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566 Cards in this Set

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Which vitamin deficiency causes scurvy?
Vitamin C
Presentation of Celiac Sprue
- Gluten sensitivity that leads to flattened intestinal villi and the intestine is not able to absorb water
- loose, foul-smelling stools
Adrenal glands and laukocytes release what vitamin during stress?
Vitamin C
Cortisol production is dependent on what vitamin
Vitamin C
What does Cortisol due in terms of metabolism. What vitamin enables this?
Cortisol induces gluconeogenesis from glycogen and proteins in response to stress. Vitamin C enables its production.
which vitamin deficiency causes Beri Beri
Thiamine B1 deficiency
Which vitamin deficiency leads to Rickets?
Vitamin D
Keratolytic

What drug is keratolytic?

What vitamin is it derived from?
helps to stop overgrowth of keratinocytes

Accutane - Acne Drug

Vitamin A - all trans form
What is Wernicke-Korsakoff encephalopathy? What vitamin deficiency causes it?
paralysis of eye movemnts, ataxia, and mental confusion


Thiamine B1
Which vitamin is essential for FAD production?
Riboflavin B2
NAD production requires what vitamin?
Nicotinamide = niacin = B3
What are the four Ds of Pellagra?
Dementia, Dermatitus, Diarrhea, Death
What vitamin is used to treat Pellagra?
Nicotinamide = Niacin = B3
Which vitamin is a cofactor for transaminase reactions, neurotransmitter synthesis, glycogenolysis, steroidogenesis and is a treatment for PMS?
Vitamin B6 - pyridoxal phosphate
Which vitamin is synthesized from tryptophan and used to treat hypertriglyceridemia?
Vitamin B3 = niacin = nicotinamide
The deficiency of either of what 2 vitamins causes macrocytosis
Vitamin B9 - Folic Acid and
Vitamin B12 - cyanocobalamin
Tetrahydrofolate is another name for what vitamin?
Vitamin B9 Folic Acid
A deficiency of what vitamin leads to pernicious anemia?
Vitamin B12 - cyanocobalamin
What stomach secretion is neccesary for absorption of Vitamin B12. What results from malabsorption?
Intrinsic Factor from the parietal cells.

Pernicious Anemia will result.
What vitamin is the cofactor in the methylation of proprionate to succinate via methyl malonate?
Vitamin B12 - cyanocobalamin
Vitamin B12 is AKA
cyanocobalamin
How does Lovastatin function.
It resembles HMG-CoA and inhibits HMG-CoA reductase, the rate limiting step in denovo cholesterol synthesis.

HDL thyen scavanges cholesterol to meet the needs of the cell.
Describe the SREBP pathway and how it responds to Sterol concentration.
Inthe presence of cholesterol or oxysterols, SREBP scap is retained int he ER by binding to Insig. Inthe absence of insig it is reraleassed from the membrane in the golgi apoparatus. SREBP reaches the nucleus and increases transcription of HMG-CoA reductase.
Prothrombitic arachodonic acid is found in pletelets of americans who ate more of what fatty acid?
Omega 6
Linolenic is omega?
3
Linoleic is omega?
6
Which fatty acids are essential to human life?
Linolenic (omega 3) and linoleic (omega 6) acid
Pancreatic Lipase converts triacylglycerol to what?
2-Monoacyl glyceral via 2 consectuvie hydrolase reactions.
Sphingo myelin consists of a backbone, a fatty acid and what other groups?
Phosphatidyl Choline
how does glycolipid compare to sphingomyelin?
glycolipid contains a carbohydrate group in place of phosphatidyl choline.
Describe the generic process of triacylglycerol ingestion and digestion.
1.) TGs are emulsified by bile salts fromt he pancreas.
2.) Pancreatic lipase converts TGs to 2-monoacylGlycerol and Free fatty acid
3.) Nascent chylomicrons regenerated TGs and attach Apoprotein B and phospholipids in the lymph
4.) Mature chylomicrons enter the blood stream.
Bile salts absorbed int he small intestines are returned to the gall bladder by which route?
The hepatic protal vein.
Why does 2 monoacylglycerol and free fatty acids need chylomicrons for transport?
They are hydrophobic and need carriers in order to transport in an aquatic environment.
What is the major lipoprotein of the chylomicron?
Apoprotein B-48 (48%)
What does HDL provide tot he chylomicron?
ApoProtein E and Apoprotein CII
What is Apoprotein E's function?
ApoE is recognized by receptors on cells which trigger endocytosis of chylomicrons. (particulalry liver)
Which apoprotein is a membrane receptor for chylomicron endocytosis?
ApoE
What is the function of ApoC II
Activates Lipoprotein Lipase which is found in capillary epithelium and digests the triglycerides of chylomicrons and VLDL
Are all LPL's the same?
No different tissues have different isozymes with different Km's to Tgs
how do fat cell's LPL compare with skeletal muscle cells' LPL
Fat cells LPL has a higher Km for TGs
How are fatty acids utilized by peripheral tissues?
Fuel via B-oxidation and as components for lipid synthesis and maintenance.
Where are chylomicrons synthesized?
Intestinal epithelial cells.
Cholesterol
main component of membranes and lipoproteins and is the precrusor for bile salts and steroid hormones.
How much cholesterol will you find in vegetable oil?
None! It is from egg yolks and meat products.
List the intermediates of de-novo Cholesterol biosynthesis
A Heavier mate is great for sex... Loves Cock.

Acetyl and acetoacetyl CoA
HMG-CoA
Mavalonate
Isopentyl pyrophosphate
Geranyl pyrophosphate
Farnesyl payrophosphate
Squalene
Lanosterol
Cholesterol
HMG-CoA reductase performs what reaction.
HMG-CoA to Mevalonate
via 2NADPH


(The rate limiting step)
List the 3 means of regul;ation for HMG-CoA
1.) Phosphorylation deactivates
2.) Transcription of HMGCoa Reductase (SREBP pathway)
3.) Proteolysis
how are cholesterol esters formed.
The 3C hydroxyl moeity is esterified by Lecithin:Cholesterol Acyltransferase (LCAT) or acyl:cholesterol acyltransferase (ACAT)
What is the difference between ACAT and LCAT?
ACAT is in tissue cells and sequesters cholesterol for use in steroid hormone production

LCAT is found in blood and utlilizes HDL bound cholesterol as substrate.
Where is Lipoprotein lipase found? what does it do?
Endothelial cells of blood cappilaries

it hydrolyzes triglycerides and depltes the remnant chylomicron of triglycerides.
What is Hepatic Lipase? What does it do?
also known as HTGL; it converts IDL to LDL
What secretes VLDL into the bloodstream?
The liver
What is more predominant in VLDL? Triglcerides or Cholesterol?
Triglycerides are 5 x more than cholesterol
What proteins are found in VLDL
ApoB-100, Apo CII, Apo E,
what lipoprotein is capable of removing cholesterol from the body?
HDL - removes cholesterol from membranes and converts them to cholesterol esters via LCAT which is activatede by apoA.

The cholesterol esters are transfered to VLDL which is endocytosed by the liver and released as bile.
What gived HDL its density?
A high protein content.
What protein enables transfer of cholesterolfrom cell membranes to HDL?
ATP-binding cassette 1
What is the key enzymatic step of cholesterol excretion?
7-alpha hydroxylase
Explain Tangier Disease
mutation in ATP binding cassete 1 leads to cholesterol buildup.

premature atherosclerosis and CV disease. yelloworange tonsils!
how does conjugation affect bile salts?
It lowers their pK and therefore makes them better detergents.
What do elevated levels of Lp(a) correlate with?
Cardiovascular disease
familial hypercholesterolemia is caused by a mutation in what receptor?
LDL
In familial hypercholesterolemia, why may triglyceride levels be normal while cholesterol levels skyrocket?
LDL is depleted of tiglycerides
in familial hypercholesterolemia, what is the most important enzyme regulation which is lost?
HMG-CoA reductase is inhibited by cholesterol uptake by LDL receptor. With a malfunctioning LDL receptor, De novo Cholesterol synthesis will occur. leading to an even higher level.
Where do LRP receptors exist? What do they bind?
Present in the Liver and Brain, they bind apoprotein E and therefore remnant chylomicrons and VLDL. They also bind alpha-2macroglobulin and tissue plasminogen activator
Macrophage Scavenger Receptor
bind oxidized LDL - uptake of oxidized LDL by macrophages is the first step in the genesis of atherosclerotic plaques.
What is the first step in the generation of atherosclerotic plaques?
Uptake of oxidized LDL by macrophages.
What are foam cells?
Macrophages loaded with oxidized LDL
what inhibits formation of foam cells?
vitamin C, E, and A (antioxidants)
Name 5 pharmacological interventions which reduce plasma choesterol
1.) Statins - inhibit HMGCoaReductase

