitated diffusion
- active facilitated diffusion
-
Explain simple diffusion
- used by small molecules, oxygen, nitrogen, pharmacological drugs
- travel from high to low concentration
- substance must be partly lipid soluble (bilipid membrane not a barrier)
-
Explain passive facilitated transport
- protein acts as a channel to move substance across membran
- travel high to low concentration
- can move faster than diffusion
- water transported this way through aquaporins
- glucose uses protein GLUT-1
-
Explain active facilitated diffusion
- proteins act as mechanism to move substances
- uses energy (pumps)
- travel from low to high concentration
- Na+, K+ ATPase pump is good example
-
What are the types of transport?
- uniport (single substance transported)
- cotransport (2 substances transported simultaneously), 2 types
- symport (same direction)
- antiport (opposite direction)
-
What are the layers of the precorneal tear film? (Don't think emulsion, like for anatomy class)
- lipid layer (most anterior)
- aqueous layer (central)
- mucus layer (most posterior)
-
What is the composition of the lipid layer of the precorneal tear film?
-
What is the composition of the aqueous layer of the precorneal tear film?
dissolved salts and proteins
-
What is the composition of the mucin layer of the precorneal tear film?
mucoid proteins
-
what is function of the lipid layer of tear film?
- flow from ducts to eyelid edges
- form a film over the aqueous layer
- adhere to the eyelid skin
- barrier to aqueous layer
- form water-tight seal when lids are closed
-
What is meibomian gland dysfunction?
- excessive production of keratin in ductal epithelium
- epithelial cells detach from gland and block flow
- bacteria infection may result
-
What is role of lipids in photoreceptors?
- transduction mechanism of converting light energy into electrical signaling
- sending signals to the brain
-
What is function of cervonic acid in retina and photoreceptors?
- gives fluidity to cell membranes
- decreases viscosity in membrane discs
- helps with rotational and lateral movements of rhodopsin
-
Photoreceptor percentage of phospholipids is....
- similar to nervous tissue
- has less sphingomyelin and phosphotidyl inositol compared to nervous tissue
-
What is percent of lipid content in photoreceptors?
15%, most cells have only 1%
-
What are polyunsaturated fatty acids vulnerable to?
oxidative processes in retina
-
What prevents destruction of polyunsaturated fatty acids in the retina?
- vitamin E
- it is lipid soluble
- absorbs free radicals which attack double bonds of membrane fatty acids
-
What causes Tay-Sachs gangliosides?
hexaminodase A deficiency
-
What is a symptom of Tay-Sachs gangliosides accumulation?
- cherry red spot on retina
- blindness occurs early
- death at 3-6 years of age
-
What class of lipids does Vitamin A belong to?
-
What are four forms of Vitamin A?
- retinyl ester
- retinol
- retinal
- retinoic acid
-
What are dietary sources of Vitamin A?
- beta carotene (yellow vegetables -- carrots and sweet potatoes)
- retinyl esters (animal sources)
-
What is pathway of Vitamin A from gut?
- beta carotene or retinyl esters are converted into retinol
- chylomicra transports retinol to liver or cell for storage
- retinol changed to retinyl ester for storage
- retinol binds to retinol binding protein (RBP) in cell or prealbumin in bloodstream
- retinal binds to opsin to form rhodopsin or retinoic acid makes glycoproteins in corneal epithelium
-
What is caused by Vitamin A deficiency and in what order?
- Nyctalopia (loss of night vision)
- Xerophthalmia (dry eyes, hardening of conjunctiva)
- Keratomalacia (degeneration of cornea)
-
What are nonocular vitamin A deficiency problems?
- adverse affects to any epithelial cells
- inhibition of bone elongation
-
What does Vitamin A excess cause?
- abdominal pain
- blurred vision
- drowsiness
- headache
- irritability
- nausea
- vomiting
-
What causes Vitamin A excess?
- increased gluconeogenesis
- protein turnover
-
What are recommended levels of Vitamin A for different people?
- children 400 RE
- males 1000 RE
- females 800 RE
- nursing females 1200 RE
-
What is International Units of Vitamin A related to Retinol Equivalents?
3.33 to 1
-
What is the first law of thermodynamics?
energy can be neither created nor destroyed but can be transferred in or out of a system
-
How many kcal/gram do carbohydrates have?
4 kcal/gram
-
How many kcal/gram do tryglycerides (fats) have?
9.3 kcal/gram
-
How many kcal/gram do proteins have?
4.0 kcal/gram
-
How many kcal/gram do alcohols have?
7.0 to 7.2 kcal/gram
-
What is chemical process of energy production?
O2 + some energy molecule yields CO2 + H2O
-
What does respiratory quotient mean?
it is the ratio of CO2 produced compared to amount of O2 used.
-
What are the respiratory quotients of carbohydrates, proteins, and fats?
