AN II exam 1
Thiamin, vitamin ______ has both coenzyme and non-coenzyme roles
The ___________________ role of thiamin is used for: 1) metabolism of _____________________ and ____________s
2) synthesis of __________________ for production of nucleic acid synthesis (deoxyribose for DNA and ribose for RNA) and ___________ (essential for fatty acid synthesis)
coenzyme, carbohydrates, BCAAs, pentoses, NADPH
The _____________________ role of thiamin is used for: ____________________ and ____________ conduction
non-coenzyme, membrane, nerve
The major role of TPD (thiamin) is in the pyruvate dehydrogenase complex for __________________ ________________________
= removal of a carboxyl group (-COOH) from pyruvate releasing it as carbon dioxide (CO2) so acetyl coA can be made
what are the specific enzyme complexes that use thiamin (in its coenzyme role)? 4 complexes
1) pyruvate dehydrogenase complex (pyruvate -> acetyl coA)
2) alpha-ketogluterate dehydrogenase complex (converts alpha-ketogluterate -> succinyl coA within TCA cycle)
3) branched-chain alpha-keto acid dehydrogenase (BCKAD) complex (combination of enzymes responsible for degradation of
4) pentose phosphate pathway (TDP, thiamin, works as prothetic group of transketolase, which is needed for NADPH and pentoses)
What are the signs of thiamin deficiency?
"beri" means weakness; muscle wasting, nerve damage
this type of beriberi occurs primarily in adults with low chronic thiamin intake and high carbohydrate intake; muscle weakness and wasting occurs, especially in lower extremities
this type of beriberi has more extensive cardiovascular involvement compared to dry beriberi - rapid heart beat; cardiomegaly (enlarged heart); edema (swelling, "pitting" edema); edema and heart disease/issues stem from heart not pumping as well as normal and fluid builds up
this type of beriberi occurs primarily in infants from a nursing mother suffering from beriberi; symptoms include anorexia, vomiting and lactic acidosis occurs b/c thiamin is needed to convert pyruvate to acetyl coA so instead pyruvate is converted to lactic acid
Why does a high carbohydrate diet aggravate a thiamin deficiency?
it is especially a problem with dry beriberi b/c you cannot utilize pyruvate and convert it to acetyl coA when you do not consume enough thiamin; most of the acetyl coA would not come from carbs, but come from protein, thus causing muscle wasting; decreasing carbs and increasing protein and fats would help with providing enough acetyl coA
thiamin deficiency in alcoholics can cause this; causes paralysis of ocular muscles (opthalmoplegia), constant, involuntary eyeball movement (nystagmus), and impaired muscle coordination (ataxia)
Riboflavin is vitamin ______; "flavus" means _____________ in Latin
FAD and NAD are similar in structure and makeup; the only thing that changes is the vitamin, either _____________ or _____________________
niacin or riboflavin
__________ acids enhance B2 absorption
(B2 is involved in fat usage; so how much lipid is in the diet will affect riboflavin absorption; ex: if you drink a glass of skim milk, fat is not digested as well)
what is the major coenzyme form of riboflavin? what is the other coenzyme form?
How does riboflavin (B2) relate to metabolism of vitamin B6?
pyridoxine phosphate oxidase converts PMP and PNP to pyridoxal phosphate (PLP), the primary coenzyme form of vit B6
pyridoxine phosphate oxidase activates B6 to its main coenzyme form (PLP) through dependence on ________________ for activation
_________ is involved in all metabolisms of the three macronutrients (carbs, fat, protein)
you can make ____________ (B1) from tryptophan and riboflavin (B2) is required for this process
How is riboflavin related to anabolism of iron?
riboflavin is required for the synthesis of B6 which makes PLP (the active form of B6), which is required for heme (iron) production; thus, without riboflavin, B6 cannot be made, and then heme iron cannot be made
what are the signs and symptoms of riboflavin deficiency (ariboflavinosis)?