2.) Bile acid residues stimulate excretion of bile salts

3.) Niacin activate LPL, reduces hepatic VLDL, reduces HDL catabolism

4.) Fibrates - PPAR alpha antagonist reusults in reduced lipid biosynthesis, increased LPL ctivity, and increased ApoA production

5.) Ezetimibe - reduces intestinal absorption of dietary cholesterol.
How does Niacin lower plasma cholesterol?
It activates LPL and reduces hepatic production of HLDL while also reducing the breakdown of HDL.
Abetaliproteinemia
defective assembly of lipoproteins involving Apo B. Malabsorption occurs with triglycerides being builtup in intestinal cells.
Autophagy
self eating - a cell can eat its components to release nutrients for the cells use. (source of fatty acids)
Differentiate between the purpose of Mitochondrial, Peroxisomal, and Smooth ER oxidation of fatty acids.
Mito- small FAs
PEroxisomal - breaks down to small FAs

SER - breaks down branched FAs
What is considered the major problem in type II diabetes? Hyperglycemia or lipotoxicity?
Lipotoxicity -
how much sugar is in a can of coke?
Alot - (10 sugar cubes!)
what histological effect will occur with inadequate choline in TPN?
Fatty liver - phosphatidyl choline is an essential metabolite in fatty acid breakdown.
What are MUFAs used for?
Monounsaturated Fatty Acids are used for triglyceride and phospholipid synthesis.
What 3 Major tissues in the body secrete fat?
Liver, Small Bowel, Mammory Glands
What are fatty acids bound to when traveling in the blood?
Albumin
Is the accumulation of triglyceride as lipid droplets in cells a bad thing?
No, they are inert and seuester the fat which prevents lipotoxicity.
What builds up in patients with methylmalonic acidemia which could be mistaken as ethylene glycol if you are trained as a biologist and allowed to use a chemists equipment.
propionic acid.
What are MUFAs used for?
Monounsaturated Fatty Acids are used for triglyceride and phospholipid synthesis.
What 3 Major tissues in the body secrete fat?
Liver, Small Bowel, Mammory Glands
What are MUFAs used for?
Monounsaturated Fatty Acids are used for triglyceride and phospholipid synthesis.
What are free fatty acids bound to when traveling in the blood?
Albumin
What 3 Major tissues in the body secrete fat?
Liver, Small Bowel, Mammory Glands
Is the accumulation of triglyceride as lipid droplets in cells a bad thing?
No, they are inert and seuester the fat which prevents lipotoxicity.
What builds up in patients with methylmalonic acidemia which could be mistaken as ethylene glycol if you are trained as a biologist and allowed to use a chemists equipment.
propionic acid.
What are free fatty acids bound to when traveling in the blood?
Albumin
Is the accumulation of triglyceride as lipid droplets in cells a bad thing?
No, they are inert and seuester the fat which prevents lipotoxicity.
What builds up in patients with methylmalonic acidemia which could be mistaken as ethylene glycol if you are trained as a biologist and allowed to use a chemists equipment.
propionic acid.
What is the process which is affected in methylmalonic acidemia. What builds up?
The conversion of amino acids into succinyl coA is blocked leading to buildup of th eintermediates methylmalonic acid and propionic acid.
A defect in what cofactor synthesis or absorption causes MMA? Why?
Cobalamin (Vitamin B12) - it is essential for the function of methylmalonyl-CoA mutase.
How do you treat MMA
dietary restiction of most protein! + Glucose
How does ethylene glycol poisoning occur?
the oxidation products (not ethylene glycol itself) glyoxal --> oxalic acid.
Why is ethanol used to tret ethylene glycol poisoning?
ethylene glycol is converted to glyoxal via alcohol dehydrogenase. Ethanol is also processed by Alcohol Dehydrogenase, so ethanol acts as a competitive inhibitor.
why is oxalic acid bad?
It crystalizes in the presence of calcium. This occurs in the kidneys.
Why would you see hypocalcemia in ethylene glycol poisoning?
calcium binds oxalic acid and forms crystals in kidneys.
How are triglycerides transported to peripheral tissues?
via VLDL
Pancreatic Lipase
Released into Small intestine and digests dietary triglyucerides with are emulsified by bile salts.
Lipoprotein Lipase
found on cell membranes of endothelial cells. Digests triglycerides associated with liporoteins (chylomicrons, VLDL and IDL)

Activated by Apo C
HTGL (hepatic Lipase)
Found on the membrane surface of liver cells. Digests IDL triglycerides and contributes tot he production of LDL.
Hormone Sensitive Lipase
Regulated by insulin (deactivate) and Glucagon (activate). Low Isulin/glucago leads to increased cAMP which stimulates PKA, which phosphorylates hormone sensitive lipase.

Hydrolyzes triglycerides in fat cells as well as lipid droplets in muscle cells.
Long chain fatty acids which are converted to acyl CoA must undergo what aditional step to reach the mitochondria for b-oxidation?
They must be converted to long chain acyl carnitine
what are the four fundamental steps of b-oxidation at the beta carbon?
1.) Dehydrogenation of a single bond to double bond

2.) Hydration - additonal of water to produce an alcohol at the beta carbon

3.) Dehydrogenation to forma ketone

4.) Cleavage
What enzymes catalyze the four fundamental steps of b-oxidation?
1.) Acyl-CoA dehydrogenase
2.) Enoyl CoA hydratase
3.) B-hydroxy acyl CoA dehydrogenase
4.) B-keto thiolase
MCAD deficiency affects what step of b-oxidation.
The first step in medium chain b-oxidation. it is a deficiency in Medium chain Acyl-Coa dehydrogenase.
Which steps in b-oxidation lead to the production of ATP.
Step 1 = 2ATP
Step 3 = 3ATP

(The two dehydrogenases!)
What additional enzymes are needed for b-oxidation of unsaturated fatty acids?
Monounsaturated = enoyl CoA isomerase

Polyunsaturated = enoyl CoA isomerase and 2,4 dienoyl CoA reductase
What occurs in Zellweger's syndrome?
genetic defect prevents localization of peroxisomal proteins. - leads to a buildup of very long chain fatty acids particularly in brain tissue.
What does alpha oxidation do? Why must phytanic acid undergo alpha oxidation?
alpha oxidation removes hte alpha carbon as CO2.

Phytanic acid msut undergo alpha oxidation because the beta carbon is blocked by a methyl group.
In addition to acetly CoA what is released in the b oxidation of phytanic acid?
Propionyl CoA - due to the presence of methy branching.
What organ predominately produces ketone bodies?
The liver
HMG-CoA lyase leads to the production of what?
acetoacetate and therefore acetone (ketone bodies)
What is the rate limiting step of fatty acid synthesis?
Conversion of acetyl CoA to malonyl CoA by Acetyl CoA carboxylase
How do they following metabolites affect Acetyl CoA Carboxylase?

1.)Citrate
2.)Palmitoyl CoA
3.)AMP - protein kinase phosphorylation
4.) insulin
1.) citrate - activates
2.) palmitoyl CoA - inhibits
3.) phosphorylation - inhibits
4.) insulin leads to less phosphorylation - acitvates
Characterized by dryness of the conjunctiva and cornea of the eye. Long term effects can lead to eye ulceration and blindness. Termed "Night blindness"

What is this condition and what causes it?
Xeropthalmia - Vitamin A deficiency
What molecule donates 2 carbon unites to fatty acid synthase?
Malonyl CoA
Fatty Acid Synthase creates a 16 carbon fatty acid called?
Palmitic acid.
What is used for reduction reactions following the addition of each 2 carbon subunit during the production of palmitic acid?
NADPH
What does carnitine palmitoyl transferase do?

What inhibits it?
Shuttles fatty acids into the mitochondria for beta oxidation.