- carbohydrates 1.0
- proteins 0.8
- fats 0.7
-
What molecule do red blood cells (RBCs) and neurons exclusively depend on for energy?
glucose
-
Name four monosaccharides
- glucose
- galactose
- mannose
- fructose
-
-
What is the structure of a pyranose and which monosaccharides are under this category?
- 6 membered ring
- glucose
- galactose
- mannose
-
What is the structure of a furanose sugar and which monosaccharides are in this category?
-
What 3 forms do monosaccharides come in?
- Aldehyde (least common)
- alpha
- beta (most common)
-
What is the structure of maltose?
- 2 alpha glucose molecules
- linked at 1-4
-
What is the structure of sucrose?
- 1 alpha glucose and alpha 1 fructose
- linked at 1-2
-
What is the structure of lactose?
- 1 beta galactose and 1 beta glucose
- linked at 1-4
-
Where does digestion of carbohydrates start?
- the mouth (buccal cavity)
- saliva has alpha-Amylase
-
What are the properties of alpha-amylase (enzyme in saliva)?
- active at 6.5 to 7 pH
- denatured in stomach
- helps keep teeth clean
- digests monosaccharides or starch
-
Why could radiation therapy for cancer cause cavities?
it can destroy salivary glands
-
What are the attributes of lysozyme?
- attacks peptidoglycan of bacterial cell wall
- attacks gram positive bacteria only
- normal flora is resistant to it
- animals use saliva as antiseptic
-
Where does digestion of proteins start?
stomach
-
What are the properties of gastric juice?
- pH close to 2.0
- kills most microorganisms
- denatures proteins
- required for action of Pepsin (which works at a low pH)
-
Why is the stomach not completely necessary?
the small intestine creates more digestive enzymes with the same function as gastric juice and pepsin
-
Where are trypsin, chymotrypsin, elastase, carboxypeptidase A, and carboxypeptidase B made?
the pancreas
-
What is needed in order to break down triglycerides (fats)?
- break down of large droplets into small ones
- this is done by combination of pancreatic lipase and colipase
-
What substances require bile salts as emulsifiers?
- fatty acids
- 2-monoacylglycerol
- cholesterol
- fat soluble vitamins (A, D, E, & K)
-
What percentage of energy molecules is digested in the human body?
- fats and lipids 95%
- starch and carbohydrates 70%
- proteins variable
- plant polymers not digested
-
Why are proteases and phospholipases secreted in inactive forms?
they can digest the cells that secrete them
-
What is anabolic activity?
- biosynthetic process to synthesize macromolecules
- requires energy
-
What is catabolic activity?
- degradative process
- nutrients oxidized to supply energy for cellular activity
-
What is feedback inhibition?
a chemical reaction pathway is shut off when enough of end product is produced
-
What is "feedforward" stimulation?
- positive feedback loop
- a product stimulates more of a chemical reaction pathway
-
What is glycogen?
- storage form of glucose
- glucose cannot be stored in cells
-
Where is glycogen abundantly present?
-
What is an average fasting glucose level?
- 4 to 5.5 mmol/liter
- same as 70-100 mg/dL
-
What cells in the eye store glycogen?
- corneal epithelium
- retinal Muller cells
-
What is end product of glycolysis?
2 molecules of pyruvate per glucose molecule
-
What is final common pathway for all nutrients?
- formation of acetyl CoA
- TCA
- oxidative phosphorylation
-
Reaction of pyruvate into lactate
pyruvate + NADH + H + lactate dyhydrogenase = lactate + NAD+
-
How much ATP is yielded in anaerobic pyruvate reaction?
2 ATP per glucose molecule
-
What tissues in body use anaerobic pyruvate pathway?
- ocular tissue
- muscle tissue
-
What tissues in body use anaerobic glycolysis?
- mature red blood cells (RBCs)
- skeletal muscle during vigorous exercise
- ischemic tissue cut off from blood supply (like corneal epithelium)
-
What is effect of contact lens wear on corneal epithelium?
- 80% of glycogen used up in 8 hours of wear
- results in corneal edema (increase in corneal thickness)
-
What enzyme does mitochondria posses to perform oxidative phosphorylation?
pyruvate dehydrogenase complex
-
What is function of pyruvate dehydrogenase?
catalyze formation of Acetyl CoA
-
What are the products of the Krebs Cycle?
-
What reactions form energy in Kreb Cycle? (numbers)
-
What is basic process of oxidative phosphorylation?
- Complex I receives NADH for electrons
- Complex II receives FADH2 for electrons
- Q shuttles e- from complex I or II to complex III
- C shuttles e- from complex III to complex IV
- O2 and H+ form water
- Complex V takes H+ and ADP to form ATP
-
What is total yield of oxidative phosphorylation?
36-38 ATP per glucose molecule
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