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What type of enzyme is aldose reductase an example of?
What metabolism is aldose reductase linked to?
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?
What enzyme works with aldose reductase in the polyol pathway?
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?
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)?
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?
- 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?
What are the classes of lipids?
- fatty acids
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?
- 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?
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?
- 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?
What percent of membrane is made up of cholesterol in rod disc membrane?
What is the role of cholesterol in the retina?
- 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
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
What are cell membranes made of?
- 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?
- 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?
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?
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
- 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
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?
How many kcal/gram do tryglycerides (fats) have?
How many kcal/gram do proteins have?
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?
Name four monosaccharides
What is the structure of a pyranose and which monosaccharides are under this category?
- 6 membered ring
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)
- 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?
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?
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
- 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
- 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