1: Vitamins + Coenzymes

which vitamins are water soluble?

BC

which vitamins are fat soluble?

ADEK (you STORE stuff in your attic— you can store vitamins within fat if lipid soluble)

which vitamins are water soluble?

BC (think antient times cant store)

how many vitamins do we need to find outside through diet? (essential)

13 (we can make vitamin D but not enough on own)

what is a characteristic of all water soluble vitamins (BC)?

hydrophilic so will have groups that can react with water such as hydroxyls (OHs) and charges

where are fat soluble vitamins stored and do they have fast or slow clearance?

fatty tissue and liver

SLOW clearance because they are stored and not cleared away in urine

an enzymes function is LIMITED by the chemical properties of the encoded

amino acids

enzymes use __________ to perform reactions impossible to do with amino acid sidechains alone

are these molecules composed of polypeptide chains? (are they proteins?)

COFACTORS

NON PROTEIN

what are the two types of cofactors?

metal ions and coenzymes

are co-enzymes a type of cofactor or are cofactors a type of co-enzyme?

coenzyme is a type of cofactor

Mg2+ Fe2+ Zn2+ are bound in the _________ of enzymes to facilitate formation of the _______ state by tuning the positioning of the reaction substrates typically with their POSITIVE charge

active site

transition

coenzymes are small _______ molecules

organic

the active site of the human carbonic anhydrase II enzyme includes a bound _____ ____

zinc ion

which type of coenzyme is tightly bound to the enzyme and chemically unchanged by the catalyzed reaction?

prosthetic group

coenzymes that are loosely associated with the enzyme and behave as a second SUBSTRATE must be presented in __________ ratios with other substrates

stoichiometric

in the formation of acetyl CoA from pyruvate, why isn’t coenzyme A considered a prosthetic group enzyme

it does not remain unchanged but is consumed meaning you can only go through the reaction once with each coenzyme A

list the 8 essential vitamin Bs

1. thiamine

2. riboflavin

3. pyridoxine

4. nicotinic acid (niacin)

5. pantothenic acid

6. biotin

7. folic acid

8. cobalamin

which coenzyme is produced by thiamine (B1)?

what does it do?

thiamine pyrophosphate (TPP)

transfers aldehydes

which coenzyme is produced by riboflavin (B2)?

what does it do?

Flavin Adenine Dinucleotide (FAD)

oxidation- reduction

which coenzyme is produced by pyridoxine (B6)?

what does it do?

pyridoxal phosphate

transfers group TO or FROM amino acids

which coenzyme is produced by nicotinic acid (B3)?

what does it do?

nicotinamide adenine dinucleotide (NAD+)

which coenzyme is produced by pantothenic acid (B5)?

what does it do?

coenzyme A

acyl- group transfer (double bond OR)

which coenzyme is produced by biotin (B7)?

what does it do?

biotin-lysine adducts

ATP dependent CARBOXYLATION (add CO2) and carboxyl group transfer

which coenzyme is produced by folic acid (B9)?

what does it do?

tetrahydrofolate

Transfer of one- carbon components + thymine synthesis

which coenzyme is produced by Cobalamin (B12)?

what does it do?

5-deoxyadenosyl cobalamin

transfer methyl groups AND intramolecular REARANGEMENTS

which order are the vitamin precursors involved in the conversion of pyruvate to acetyl CoA?

Thiamine (B1) = TPP

Nicotinic Acid / niacin (B3) = NAD+

Pantothenic Acid (B5) = Coenzyme A

• most abundant protein in mammals accounting for 25-30% of total mass

• main fibrous component of skin, bone, tendon, cartilage, and teeth

collagen

which three amino acids are abundant in collagen?

glycine (every third)

proline

HYDROXYproline

collagen is formed by THREE helical ________ ______ each in an _______ conformation

what is true about each individual collagen strand?

steric repulsion of _________ rings from the _______and ______residues stabilizes each helix

polypeptide chains

extended

NO H BONDS

pyrroline, proline, hydroxyproline

what keeps the three polypeptide strands of the triple helix of collagen together? ]

which amino acid fits in the interior of the triple helix?

what is another name for the triple helix?

• hydrogen bonds between the strands not WITHIN strands

• glycine

• rope-like SUPER helix

which vitamin is essential for the formation of collagen?

C

SEQ vitamin C role in collagen synthesis

1. ___________ molecule is synthesized

2. _______ WITHIN this molecule is hydroxylated

3. the hydroxyl group of the _________ forms interchains HYDROGEN BONDS that help stabilize the triple-stranded helix

procollagen

proline

hydroxyproline

what is another word for vitamin C?

which coenzyme is the ionized from of vitamin C

which reaction does it help to catalyze?

ascorbic aid

ascorbate

hydroxylation of proline alongside prolyl hydroxylase

improved vitamin C supplements are often an ________ SALT

ascorbate

the hydroxylation of the proline residue due to ascorbate CONVERTS ascorbate to __________

dehydroascorbic acid

how exactly does ascorbate catalyze the hydroxylation of proline residues on procollagen?

activates inactive Fe3+ to active Fe2+ of prolyl-4 hydroxylase

scurvy is a result of a vitamin ___ deficiency

• irritability, joint pain, weakness

• easily bruised, rough skin, loose teeth

C

scurvy is a result of a vitamin ___ deficiency

C

ascorbate regenerates active _______- _______ enzyme through the conversion of its metal ion cofactor Fe+

NO ascorbate leads to buildup of __________ and decreased levels of ____________

how does this lead to scurvy?