Inhibited by malonyl-CoA levels during conditions favoring fatty acid synthesis.
What is interesting about the dimer nature of fatty acid synthase?
Two Fatty acids can be synthesized simultaneously
What cofactor is neccesary to convert acetyl coA to malonyl CoA?
Biotin
What is the predominant fatty acid component of biological membrane systems while also being the precursor of eicosanoids?
Arachadonic acid
Why can't the body synthesize arachadonic acid de novo?
Humans cannot forma double bond at the omega end of the 10th carbon from the alpha end of a fatty acid.
Glycerol 3 phosphate and Phosphatidic acid are key intermediates int he production of what? where?
Triglycerides in the liver and adipose tissue.
Ethanolamine can be converted to choline using what enzyme? Describe what the enzyme does?
SAM - methylates 3 times.
Diphosphatidylglycerol is also known as _____________. It is the major phospholipid in what membrane?
Cardiolipin - mitochondrial membrane.
Sphingosine is synthesized by the condensation of what? What is required for this?
Serine and Palmitoyl CoA.

Serine palmitoyl transferase requires pyrodoxal phosphate to function.
Farber's disease
genetic disorder caused by a deficiency in lysosomal acid ceramidase which result sin accumulation of ceramid in tissues.
Which Vitamins are made int he human body?
Vitamin D - sunlight
Vitamin K - microorganisms,
Niacin - Tryptophan
Biotin - microorganisms.
Associate the deficiency syndrome with its deficient nutrient.

1.) Beri-Beri
2.) Pellagra
3.) Scruvy
4.) Pernicious Anemia
5.) Macrocytosis
6.) Neural tube Defects
1.) Beri-Beri - thiamine
2.) Pellagra - niacin
3.) Scruvy - vitamin c
4.) Pernicious Anemia - vitamin b12
5.) Macrocytosis - vitamin b12, folate
6.) Neural tube Defects - folate
how do you test for vitamin deficiency? (2)
1.) Blood Test -folate and vitamin
2.) Stress Test (metabolic vs immune)
Anergy
no immune response to antigen.
Why can Vitamin A treat acne and cancer?
Vitamin A blocks production of keratinocytes.
Psuedo tumor cerebri?
Elevated intracranial pressure due to fat soluble vitamin A overdose. (relatively low dose toxicity)
What vitamin has the smallest theraputic ratio--ratio between RDA and toxicity?
Vitamin A
Vitamin D is made from what steroid precursor?
Ergosterol
What is the only organ that can activate Vitamin D?
Kidney - it is the only organ that has enzymes which 1 hydroxylates vitamin D.
Failure of what organ leads to vitamin D deficiency and consequent phosphate buildup?
Kidney
Ricketts.
Vitamin D deficiency
25 hydroxylation of Vitamin D occurs where?
Liver. (1 hydroxylation is in the kidney)
Which vitamin is interfered by warfarin and antibiotics?
Vitamin K
gamma-glutamyl carboxylase is aided by what vitamin? What process is this?
Vitamin K - clotting
Why is Vitamin E required now but not previously?
Fatty acid - polyunsaturated - intake.

Modern food processing removes vitamin E
Which vitamin is critical in oxidation of steroids to bile acids?
Vitamin C
Reduction of glutathione requires what vitamin?
C
which vitamin hydroxylates lysine. Where does it do this?
Vitamin C - collagen
What stores vitamin C in your body?
Adrenal Gland
Do you need vitamin C when you are sick?>
No, but it is nice to replenish it sooner than later..
Why is ascorbate required in primates when msot is in the genome.
The brain will suck up all of the glucose and starve the other tissues. Using the adrenal stores limits the brains tendency to do this in non stress times.
Wernicke Korsakoff
paralysis of eye movments and mental confusion due to thiamine B1 deficiency.
Name an alpha keto acid?
Pyruvate, (valine, leucine, isoleucine breakdown components.)
White rice is deplete of what vitamin... what disease results?
B1-Thiamine = beri beri
I cant I Cant! - because i have this disease due to my lack of B1
Beri Beri - Thiamine B1 deficiency
FAD is from what vitamin?
Vitamin B2 - riboflavin
MCAD deficiency is treated with what vitamin?
Vitamin B2 - riboflavin - FAD link
Thyroid hormone is associated with?
succinate dehydrogenase.
Pellagra is caused by what?
Niacin deficiency
niacin treats what?
hypertriglyceridemia
The goldberger experiment is worse than a frat initiation. What did it prove?
Pellagra is not contagious. It is a nutritional problem - lack of niacin B3
Aminotransferases and glycogen phosphorylases depend on what vitamin?

Ladies, It also treats PMS! TAKE IT! :) <3 Yaaaaay!

Gentlemen, It helps you remember your dreams! Take this when your GF dumps you because you told her to take this.
Vitamin B6 pyidoxal phosphate.
Thymine methylation requires what vitamin?
Folic Acid
Macrocytic anemia results form what vitamin deficiency?
Folic Acid
What vitamin assists in transfering a methyl group to malonic acid?
Folate and B12 - Cobalamin
Avidin
binds very tightly to biotin - useful in biochemistry
What vitamin is neccesary for coenzyme a sequestration?
B16 - pantothenic acid
the WHO growth chart stands out compared to other growth chart in that it is?
A prospective study rather than a retrospective study. Measures normal growth under recommended feeding patterns. Eliminates variables such as breast fed or not.
Who grows faster? Breast Fed or bottle fed?
Bottle Fed. (breast feeding is good because it controls feeding habits early so they don't grow up to be obese)
Slower weight gain =
Wasting
Slower height gain =
Stunting
How long does it take to double birth weight?
4-6 months.
Name the 4 goals of infant nutrition
1.) meet requirements
2.) teach feeding skills
3.) support internal regulation of intake
4.) Prevent chronic disease
how long should you breastfeed according to WHO?
exclusively 6mo

up to 2 years with supplementation
Solids must be introduced at what age for appropriate feeding skill to be most likely obtained?
6-8 months.
Name the 4 stages of Human Milk
1.) Preterm
2.) Colostrum - more protein, antibodies
3.) Transitional - more fat
4.) Mature (12mo)
Foremilk differs form Hindmilk in that it?
Contains less fat. Short feedings lack the satiating fat of hind milk. Leads to bad feeding behavior.
What vitamin may need to be supplemented during breastfeeding?
Vitamin D (most), Vitamin K, Iron
Infantile Rickets results from ?
Low vitamin D

typically breast milk being substituted for juice.
Cows milk have this kind of protein instead of whey? What is the problem?
Casein based proteins - Curdles + Allergenic

it is also better tasting so babies get all fat.
high renal solute load is common with what type of milk?
cows milk.
What is more important? chronological age or signs of readiness?
Signs of readiness.
Marasmus
Prolonged Protein Energy Malnutrition
Marasmus does what to the body?
leads to villous atrophy in the small intestine which further disrupts future absorption.
Kwashiorkor
Diets low in protein but adequate in other calories. Edema due to decreased colloid osmotic pressure.
If a baby is overweight after breast feeding, would you recommend solids at 4mo age.
No, you should delay so they baby doesnt feed as much,

Give Vitamin D, K, and Iron

If you transition to formula give a good whey casein ratio.
Which EFAs are more active when transformed into eicosinoids?
Omega 6 Fatty acids.
What is the main cholesterol sensor in the cell?
The SREBP pathways.
the SREBP responds to high or low cholesterol?
Low cholesterol (NOT AN EXCESS)
The LXR receptor does what?
Regulates the amount of cholesterol available for bile acid synthesis. Responds to 22-R-hydroxycholesterol and 24-(s)hydroxycholesterol.
Linolenic is omega 3 or omega 6?
Omega 3
Linoleic acid is used to make what molecule which is key to clotting?
Thromboxane.
Lecithan is what subfraction of lipids?
Phosphatidyl choline
Which omega acids are most active eicosinoids?
Omega 6
how does omega three inhibit eicosinoid function?
They are less active competititors.
The leone study proved what?
Increased omega 3 vs omega 6 ratio (canola oil) lowered the risk for repeat cardiac events.