- cheilosis (painful lesions on outside of lips and corners of mouth; aka angular stomatitis)
- glossitis (inflammation of the tongue)
- seborrheic dermatitis (associated with waxy substance found noticeably around nose)
- bloody, red and swollen oral cavity
how can phototherapy for babies with jaundice affect B2?
phototherapy converts bilirubin to compounds that can be excreted via fecal and urine routes, but the phototherapy causes riboflavin destruction because thiamin (B2) is liable in light
niacin circulates in blood as __________________ b/c nicotinic acid would affect pH of blood; also, this form of niacin is the primary precursor of NAD, which is made in all cells
What are the differences in structure between nicotinic acid and nicotinamide?
nicotinic acid - has carboxyl group/carboxylic acid (COOH)
nicotinamide - has amino group (CONH2)
______________________ enzymes usually require NAD/NADH; this enzyme is an enzyme that catalyzes the transfer of hydrogen or electrons from a donor (oxidizing it), to an acceptor (reducing it)
NAD= nicotinamide dinucleotide
NADP= nicotinamide dinucleotide phosphate
when _______________ is used as a combination treatment, lipid-lowering drugs are not needed in as high of doses
nicotinic acid can be prescribed at large doses to treat ______________________ (up to 6/day)
1) one mechanism of action for pharmacological doses of niacin to reduce lipids is: inhibition of _________________ in adipose tissue
2) another mechanism of action for pharmacological doses of niacin to reduce lipids is: decreased __________ synthesis, and thus decreased _________ production
3) another mechanism of action for pharmacological doses of niacin to reduce lipids is: inhibition of diacylglycerol _______________________
4) another mechanism of action for pharmacological doses of niacin to reduce lipids is: increase in _________ levels
note that niacin is not really used anymore b/c __________ are so much more effective now and safer than they used to be
niacin in large amounts can result in vasodilatory effects- flushing (burning, tingling, itching sensations accompanied by red flush on face, arms, and chest); GI symptoms; liver injury; hyperuricemia or gout; glucose intolerance; blurred vision
one of the consequences of niacin deficiency is _______________, meaning "rough skin"
- the 4 D's result from pellagra are: dermatitis, dementia, diarrhea, death
do not forget, B6 is needed for conversion of tryptophan to niacin, but the conversion is not very efficient; only about ____% of tryptophan in the diet gets converted to niacin - very tiny amount
biotin is found in many foods: beef, soybeans, egg yolk, cereals, nuts; also made by _______________ in large intestine
___________ in raw egg whites binds to biotin, thus blocking its absorption, but this compound is heat liable so it gets destroyed in when cooked
this biotin-dependent carboxylase converts pyruvate into oxaloacetate; it replenishes oxaloacetate for TCA cycle/gluconeogenesis
this biotin-dependent carboxylase makes malonyl coA from acetyl coA; it commits acetyl coA to fatty acid synthesis
acetyl coA carboxylase
this biotin-dependent carboxylase converts propionyl coA into methylmalonyl coA; important in metabolism of amino acids and odd numbered FAs
propionyl coA carboxylase
this biotin-dependent carboxylase converts B-methylcrotonyl coA in B-methylglutaconyl coA; important in catabolism of leucine and isoprenoid compounds
B-methylcrotonyl coA carboxylase
1) one non-coenzyme role of biotin is the __________________ of proteins (histones)
(adds biotin to the protein group)
2) another non-coenzyme role of biotin is to stimulate the expression of ____________________
(glucokinase enzyme either phosphorylates or dephosphorylates -add/removes phosphorous- glucose molecules)
3) another non-coenzyme role of biotin is to inhibit expression of phosphoenolpyruvate _________________
4) another non-coenzyme role of biotin is that it is important for normal progression of the _________ ____________
what is this?