Not increasing omega 3 but decreasing omega 6 compared to omega 3.
SREDP senses cholesterol deficiency more when what is consumed.
omega 6 polyunsaturated fatty acids.
Palmitic Acid is how many carbons... what is its saturation?
16 fully saturated
Palmitoleic is how many carbons... what is its saturation?
16 one double bond 9 carbons form omega end.
Linoleic acid is how many carbons... what is its saturation?
18 - 2 double bonds... one is 6 away from omega.
Linolenic is how many carbons... what is its saturation?
18-3 double bonds... one is 3 away form omega end.
Arachidonic acid is how many carbons... what is its saturation?
20 - 4 double bonds... one is 3 away form omega end.
What is the difference between oleic and elaidic acid?
oleic = cis elaidic = trans.
Cholesterol ester is esterified at what position?
3
Name the 4 common head groups for glycerophospholipids.
Choline, ethanolamine, serine, inositol
What apoproteins are present in the nascent chylomicron?
Apo B-48 and Apo A
What apoproteins are present in HDL?
apoE and apo C2
What does HDL do to the nascent chylomicron when it reaches the bloodstream?
donates ApoE and Apoc2
What does ApoC2 do?
Activates LPL enzyme which releases fatty acids form a chylomicron so they can be absorbed by the tissues.
LPL metabolism of VLDL leads to what?
IDL
Where is LPL in the bloodstream?
embedded in endothelial cells
Hepatic Lipase does what?
Converts IDL to LDL and releases TGs
LPL Km is higher in muscle or adipose tissue?
Adipose tissue
Which is denser IDL or LDL?
IDL (it is intermediate between VLDL and LDL)
Where does the chylomicron remnant go? how is it recognized?
The liver - Apo E
What produces HDL
Liver
How does the triglyceride to cholesterol makeup change through the life of a chylomicron?
NAscent = 75% TG 25% cholesterol

Remnant = 50/50
What apoproteins are in HDL?
ApoC2, ApoA ,ApoE
What plant produces the msot cholesterol?
Lettuce when it is accompanied by meat in a big mac. (plants don't have cholesterol)
What does LCAT do?
Lecithan cholesterol acyl transferace transfers a phosphatidyl choline to the 3 position of cholesterol.
cholesterol synthesis is rate determined by what reaction?
What regulates it?
HMG-CoA to Mevalonic Acid via HMG-CoA reductase.

High cholesterol inhibits HMG CoA reductase
CETP
cholesterol Ester transfer protein

inhibition increases HDL and decreases cholesterol in VLDL. (but it makes disfunctional HDL! bad!)
Where do statins function?
HMG CoA reductase in cholesterol de novo synthesis.
What makes Cholesterol ester? from what>
LCAT - phosphatidyl choline
SCAP
SREBP cleavage activating protein

-blocked by statins, decreasing transcription. No cholesterol synthesis.
7alpha hydroxy cholesterol is what?
an intermediate in the rate limiting step of bile acid synthesis.
Is HMG coA active when phosphorylated?
No - AMP inactivates it via a kinase.
What are the two main non conjugated bile salts?
Chenocholic Acid and Cholic Acid
What activated HMG Coa Reductase?
Insulin activates a phosphorylase which dephosphorylates HMG COA reductast and activates it.
what are the two main conjugated bile salts?
Chenocholic acid becomes Taurocholic acid with taurine and cholic acid becomes glycocholic acid with glycine
Reduction of liver cholesterol synthesis by statinshas what side effect aside from inhibiting hmg-coa reductase? Is this good?
LDL receptors increase to boost cholesterol uptake. - this is good, you dont want too much cholesterol in the blood!
how much of the bile salts are returned to the liver?
95%
Lecithen is the generic name for what?
Phosphatidyl choline.
Cholestyrinine does what?
reduces liver reuptake of bile salts and excretes them in feces.
What is the difference between a lipoprotein and apoprotein.
Lipoprotein is the combination of lipids and apoproteins.
what is Lp(a)
LDL with apoA

(indicates Cardiovascular disease)

-unknown mechanism
Where are chylomicrons synthesized?
Enterocytes
high Lp(a) means what?
Cardiovascualr disease.
What is the ratio of TG to Cholesterol in VLDL?
5/1
Familial hypercholesterolemia is caused by what?
Defective LDL receptor = too much cholesterol in blood
The LDL receptor recognizes what?
ApoB-100 and ApoE
What leads to foam cells?
Oxidation of LDL by superoxide followed by uptake by macrophages.
What limits creation of foam cells in high LDL situations?
Antioxidants. (Vitamins E,C,A)
Scavenger receptors do what resulting in atherosclerosis.
Take in macrophages into the sub intimal layer (below the endothelial cells)

Foam cells form here
Platelets and Monocytes produce what factor that stimulates smooth muscle cell migration and proliferation?
Platelet derived growth factor PDGF
how do we get rid of cholesterol in atherosclerosis?
HDL, ApoA clones, Excretion of bile salts via bile acid resins, Statins, Niacin, fibrates, ezetimibe .
how does niacin reverse atherosclerosis?
Activates LPL, reduces hepatic production of VLDL, reduces HDL catabolism.
how do fibrates lower cholesterol?
Antagonizes PPAR-alpha (result in reduced lipid biosynthesis)

leads to increased LPL activity and increased ApoA production.
How does Ezetimibe lower cholesterol?
reduces intestinal absorption of cholesterol
Why are some CETP inhibitors bad?
They form disfunctional HDL
Abetalipoproteinemia
B-48 or B-100 is reduced, less chylomicrons so you dont get enough Vitamin E and Vitamin A

Leads to Ataxic neuropathy and retinitis pigmentosa.
Free fatty acids in the blood are carried by?
Albumin
What anion binds to fatty acids (insoluble)
Calcium
Autophagocytes?
breakdown own membranes to replace nutrients ( fatty acid)
Where are microsomes found in the human body?
no where!

They are lab artifacts simulating the Smooth ER
What does the liver do to free fatty acids? What if they can't do this?
The liver makes free fatty acids into triglycerides and secretes it (VLDL). If this does not occur, fatty acids are stored as lipid droplets.
Name the 4 major components of VLDL
Triglyceride, Phosphatidly choline, ApoB100, Cholesterol ester,
Choline deficiency will lead to what organ condition?
Fatty liver due to inability to create VLDL.
How do anorexics get fatty livers?
Not enough protein in diet. ApoB cannot be synthesiszed in the liver... no VLDL.
what releases fatty acids form VLDL?
LPL
Nash
nonalcoholic steatohepatitis - free fatty acids lead to cirrhosis of liver.
Insulin does what?
Makes fatty acids into triglycerides
Why is fructose worse than glucose?
Fructose feeds in later so it bypasses the rate limiting step of glycolysis --> straight to fatty acids
What produces most fatty acids and TGs in the liver?
Carbohydrate excess
insulin resistance leads to obesity how?
too much glucose reaches the liver and is stored as fat.
MMA produces what chemical which resembles ethylene glycol to idiots who can't use an HPLC?
Proprionic acid.
What cofactor is required for methylmalonyl mutase enzyme?
Adenosyl cobalamin (from vitamin B12)
A defect in propionyl-CoA carboxylase could cause what syndrome?
MMA
A defect in methymalonyl-CoA racemase could cause what syndrom?
MMA
A defect in absorption of what vitamin can cause MMA?
Vitamin B12
MMA is caused by the inability to produce what in the catabolism of proprionyl-CoA?
Succinyl-CoA
Where does the toxicity from ethylene glycol poisoning come from?
Oxalic acid oxidation product leads to kidney damage. (Blood in urine)
Why is ethanol a treatment for ethylene glycol poisoning?
It competes with the conversion of etylene glycol to glyoxal by alcohol dehydrogenase
Why is oxalic acid a bad thing to have in your blood?
It is insoluble. crystals mess up your kidneys.
what diet is best to treat MMA?
Low amino acids (Thymine, Uracil, Valine, Isoleucine, Methionine, Threonine,), cholesterol, odd chain fatty acids.
compare the concentrations of propionic acid in MMA to ethylene glycol poisoning occuring 3 days before the test.
If the amount of ethylene glycol was mole equivalent to that of propionic acid in MMA, you would need to feed a baby 80 gallons of ethylene glycol!
Why does etylene glycol poisoning lead to hypocalcemia?
Calcium binds to oxalate.
Chylomicrons are synthesized where? where are they released?
Intestinal cell (enterocytes). Released into the lymph where it reaches the blood stream by the thoracic duct.
Insulin has what effect on lipoprotein lipase (LPL)?
activates
HDL supplies what to VLDL?
ApoE and ApoCII
What apoprotein on VLDL activates LPL?
ApoCII
LPL converts VLDL to what? how?
IDL by removing Triglycerides.
Removing tryglycerides from a chylomicron does what to its density?
Increases
VLDL has a 5/1 ratio of TG to cholesterol.