- the structure of biotin
what is this showing?
how biotin attaches to a carboxylase through an amide linkage to form a biotinylated carboxylase
in pantothenic acid, "pantos" means ___________________ in Greek b/c anything that has a coA attached to the name means that it contains pantothenic acid
What are the two primary cofactor forms of pantothenic acid?
coA and 4-phosphopantetheine
coA binds to __________ groups via a thio (sulfur) ester bond with carboxylic acid and transfers the __________(same as blank above) groups as needed
ex: the carboxylic acid of acetyl coA is ___________ __________, to which then the coA gets attached
malocnic acid becomes ____________ _________, propionic acid becomes _____________ __________, and succinc acid becomes _____________ __________
the prosthetic group for acyl carrier protein (ACP) is required in what process?
the sulfhydryl group in 4'-phosphopantetheine binds and transfers ___________ groups to another sulfhydryl group located in the enzyme complex
ex: first, malonyl coA binds binds to 4-P-pathetheine and on a second step, it is transferred to the enzyme complex via _________
-this is why pantothenic acid is so important for fat metabolism
____________________ refers to donation of long-chain fatty acids or acetate to proteins
________________: shorter chains of carbons
________________: can be longer chains of carbons
What is the most common form of pantothenic acid in the body?
coenzyme A (coA)
what is the major form of vit B6 in the body?
B6 has everything to do with ________________ metabolism
Which enzymes require vit B6 as a cofactor and what are their functions?
more than 100 coenzymes require B6
this role of the vitamin that is thought to account for the use of more than 50% of body’s vitamin B6 (most common role in muscle)
most of the B6 found in muscle is present as PLP, which in turn is bound to glycogen phosphorylase
vitamin B6 is absolutely necessary for heme synthesis because it is a cofactor for ______________ synthase; without this enzyme, heme cannot be made
without enough B6, RBCs become small and contain low levels of ________________________, which is necessary for oxygen transport throughout the body
_____________ ______ and glycerin are the beginning of heme. B6 is necessary for heme formation, and with a deficiency, anemia can occur
(heme is what gives the cell its bright color because t is carry oxygen for/in the blood)
1) this coenzyme role of B6 plays in the transfer of an amino group (-NH2) from one amino acid to an alpha keto acid and is an important reaction for the synthesis of nonessential amino acids and for the use of amino acid carbon skeletons for energy or glucose production:
the two most common amino transferases for which PLP or PMP (B6) is coenzyme for are:
GOT (glutamate oxaloacetate transferase; aka aspartic amino transferase, AST) - this aminotransferase found in higher concentration in the heart
GPT (glutamate pyruvate transaminase; aka alanine aminotransferase, ALT) - this aminotransferase found in higher concentration in the liver
PLP (B6) is especially important in muscle so that muscle can convert glutamate to glutamine and alanine to pyruvate (remember muscle will not give up _______________, only AA)
PLP is also involved in ______________________, the removal of an amino group
2) this coenzyme role of B6 plays in the removal of the carboxyl (COO-) group from an amino acid or other compound; neurotransmitter synthesis (ex, production of serotonin):
3) this coenzyme role of B6 plays in the irreversible break down of homocysteine to cysteine; the reactions in this process require two PLP enzymes:
related to transulfhydration, if you have a deficiency in B6, what will there be a rise in?
4) this coenzyme role of B6 plays in the reaction in which an amino group is removed from a compound such as an amino acid and released as ammonia or ammonium ion:
5) this coenzyme role of B6 plays in the removal of a hydroxymethyl group from serine:
the purpose of iodine is really to make ______________ hormones
for the synthesis of the thyroid hormone T4 (thyroxine), how many iodide atoms are needed?
for the synthesis of the thyroid hormone T3 (triiodothyronine), how many iodide atoms are needed?
this is the hormone that regulates thyroid hormone synthesis and secretion
TSH (thyroid stimulating hormone)
secreted from pituitary, then sends signal to thyroid to produce more T3 or T4
the thyroid makes more T4 than T3
true! (50-100x's more)
how are thyroid hormones formed?
step 1) iodide is ______________ transported into the cell
how are thyroid hormones formed?
step 2) iodide gets attached to a _______________________ and forms Thg-MIT
how are thyroid hormones formed?
step 3/4) Thg-MIT is iodinated to form Thg-DIT, which condenses with another Thg-DIT in the colloid to form _____________
how are thyroid hormones formed?
step 5) Thg-DIT also can condense with ____________ to form Thg-T3 and reverse (r)T3
how are thyroid hormones formed?
step 6) T4 and T3, now active thyroid hormones, are released into the blood following ______________________ of Thg-T3 and Thg-T4 back into the thyroid cell and hydrolysis of the Thg by proteases
(engulfing the whole thing)
thyroid hormones play a vital role in expending energy. what does this mean?
_______ is the most biologically active thyroid hormone
the function of thyroid hormone is mediated through effects in the ______________ of cells
thyroid hormones bind to __________ or interact with it via zinc fingers to increase mRNA expression and _______________ synthesis to:
- stimulate _____________ consumption
- increase __________ ________________ __________
- increase body __________ production
basal metabolic rate (BMR)
in adipose tissue, thyroid hormones do what?
in muscles, thyroid hormones do what?
in the bone, thyroid hormones do what?
promote anabolism (growth and development)
(anabolism expends energy)
in the cardiovascular system thyroid hormone does what?
increases heart rate
in the gastrointestinal tract, thyroid hormone does what?
stimulates nutrient digestion and absorption
for metabolism, thyroid hormone does what?
stimulates metabolic rate and cellular oxygen consumption in metabolically active tissue
this vitamin has the second highest intracellular concentration
(the first is K)
magnesium is protein-bound primary to this protein: _______________
magnesium is mostly found associated with ____________
magnesium is associated with phosphorus and calcium to form the ________________ ________________ during bone formation
magnesium is also important on the ________________ of bone; it is thought to contribute to an exchangeable pool to maintain blood levels
magnesium is also found in _____________________ fluids, primarily skeletal muscle
magnesium is bound to ______________________ in cell membranes for stabilization
* Mg allows smooth and and cardiac muscle ______________________ (Ca ions exchange)
- ratio affects muscle contraction
Mg is associated with DNA and proteins how? (2 ways)
nucleic acid synthesis
Mg is also a cofactor in over ________ enzyme reactions, two of which are:
* Mg is also associated with ATP in which pathways? (4)
glycolysis, TCA, HMP shunt, beta-oxidation
Mg is part of the tyrosine kinase activity at the ______________ receptor
the major form of choline in foods is as the ______________________ ______________
Choline is primarily found in the body in the form of ________________
in the brain, kidneys, and liver, lecithin gets cleaved by phospholipase C yielding a __________________ and _________________________
alkaline phosphatase cleaves the phosphate yielding free ______________
how does choline help decrease homocysteine levels?
free choline can be oxidized to betaine which serves as a methyl donor to homocysteine to generate methionine
which two enzymes work in oxidizing betaine?
betaine aldehyde dehydrogenase
free choline also has 2 other functions:
remember, choline can be synthesized in the body by methylation of _______________ by SAM
what does the K in vitamin K mean?
vit K is one of the few vitamins that is more bio-available in plant sources than animal
since vitamin K is a fat-soluble vitamin, where do you think most of our vit K is found?
what is the primary function of vitamin K?
blood clotting cascade!
all glutamic acid residues must be carboxylated for the protein to function. which K-dependent protein does this?