LDL has closer to a 1/1 ratio of TG to cholesterol.

What changes occured to Cholesterol to produce this?
No real change... the difference in ratio is due to a reduction in Triglycerides through processing by LPL and Hepatic Lipase (HTGL
Free LDL can be oxidized... where will this product end up?
Taken up by macrophages forming foam cells in the intima of the blood vessel. (atherosclerosis)
Why is HDL good cholesterol?
It can take cholesterol out of membranes and assist in secretion.
What apoprotein is present on the nascent chylomicron before its interaction with HDL?
ApoB48
What Apoprotein is present on the nascent VLDL before its interaction with HDL?
ApoB100
What is the function of ApoCII
activates LPL
What is the function of ApoE
Receptor mediated uptake of lipoprotiens in the liver.

Activates LDL receptors as well.
ApoA1 does what?
Activates LCAT to trap cholesterol as cholesterol ester
Where is ApoA found?
HDL
Why is LDL bad cholesterol?
It can be oxidized and brought into the cells. Oxidized HDL is less likely to be taken into cells.
Familial hypercholesterolemia is caused by a defective what? Is there a genetic component?
LDL receptor -Yes "familial"
What does the LDL receptor recognize?
ApoE and ApoB100
Vitamins E,C,A do what to Foam cell formation?
Limiting evidence that it prevents oxidation of LDL and therefore reduces foam cell formation.
Where is atherosclerosis most commonly found?
in areas with turbulent flow (aortic arch, biforcation of corotid arteries etc)
compare the amount (g) of fatty acids and glucose in the blood?
Much more glucose than fatty acids.
Compare the caloric use of fatty acids and glucose in the blood over a 12hr period?
Much more fatty acid calories than glucose calories
Hormone sensititve lipase is activated by what two hormones.
epinephrine and glucoagon
hormone sensitive lipase works through what secondary messenger pathway? How does linsulin affect this?
cAMP --> PKA --> Hormone sensitive lipase.

Low insulin stimulates lipase function.
Pancreatic Lipase
Released into small intestine and digests dietary triglycerides that are emulsified by bile salts.
Lipoprotein Lipase
AKA endothelial lipase - found on cell membranes of endothelial cells, digests triglycerides associated with lipoproteins (Chylomicrons, VLDL, IDL) activated by ApoCII
Hepatic Trigliceride Lipase (Hepatic Lipase) (HTGL) (HL)
Found on membrane surface of liver cells. - Digests IDL triglycerides, thus contributing to the formation of LDL
Hormone Sensitive Lipase
Regulated by insulin and glucagon. Low insulin/glucagon increases cAMPlevels --> PKA --> hormone sensitive lipase (acitve)

hydrolyzes triglycerides in fat cells as well as triglycerides in fat dropletes within muscle cells (especially cardiac muscle)
why is there very little free fatty acid inside the cell?
It is bound to acyl-CoA and brought the the mitochondria.

Acyl-Carnitine

(requires ATP)
CPT-1 or Carnitine Acyl Transferase
Carnitine palmitoyl transferase - converts fatty acyl CoA and Carnitine to Fatty AcylCarnitine and CoA so that fatty acids can cross the inner mitochondrial membrane.
What converts Fatty acyl Carnitine to fatty acyl CoA in the mitochondrial matrix?
CPT-II
List the 4 (chemistry) steps of b-Oxidation:
Dehydrogenation

Hydration

Dehydrogenation

Cleavage
B-oxidation creates a shortened fatty acid and what?
Acetyl-CoA
What electron carriers are utilized during beta oxidation?
FADH2 -dehydrogenation (step 1)

NADH - dehydrogenation (step 3)
how does Niacin lower plasma cholesterol?
activates LPL, reduces VLDL production, reduces HDL breakdown
Palmitate creates how much ATP via B-Oxidation? Total metabolism?
28 ATP (7 rounds)

It is a 16 carbon fatty acid.

Total is roughly 129 form the 8 acetyl CoAs... A LOT
Where do we see trans fats generated in our body?
Step 1 -Dehydrogenation- of b-oxydiation forms a trans double bond. It is cleared quickly however.
What does Malonyl CoA inhibit in the beta oxidation process?
It inhibits PCT-1 so you dont get fatty acyl carnitine to pass through inner mito membrane.
What molecule inhibits PCT-1?
Malonyl CoA (blocks B-oxidation)
high NADH and FADH levels will activate or Deactivate b-oxidation?
Deactivate. you need NAD and FAD to perform the dehydrogenase function.
high levels of insulin activates what process which blocks b-oxidation?
promotesacetyl CoA to malonyl CoA. Malonyl CoA inhibits PCT-1
Zellwigger's Syndrome?
Patients do not have normal peroxisomes. No peroxisomal b-oxidation.

deficiencies in hydrogen peroxide production. Stuck with long chain fatty acids.
What process is important for oxidation of very long fatty acids?
Peroxisomal B- oxidation
Peroxisomal B-Oxidation stops when?
at 8 carbons.
FADH2 form peroxisomal B-oxidation is used for what?
making hydrogen peroxide (NOT ATP)
alpha oxidation produces what?
carbon dioxide - it removes the terminal carbon. This is used for branched chain fatty acids. Alternates acetyl-CoA and proponyl-CoA in phytanic acid.
Rustem's Disease
neurotaxic neuropathy with high levels of phytanic acid.

Due to inability to alpha oxidaize fatty acids.
Mevalonic Acid is generated by what enzyme?
HMG-CoA reductase
where does omega-oxidation of fatty acids occur?
Endoplasmic reticulum
What is the end product of omega oxidation of fatty acids? What syndrome is this characteristic of?
Dicarboxilic acids - excreted in the kidney. This is an indicative feature of MCAD deficiency.
HMG-CoA can end up being this if it is not reduced by HMG-CoA reductase?
Acetoacetate (ketone bodies)

later this forms Acetone + CO2 (acid), and D-B hydroxybutyrate. Also ketone bodies.
What tissue metabolizes ketone bodies?
The brain and others.
In fatty acid synthesis, Insulin increases the activity of what three enzymes?
Pyruvate dehydrogenase, Citrate Lyase, Malic Enzyme
Pyruvate dehydrogenase does what in fatty acid synthesis?
Converts Pyruvate to OAA and Acetyl CoA

Citrate is able to leave the mitochondria.
Citrate Lyase does what in fatty acid synthesis?
Converts Citrate back to OAA and Acetyl CoA (ATP dependent)

gets Acetyl CoA out of mitochondria.
Acetyl-CoA carboxylase does what? What cofactor is needed?
converts Acetyl CoA to Malonyl CoA

It needs biotin
Acetyl CoA carboxylase is affected by ATP how?
ATP deactivates it! via a kinase
how does Insulin affect Acetyl coA carboxylase?
Inuslin activates it via a phosphorylase
ACP - acyl carrier proteins form dimers for what benefit?
You cna generate two fatty acids at the same time!
How does fatty acid synthesis relate to beta oxidation?
is it the same general 4 steps in reverse

1.) condensation
2.) Hydrogenation
3.) Dehydration
4.) Hydrogenation
Linoleic acid is necessary for what fatty acid?
Arachidonic acid (20Cs) - the body cannot form double bonds beyond the 10th carbon.
What is the key molecule in triglyceride synthesis?
Glycerol 3-P
What are the key branchpoint intermediates in phospholipid synthesis from triglyceride synthesis?
Phosphatidic Acid and Diacylglycerol
how does Insulin affect LPL?
Activates it. (More triglycerides in adipose cells!)
Lecithen = ________
Phosphatidyl Choline
Ether Glycerolipids: Structure? How do they function?
Contain an ether, a fatty acid, and a phosphate head group.

Function as Plasmalogens and Platelet activating factor.
Platelet activating factor is what kind of lipid?
Ether Glycerolipid (a type of phospholipid)
From what is Phosphatidyl Serine formed?
Serine and Ethanolamine exchange on phosphatidylethanolamine
Name two ways that Phosphatidylethanolamine is formed?
CDP- ethanolamine added to diacylglycerol or decarboxylation of phosphatidylserine.
Name two ways phosphatidyl choline can be synthesized:
CDP-Choline added to diacylglycerol

or

3 methylations of phosphatidylethanolamine via SAM
If I have Phosphatidyl Serine and I want Phosphatidylcholine, how would i synthesize it.
1.)Decarboxylation of phosphatidylserine to phosphatidylethanolamine.