vitamin K really just allows _____________ to be able to attach to proteins to be used for bone mineralization and blood clotting
_____________________________ residues on major proteins for the blood clotting cascade; includes prothrombin (factor II), factor VII, IX, and X-formation of fibrin clot
calcium in needed for the blood clot; vit K allows for the ________-________ to form, so then calcium can "fit" in this and be utilized
1) in the vitamin K cycle, vitamin K is first present in blood in its ________________ form (vit K quinone)
2) in the vit K cycle, vitamin K quinone (oxidized) must be reduced by _________________ __________________ to work in carboxylation (dihydroquinone, KH2)
3) in the vit K cycle, ______________________ of proteins leads to formation of vitamin K 2,3-epoxide
4) in the vit K cycle, vitamin K quinone is reformed by ________________ _________________
the whole purpose of the vitamin K cycle is so that other proteins involved in blood clotting and bone mineralization can be _______________________
what is the mechanism of action of warfarin?
warfarin affects all of the vit K-dependent clotting factors
this means that warfarin inhibits blood clots (it is an anticoagulant); useful for decreasing death for those who are at risk for recurrent myocardial infarction, thromboembolic events (stroke, systemic embolization), or artificial heart valve replacement
folate must have all three of these parts to be folate
3) glutamic acid (can be more than 1)
-aka THF when it is reduced
what are the different cofactors of folate and what are their functions?
B12 - needed so the methyl from 5-methyl THF can donate its methyl to cobalamin (B12) to make methylcobalamin, which is the methyl donator to Hcy (homocysteine)
what are the different cofactors of folate and what are their functions?
riboflavin (B2) - cofactor for methylene THF reductase (accepts reducing equivalents from NADPH)
what is the methyl folate trap?
the methyl-folate trap is when there is not enough B12 to keep regenerating THF in the cells; essentially, the "trap" occurs when there is not enough cobalamin (B12) to take the methyls off of the 5-methyl THFs , and thus a buildup of 5-methyl THF occurs and cannot be converted to THF
how can an excess of folic acid mask a vitamin B12 deficiency?
excess folate/folic acid can mask a vitamin B12 deficiency by correcting megaloblastic macrocytic anemia, but neurological damage form lack of B12 still occurs and is irreversible; when there are large amounts of folate in the diet, the body does not need B12 to regenerate THF; thus, the high folate consumption can still produce DNA and correct macrocytic anemia, but there is still that B12 deficiency being masked
what is the role of the enzyme methylene tetrahydrofolate (THF) reductase (MTHFR)?
converts 5,10 methylene to 5 methyl THF, which requires FAD
this enzyme is necessary for remethylation of Hcy
what would happen if there were a defect in MTHFR?
high homocysteine!; cannot methylate homocysteine to methionine
what does methotrexate do?
inhibits dihydrofolate reductase (DHFR) which keeps DNA from being divided; thus, methotrexate inhibits the whole step of utilizing THF
related to the article about folate, what types of supplements would be indicated for patients taking methotrexate and why?
5-MTHF would be a good supplement because
1) the DHFR-catalyzed reaction would reach saturation easily (this run allows DNA to be divided) and
2) 5-MTHF does not mask a vitamin B12 deficiency like folic acid supplements might
what kind of anemia can result from a folate deficiency?
megaloblastic macrocytic anemia
(megaloblastic = odd oval shape with distorted nuclei; macrocytic = large; high mean cell volume (MCV))
* cells divide later, and when that happens they have more time to become larger (so what you see is a macrocytic -large- RBCs); these larger cells are a key clue to folate or B12 deficiency; this is for CELL DIVISION (not color - that’s heme)
why is B12 called methylcobalamin?
the Co (cobalamin) in the middle of the molecule
what changes in the different forms of B12?
synthetic B12 in fortified foods in fortified foods is not bound to _________________
digestion: naturally occurring B12 in food is bound to ________________, and must be released from this for absorption
_______________ acid (HCl) is essential for breaking B12 off of protein
absorption: ______________ helps with HCl to break down the protein to release the B12, then it is attached to another protein called "______" protein
in the duodenum, R protein is hydrolyzed and free _________________ results
cobalamin binds to ________________ factor (IF) after release from R protein thus forming IF-B12 complex
______________ complex traverses entire length of small intestine
in the ilium, IF-B12 is absorbed via binding with receptors known as ________________
(these are the proteins that cabolamin binds to once in the ileum)
finally, ________________ ________________ occurs equally throughout GI
only about 1-2% of oral dose is absorbed of cobalamin
this is a picture of cobalamin digestion/absorption
how does vitamin B12 work with folate?
vitamin B12 accepts the methyl group from 5-methyl THF
what is the role of the enterohepatic circulation in maintaining vitamin B12 status?