2.) 3 methylations of phosphatidyl ethanolamine.
What nucleotide is essential for the synthesis of glycerophospholipids?
Cytosine (CTP)
Phospholipase A1 A2 C and D differ in their position of cleavage/remodeling in glycerophospholipids. Slam this card with some knowledge!
A1 - position 1 fatty acid
A2 - position 2 fatty acid
C - Phosphate group
D - head group
position 2 in glycerophopsholipids is commonly what phospholipid?
Arachidonic acid - This makes phospholipase A2 improtant for eicosinoid synthesis.
Lysoglycerophospholipid lacks a fatty acid at what position?
2.
If CTP is added first to phosphatidic acid, what two glycerophospholipids can be formed?
phosphatidylinositol and Cardiolipin
If phosphatidic acid is first dephosphorylated, what glycerophospholipids can be formed?
Phosphotidlycholine, Pho..ethanolamine, Pho..Serine
Serine and palmitoyl-CoA are essential for the synthesis of what?
Spingolipids
Cardiolipin is localized where?
mitochondria
Ceramide
structurally similar to diacylglycerol - key to sphingosine production.
Farber's disease
deficiency of lysosomal acid ceramidase. cant convert ceramide to fatty acid. - leads to programmed cell death. - joint
Ceramidase deficiency
Farbers disease
If i have way too much ceramide, what is wrong?
Ceramidase deficiency
What is a potential therapy which uses ceramide.
Balloons loaded with ceramid can destroy plaques via apoptotic factors.
Aside from osteoporosis, how does malnutirion lead to increased hip fracture?
Muscle wasting
how does malnutirion cause edema
Osmolytic imbalance.
Name reasons why caloric intake decreases with age?
Alterations in taste and smell
Satiety occurs more rapidly
does the Antrum of your sotmach stretch more easily or less easily with age? What does this cause?
Less stretching. makes you feel full faster.
How does testosterone affect the elderly?
Testosterone decreases... lead to increase in fat mass and decrease in lean mass.
Testosterone supplementation would do what to fat mass?
decrease fat mass and increase lean mass.
How are leptin and testosterone interrelated?
decreased testosterone leads to increased leptin. High leptin means you feel full faster.
Leptin affects what part of the brain?
Hypothalamus - satiety center
Low levels of leptin would be expected in the obese or the emaciated?
Obese
Leptin does what to smell and taste?
Decreases its sensation (less likely to eat!
What is the most common cause of weight loss in the elderly?
Depression
MEALS ON WHEELS is what?
Mnemonic for causes of weight loss.

If you memorize this for the test... god speed.
If you give supplements during a meal, will the elderly person get more or less calories than if the supplement is given an hour later?
Less calories.. Supplements are given as snacks between meals so that patients are not overfilled during a meal.
Orexigenic
stimulate appetite
Of the following which has msot evidence for appetite stimulation

Cyrpoheptadine, Progestational, Cannabinoids, Anabolic
Progestational (megastrol). Some evidence for cannabinoids (dronabinol)
When should anabolic steroids be used.
to treat sarcopenia... NOT anorexia
Patients with cytokine excess should not use:_______
Megestrol
For palliative care what is better? Magestrol or dronabinol?
Dronabinol
how do cytokines affect hunger?
Decreases hunger.
how do cytokines lead to frailty?
anorexia, confusion, sickness, osteopenia, decreased albumin, sarcopenia, loss of nitrogen, atherosclerosis, anemia
How do cytokines affect insulin.
It makes you insulin resistant.
Megestrol has what 4 side effects?
Hyperglycemia, Adrenal Suppression (supplement testosterone), Hypogonadism, Deep Vein Thrombosis
Is Megestrol Progestational or Canniboid?
Progestational
Is dronabinol Progestational or cannabinoid?
Cannabinoid
How long should Megestrol be administered?
No more than 3 months
Common: diarhea, nausea, vommiting, loose-watery stools, 3-5 days, sick contacts

Maybe: mild abdominal pain, fever

No: blood or mucus
Viral Gastroenteritis
Common: blood and mucus, abdominal cramping, fever, travel

No: nausea, vomiting
Bacterial Infection or Amebiasis
Common: abrupt onset, nausea, vomitting, 1-2 days

Maybe: light fever, abdominal cramping, family members affected

No: systemic illness, blood or mucus
Food Poisoning
Common: asian, african, native american populations, loose watery stools, gas, bloating, worse after lactose meals, resolve when lactose removed

No: blood, mucous, fever, weight loss, systemic symptoms,
Lactose Intolerance
Common: 10-30years old, northern european/ashkenazi jews, rectal bleeding and purulent secretions without diarhea, andominal cramping, fever

Maybe: constipation, blood and mucus (severe),
IBD: Ulcerative Colitus
Common: 10-30years old, northern european/ashkenazi jews, diarhea, blood, mucus, significant abdominal pain, fever,

Maybe: weight loss, arthritis, rash, uveitus
IBD: Crohn's disease
Common: crampy abdominal pain (worsened by fatty meals), altered pattern of bowel movements, exacerbated by stress or anxiety, constipation, low volume loose stools,

Maybe: mucus, bloating,

No: blood,
Irritable Bowel Syndrom
Common: loose watery stools, gas, bloating

Maybe: abdominal cramping, anorexia, weight loss, (camping, daycare, contaminate water link)

No: blood, mucus
Giardia infection
Common: first year of life, loose foul smelling stool, failure to thrive, coughing, wheezing
Cystic fibrosis
Common: Gluten sensitivity, bimodal onset (8-12 months or 30s and 40s) loose, foul smelling stools, failure to thrive, *dehydration*, weakness fatigue weight loss.
Celiac Sprue
What are the 5 pathophysical causes of diarhea?
1.) Osmotically active poorly absorbed solutes
2.) Active ion secretion
3.) Intestinal motility abnormality
4.) Mucosal morphology issues
5.) Pancreatic enzyme defects.
Sorbitol and magnesium will make you?
poop the loose stuff
What if you ate a lot of calcium?
you would poop less
Secretory diarhea is caused by what?
toxins or bacterial infection.
IBS causes diarhea by what mechanism?
Deranged intestinal movement.
CFTR is made where?
The pancreas
Aside from lactose in tolerance, what form of diarhea can (sometimes) be associated with lactase deficiency?
Viral gastroenteritus sometimes. leads to temporary lactase intolerance.
What is the age of onset for lactose intolerance?
8-10 years old.
in order to catch celiac sprue which has similar symptoms to cystic fibrosis, what should you ask about?
Dehydration - still producing tears when crying?
50% of americans diet annually? how many maintain significant weight loss?
5-10%
What is "significant weight loss"?
10% of body weight lasting 1 year.
Why do people love the atkins diet?
In the first four months, it is the msot effective diet... not so much after that.
What is the key feature of the ornish diet?
Low fat
What is the key feature of Atkins diet?
Low Carb
What is the Common Sense Diet?
-Whole grain, high fiber, filling carbs
-increased protein with emphasis on lean sources
-focus on complex nutrition not jsut the big 3 (fat,protein, carbs)
-no one diet works for all!
What percentage of carbs do you need per day?
45-65%
How much of your daily carbs should be fiber?
25-35g/day
Protein percentage of total calories?
10-35%
Fat percentage of total calories?
20-35%
how many carbs per gram

Carb? Fat? Protein?
4kcal/g = carbs
9kcal/g = fats
4kcal/g protein
how many calories = 1 pound of body weight?
3500 calories = 1pound
What are the minimum calories for men and women who are dieting?
1200 Women, 1500 men
There are 4 levels of vegetarian evil list them.
Semi Vegetarian (fake), LactoOvo, Lacto-, and vegan.
List the nutrients that are deficient in vegan diets.
Protein (meat), Calcium (milk), Zinc, Iron, Omega 3, B-12, Vitamin D (milk)
Protein Digestibility Corrected AMino Acid Score.
flawed. determines a relative protein content in vegetarian foods which can be absorbed?

honestly don't know or care what this is.
Cyclooxigenase... does what?
inititates production of eicosinoids. target of NSAIDS
Glucagon stimulates hormone sensitive lipase via what seondary messenger pathway?
CAMP --> PKA --> Hormone sensitive lipase
What converts PIP2 to IP3 and DAG?
Phospholipase C
Phospholipase C does what to PIP2 what is the purpose?
forms DAG and IP3 whih are both neccesary to activate calcium dependent protein kinase C.
In the PI cycle, what happens to diacylglycerol?
It is recycled via phosphorylation to form phosphatidic acid which is a precurso for phosphatidyl inositol which can be phosphorylated twice to PIP2 (cycle!)
Overstimulation of PKC can lead to waht>
Cancer
Describe the two ways to release arachidonic acid from glycerophospholipids.
1.) Phospholipase A2

2.) Phospholipase C releases diacyl glycerol and then diacylglycerol lipase releases one FA and monoacyl glycerol lipase releases the other.
Why do we need linoleic acid?
It elongates fatty acids so we can have double bonds past the 10th carbon.
Cyclooxigenase has two enzymatic components... __ and ___
Oxigenase and peroxidase
PGH2 can be made into thromboxane A2 or remain as itself... called?
Prostacyclin
Why does ibuprofin and aspirin cause gastric bleeding?
because it blocks Cox 1 which is essential in gastric secretion.
why was Cox II thought to be the bad Cox? Why shouldn't you block it?
It controls inflammation - it is also important, hoever, in coronary blood flow... so dont block it too well.
Which of the following isn't an NSAID?