B12 gets reabsorbed with bile; so B12 can be secreted with bile and then be re-absorbed again
-this is the reason that a B12 deficiency develops more rapidly in individuals who malabsorb (pernicious anemia) vs those who consume vegetarian diet
What kind of anemia can result from a B12 deficiency?
pernicious anemia - caused by lack of functional IF in stomach; can't absorb B12 b/c do not have intrinsic factor (autoimmune destruction of gastric parietal cells)
another anemia resulting from B12 deficiency
megaloblastic macrocytic anemia
- when not enough B12 to accept methyl from 5-methyl THF, causes RBCs to divide later, which allows RBCs to have more time to become larger in size, resulting in the above anemia
which enzymes require zinc (Zn) as a cofactor?
component of metalloenzymes
includes carbonic anhydrase, alcohol dehydrogenase (alcohols to aldehydes, ex: retinol-> retinal), carboxypeptidases (protein digestion), superoxide dismutase (free radical terminator)
how does zinc affect gene expression?
zinc fingers stabilize the folds in genes
what is the function of chromium (Cr)?
potentiation of the action of insulin via chromodulin
____________________ is produced in response to insulin secretion which stimulates Cr uptake by beta cells
chromodulin binds to the cytosolic beta subunits of the insulin receptor and stimulates ____________ activity
chromium is mostly bound to ___________________, but if transferrin is not available because of binding to iron, it may bind to other proteins
what are the enzymes that require iron as a cofactor?
this iron protein absorbs intact heme in the duodenum
this iron protein is the transporter for ferrous iron; located everywhere in the body
synthesis of DMT1 is affected by iron status (increased synthesis with low status, decreased expression with increased enterocyte iron concentration)
this iron protein transports iron to the basalateral membrane and out of the intestinal cell
this iron protein oxidizes ferrous iron to ferric iron when transport out of intestinal cells occurs
this iron protein is critical for iron transport by transferrin (transferrin transfers oxidized state of iron); works as an antioxidant to eliminate free radicals produced by phagocytosis of invading organisms by WBCs; also called acute phase protein b/c its concentration increases in blood during inflammatory response; 6 copper atoms get attached to this protein (it is the primary form of circulating Cu, 60-70%); this protein delivers Cu to tissues after binding to specific membrane receptors
transports the ferric iron (oxidized iron) that was converted by hepaestin; most of the iron transported by this enzyme comes from degradation of hemoglobin
this is an iron storage protein, specifically stores broken-down iron; predominates over ferritin under high iron concentrations
this iron protein binds up to 3 iron atoms in the intestinal cell so that the iron is prevented from oxidative damage; chaperone for iron
this iron protein travels through blood to target intestinal cells and macrophages; binds to ferroportin leading to degradation; "deletes" extra iron when too much intracellular iron
these (two of them) iron protein remove free hemoglobin and heme from blood and transport them to the liver
haptoglobin and hemopexin
this iron protein is the major storage protein; stores iron in ferric ion state (Fe3+)
this iron protein is another chaperone for iron
what are the characteristics of iron deficiency anemia?
Iron-deficient anemia causes serum iron and serum ferritin to plummet and serum transferrin to raise dramatically. Without enough iron and stores of iron (ferritin), transferrin (the major transporter of iron) raises because it is so desperately searching for iron to transport around in the body.
what are the early signs of iron deficiency as compared to late signs?
1) decrease in iron stores
2) decrease in circulation iron
3) free protoporphyrin concentrations in RBC and transferrin receptors rise
okay. praise Jesus, we are complete finally