Aspirin, Hank Zhang, Acetominophen, Ibuprofen, Celebrex
Hank and Acetominophen
Aspirin and Ibuprofen COX block by two different mechanisms. explain.
aspirin is a covalent inhibitor while ibuprofen is a competitive inhibitor of arachidonic acid binding.
Celebrex and Vioxx block what version of Cox specifically? What side effects should you consider when prescribing it?
Cox-II - possible errors in coronary blood flow.
Low dose aspirin does what?
prevents cardiovascular disease by preventing platelets form making thromboxane A2 and leading to platelet aggregation/ vasoconstriction.
PGI2 PGE2 PGD2 do what?
Vasodilation and platelet aggregation
PGF2 does what?
Vasoconstriction, bronchoconstriction, smooth muscle contraction.

D,E and I, say Why the F is PGF constricting everything.
Leukotrienes do what?
Anyphalaxis
Vascular permeability, T cell proliferation, Leukocyte aggregation,
LTB4 does what?
Increase vascular permeability, T cell proliferation, Leukocyte aggregation, INF-gamma, IL-1, IL-2

Anaphylaxis!
LTC4 and LTD4 do what>
Bronchoconstriction, Vascular permeability, INF-gamma

Anaphylaxis!
List three sources for amino acids in the AA pool:
Diet, Body sources, Synthesis
The small intestine absorbs amino acids in what form(s)?
Dipeptides, and free amino acids.
How does amino acid malnution occur with cystic fibrosis?
Gallbladder function is affected, so digestive enzymes are a hindered.
Celiac sprue affects what histological component?
Microvilli in the small intestine.
Edema is a common result of a shortage of what protein?
Albumin (hypoalbuminia)
By what mechanism are amino acids transfered into the portal vein??
Secondary active transport followed by facilitated diffusion.

Na/ATP ase pumps Na into the intestinal lumen. Co transport occurs with AAs and sodium. AAs pass into the portal vein via facilitated diffusion.
What is the primarty pathology of cysteinuria?
Kidney Stones
Hartnup Disease
inability to transport branched and aromatic amino acids. Leads to pellagra.
What is the major site of protein turnover for palsma proteins?
Liver
What are the two pathways of protein degradation discussed in class?
Lysosomal and Ubiquitin
The proteosome is a key component of lysosomal or uqbiquitin based protein degradation?
Ubiquitin
Angelman syndrome and Von Hippel-Lindau Syndrome result from a defect in what protein degradation pathway?
Ubiquitin
Characterized by developmental delay, lack of speech, ataxia, very happy expressive demeanor - results from defects in the ubiquitination pathway.
Angelman Syndrome
This ubiquitinization pathway defect leads to a predisposition to tumors.
Von Hippel-Lindau Syndrome.
Tay Sachs Disease
defect in hexosaminidase A which degrades GM2 gangliosides. Leads to neurodegeneration

Lysosomal degradation disease
Sly syndrome is a defect in what protein degradation pathway?
Lysosomal
Altzheimers, huntingtons, parkinsons disease are at least partially caused by what?
Proteinopathies due to misfolded proteins.
Ornithine transcarbamoylase deficiency
Orotic acid is produced when the urea cycle is overloaded. Leads to ammonia poisoning. It is an X-linked genetic disease. Some girls live as mosaics, the abnormal cells overwhelm the normal cells later.
Why is ammonium toxic?
Positive charge with simliar size and shape to potassium Blocks channels.
how does ammonia act as a neurotoxin?
It blocks potassium channels.
Trans aminase reactiosn tranfer amino groups to what group?
Alpha keto acid groups.
Acetominophen is toxic to the liver during overdose why?
NAPQI can degrade proteins and nucleic acids releasing NH3
List the enzymes of the urea cycle.
1.) Carbamoyl phosphate synthase 1 (CPS1)

2.) Ornithine transcarbamoylase (OTC)

3.) Arginosuccinate synthetase

4.) Arginosuccinate lyase

5.) Arginase
List the intermediates of the urea cycle
1.) Bicarbonate + NH4 + ATP =CPS1= Carbomyl Phosphate

2.) Ornithine + Carbamoyl Phosphate = OTC = Citrulline

3.) Citrulline + Aspartate + ATP = ASS = Arginosuccinate

4.) Arginosuccinate = ASL = Arginine + fumarate

5.) Arginine = Arginase = Urea + Ornithine
What urea cycle intermediates can transport out of the mitochondria?
Ornithine and citrulline.
Aspartate feeds into the urea cycle by what amino acid?
Glutamate
High levels of arginine stimulates the urea cycle by what mechanism?
It promotes the formation of N-acetyl-glutamate from glutmate and acetyl coA which in turn promotes CPS1.
Carbamoyl Phosphate overload leads to to what accumulation?
Orotic Acid.

Later High ammonia.
How does ammonia overdose make you sleepy?
It blocks potassium channels.
If carbamoyl phosphate accumulates to high levels, what enzyme is likely affected?
OTC - ornithing transcarbamoylase
Of the 5 urea cycle enzymes, which are mitochondrial and which are cytosolic?
CPS1, OTC = mito

ASS, ASL, Arginase = Cytosolic
If you have...

LEthargy, Vomitting, Ataxia, Seizures, Coma, Death and excretion of urea cycle intermediates you may have?
Hyperammonemia.
If carbamoyl phosphate accumulates to high levels, what enzyme is likely affected?
OTC - ornithing transcarbamoylase
Of the 5 urea cycle enzymes, which are mitochondrial and which are cytosolic?
CPS1, OTC = mito

ASS, ASL, Arginase = Cytosolic
If you have...

LEthargy, Vomitting, Ataxia, Seizures, Coma, Death and excretion of urea cycle intermediates you may have?
Hyperammonemia.
hypericum is an herbal medication also known as?
St. john's Wort.
What are the 3 key reasons people look for herbal remedies (SPINNING SLIDE!)
1.) Cold/Flu
2.) Joint Health
3.) Heart Health
What are the 3 key reasons people look for herbal remedies (SPINNING SLIDE!)
1.) Cold/Flu
2.) Joint Health
3.) Heart Health
What are the 3 key reasons people look for herbal remedies (SPINNING SLIDE!)
1.) Cold/Flu
2.) Joint Health
3.) Heart Health
What are the 3 key reasons people look for herbal remedies (SPINNING SLIDE!)
1.) Cold/Flu
2.) Joint Health
3.) Heart Health
Dietary Supplements are defined as_____ by the FDA. What does this mean?

SPINNING SLIDE!!!!
Food - This means that they are not regulated by the FDA!!!!!

German and Japanese Supplements are regulated
What is Echinacea used for?
Colds/Flu - boosts immune response.
St. Johns Wort is used for.
antidepressant
What is a side effect of St. Johns Wort?
induces cytochrome p450 - effects drug metabolism.
Ginkgo does what?
Memmory support, treats mountain sickness.
Valerian does what? Side effect?
Calmative herb - tranquilizer/sleep aid.

Activates p450
Arginine is an essential amino acid when?
Growth or injury
3 carbon Amino Acids come from what two preddcursors?
Pyruvate (alanine) and Phosphoglycerate (Glycine, Serine, Cysteine)
4 carbon aminoacids come from what precursor?
Oxaloacetate via a transamination
What nonessential amino acid is not synthesized in some cancer cells
Asparagine
5 carbon amino acids come from what precursor?
alpha-ketoglutarate.
What does phenylalanine hydroxylase do? What do you get when it is deficient? What cofactor does it require?
Converts phenylalanine to tyrosine.

Defect = PKU or hyperphenylalanemia

BH4
Two issues lead to PKU what are they?
Phenylalanine hydroxylase deficiency

BH4 deficiency
Degraded amino acids are categorized into two groups what are they?
Glucogenic = TCA cycle + Gluconeogenesis

KetoGenic = makes ketone bodies (Acetoacetate etc - used in brain)
Methionine degradation requires what amino acid?
Vitamin B12
Cystathionine b-synthase deficiency causes what
homocysteinuria
What are the symptoms of alcapturia?
black urine and arthritus. cused by homogentisate oxidase defects in the degradation of Phe and tyrosine.
Maple syrup urine disease is an issue involving breakdown of what type of amino acid?
Branched chain AAs
What enzyme is defunct in Maple Syrup urine disease
BCKAD

Branched chain ketoacid dehydrogenase
tryptophan degradation is key for what electron carrier?
NAD and NADP (it contains the nicotinomide moiety)
How much niacin is synthesized in our body? where is it from?
50% of our need = tryptophan
Pellagra is a deficiency of what?
Vitamin B3 (Niacin)

could be caused by tryptophan deficiency.
Catecholamines are synthesized from what essential amino acid/
Phenylalanine --> Tyrosine --> catecholamines.
What converts norepinephrine to epinephrine?
SAM
What is deficient in parkinsons disease?
Dopamine producing cells = dopamine
What amino acid is a precursor for melanin?
Tyrosine
How does PKU lead to fairer appearance?
low levels of tyrosine leads to less melanin production.
Albinism is a defect in what enzyme?
Tyrosinase
Succinyl CoA and what amino acid are essential for Heme synthesis?
Glycine
Lead blocks what two reactions in heme synthesis?
ALA dehydratase and Ferrochetalase
Lead is bad because it blocks synthesis of what?
Heme
An anemic kid from a poor neighborhood should has his home checked for what?
Lead poisoning
Porphyria is a disease of what?
Heme synthesis (porphyrins)
List the intermediates in heme breakdown
Heme --> Billiverdin --> Billirubin (insoluble)
How does billirubin reach the liver if it is insoluble?
it is conjugated to albumin.
What is elevated in jaundice?
Billirubin
what are 4 causes of jaundice?
1.) hemolysis
2.) Liver damage
3.) Glucuronyl transferase deficiency
4.) bile duct obstruction
G6PD deficiency leads to jaundice how?
reduces resistance to oxidative stress (leads to hemoltic anemia)
Ribose 5-phosphate is a key component of nucleotides. How do purines and pyrimidines differ in their incorporation of ribose 5 phosphate?
Purines begin with robose while pyrimidines build the base first and then add ribose.
Differentiate between base nucleoside and nucleotide
Base = base
Base + Sugar = nucleoside
Base + Sugar + Phophates = nucleotide
what is hypoxanthine?
forms from spontaneous deamination of adenine. binds with uracil.
What is the first committed step of purine synthesis?
transamination of glutamine to form 5-phosphoribosamine.

Glutamate PRPP amidotransferase
In purine synthesis, Glutamate PRPP amidotransferace exchanges an amino group from glutamine to waht group on PRPP?
the PPi moiety.
What amino acid's contribute to purine synthesis?
QGQD - glutamine, glycine, glutamine, Aspartate


Also FOLATE!
Glutamine PRPP amidotransferase in regulated by what 4 things?

How chemically does this occur?
AMP, GMP, IMP, (negative) and PRPP (positive)

The negative regulators push toward the inactive dimer state while PRPP promotes the active monomer
where are nucleotides synthesized de novo?
Liver
What enzymes salvage purine bases?
Hypoxanthine-Guanine Phosphoribosyl transferase (HGPRT) salvages IMP and GMP

Adenine phosphoribosyltransferase salvages AMP
Purine salvage affects purine synthesis via what mechanism.
The PRTs (HGPRT and APRT) consume PRPP which is a promoter of purine synthesis.
all purines are degraded through what intermediate?
Xanthine --> Uric Acid via xanthine oxidase.
SCID is a deficiency of what enzyme... what is the problem?
Adenosine deaminase is defunct... this causes inability to produce t and b cells.
Rod shaped crystals in gout is what?
Uric Acid crystals. (Sodium Urate)
how do you treat acute gout? (2 drugs)
Colchicine (been around for 100s of years... now is FDA approved = $$$)

Allopurinol - inhibits xanthine oxidase
Uricase does what? What are the hazards
Converts uric acid to allotonin (more soluble

Does not exsit in humans so youneed anymal form PEG-uricase (immune response)
Lesch-Nyan syndrome is a defect in what enzyme?
HGPRT in hypoxanthine and guanine degradation
how does Von Gierke's disease cause gout.
Glucose-6-phospatase deficiency shunts the Pentose phosphate pathway toward nucleotide synthesis... leads to nucelotide degradation increase... therefore uric acid and gout.
What is the regulated step in pyrimidine synthesis?
Carbamoyl phosphate synthetase II - it is deactivated by pyrimidines and activated by PRPP
Hereditary orotic aciduria is a defect of what enzyme.
UMP synthase in the pyrimidine synthesis pathway. Leads to orotate buildup.
What amino acids are essential for pyrimidines?
Glutamine and Aspartate
What is hydroxyurea?
An antiviral drug which blocks the formation of Deoxynucleotides by Ribonucleotide reductase
What converts RNA to DNA
Ribonucleotide reductase
UMP is formed from what other nucleotide di phosphate?
CDP
formation of TMP is done using what cofactor?
Tetrahydrofolate in thymidilate synthase
What regenerates tetrahydrofolate for use in TMP formation?
Dihydrofolate reductase (DHFR)
What does methotrexate do>
Inhibits Dihydrofolate reductase. Prevents regeneration of tetrahydrofolate. (less TMP = less DNA) Treats leukemia!

ITS MUSTARD GAS!!!
Methotrexate, 6-mercaptopurine, and vincristine are similar to what?
MUSTARD GAS! - blocks dihydrofolate reductse which is neccesary for TMP formation.

causes T and B cell deficiency - key for leukemia treatment.
Bilateral dilocated lenses, Glaucoma, malor flush, mental retardation, osteoporosis, compression of vertebrae, cardiovascular disease
Homocysteinuria
How do you treat homocytinurea nutritionally?
Protein restrictive diet.
what enzyme converts homocysteine to methionine? What cofactors does it require?
Methionine synthase - needs VitB12 and folate
What enzyme converts homocysteine to cystathionine? (in order to form cystein) What cofactor does it need?
Cystathionine b-synthase

Pyridoxine phosphate
What drug therapy can bypass methionine synthase?
Betaine
B12 and Folate deficiency leads to what in RBCs (and all cells)
MAcrocytosis
The Amino acid stress test for vitamin deficiencies consists of what 3 AAs?
Methionine, Tryptophan, and Isoleucine.
Why does folate deficiency lead to so many pathologies?
it is involved in the formation of SAM which methylates many targets in many body systems.
FIGLU and mathylmalonic acid excretion indicates what?
Folate Trap due to Vitamin B12 deficiency
Explain the folate trap.
Folate must be reduced to tetrahydrofolate to function. In order to be replenished, you need vitamin b12... in b12 deficiency, you trap this folate.
How does folate deficiency, or the folate trap lead to macrocytosis?
you need folate to form thymine... Without thymine, you cannot have cell division... so your cells jsut grow but never divide.
What is the most common cause of methylmalonic acidemia?
Short gut syndrome.
Sulfa drugs act on what portion of folate?
Para amino benzoic acid.

They replace it with the sulfa ring and rprevent folate synthesis.
What leads to hypersegmentation in folate deficiency?
fewer histones.
What is trapped in folate trap?
N5-Methyl FH4
Epinephrine, Creatine, Metylated nucleotides, phosphatidylcholine, and melatonin have what in common?
they all require methylation by SAM in their synthesis.

SAM is dependent on vitamin B12 and folate
Spina Bifida is caused by what in folate deficiency?
Macrocytic neurons
5 -flourouracil does what to treat skin cancer?
blocks conversion of udp to Tdp. no division.. no cancfer spread.