• prolyl-hydroxylase

• inactive Fe2+ (prolyl-hydroxylase)

• hydroxylated prolines

• without hydroxylated prolines you cant form hydrogen bonds between the three strands of collagen super helix

is collagen degraded in healthy tissue?

how long does a complete collagen turnover (replacement) take?

what causes scurvy symptoms to develop and worsen?

• yes it is continuously degraded AND replaced

• months to years

• accumulation of defective collagen without hydroxylated proline

what happens as collagen is replaced?

tissues lose structure and rigidity (lose hydroxylated prolines)

POLLEV: why wouldn’t taking supplemental hydroxyproline amino acids help a patient with scurvy?

in the formation of collagen, the prolines are hydroxylated AFTER they have formed the triple helix (procollagen

hydroxylation which is possible by ascorbate (ionized vitamin C) allows for additional hydrogen bonds to form between the triple helix strengthening collagen

beriberi is a ______ and _______ disorder with symptoms including

• swelling in legs and abdomen

• pain in limbs

• muscle weakness

• mental confusion

• heart enlargement

neurologic and cardiovascular

Thiamine (B1) is a precursor to the coenzyme __________

Deficiency in Vitamin B1 can lead to

Thiamine Pyrophosphate (TPP)

BeriBeri

Thiamine pyrophosphate (TPP) is critical for central carbon metabolism in which 3 ways

1. glycolysis

2. TCA cycle

3. Amino Acid Catabolism

thiamine pyrophosphate is the coenzyme to which 2 enzymes?

pyruvate dehydrogenase and a-ketoglutarate dehydrogenase

since thiamine pyrophosphate (TPP) is the coenzyme to pyruvate dehydrogenase and a-ketoglutarate dehydrogenase

what would a deficiency in vitamin B1 result in?

increased levels of pyruvate and a-ketoglutarate BECAUSE the enzymes are inactivated without the coenzyme which is produced by Vitamin B1 (thiamine)

would you see increased or decreased levels of acetyl CoA and succinyl CoA if Thiamine Pyrophosphate (TPP) levels were decreased?

decreased as they are the products of pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase

why do the symptoms of mercury and arsenic poisoning cause similar effects as beriberi?

arsenite chelation inhibits the pyruvate dehydrogenase complex

preventing the activation of TPP which activates the enzyme

how can one treat arsenic and mercury poisoning that result in beriberi symptoms?

add sulfhydral groups to compete with the mercury or arsenite to allow for pyruvate dehydrogenase to be activated by TPP

a deficiency in which enzyme leads to anemia?

Cobalamin (B12)

blood cells require _________ to proliferate which is why a deficiency will lead to anemia

cobalamin (B12)

would low cobalamin levels lead to enlarged (megaloblastic) or shrunken red blood cells

B12 deficiency = megaloblastic LARGE red blood cells

cobalamin causes nuclear hyper_____________ of DNA in NEUTROPHILS (white blood cells

why?

segementation

cobalamin (B12) helps with blood cell proliferation

is cobalamin a coenzyme?

NO but it is a precursor for many coenzymes such as methylcobalmin and cyanocobalmin

what type of reactions do the coenzymes produced by cobalamin catalyze?

rearrangement reactions

A group on one carbon is exchanged with a proton on an adjacent carbon

this is made possible because of which coenzyme?

cyano or methyl cobalamin

Cobalamin is a coenzyme for

1. methyl malonyl-CoA mutase

2. methionine synthase

what are these two reactions responsible for?

OVERALL a cobalamin deficiency disrupts the _______ cycle responsible for nucleotide synthesis and cell proliferation

1. fatty acid degradation

2. remethylating of homocysteine

FOLATE

POLLEV:

Since methyl cobalamin (B12) is the coenzyme which catalyzes the conversion of

• methyl H4 folate —> H4 folate (B12 takes methyl away)

• homocysteine —> methionine (methylated B12 transfers methyl to make methionine)

then a deficiency in B12 would lead to an increase in ?

homocysteine and METHYL H4 folate

B12 is not taking away the methyl from H4 folate AND methyl B12 is not transferring methyl to homocysteine

both humans and e.coli NEED vitamins but why do humans require more essential vitamins through their diet?

e.coli are able to create vitamins on their own and humans have lost the ability to synthesize enzymes required to make complex vitamins

it is much more efficient to eat vitamins then make them

vitamin D3 can be synthesized from _________ by ultraviolet light from sunlight exposure

CHOLESTEROL

SEQ Vitamin D synthesis

1. 7-dehydroCHOLESTEROL converted to ___________ using UV light

2. vitamin D3 is converted to which hormone? (active form of vitamin D3)

   HOW and WHERE does this conversion take place?

3. does vitamin D3 break or build bone?

1. pre-vitamin D3

2. calcitriol, hydroxylation of previtamin D3 in liver and kidneys

3. build

nonessential amino acids can be synthesized from other nutrients

where does the carbon skeleton of amino acids come from?

intermediates of

• glycolysis

• pentose phosphate pathway

• TCA pathway

there are a total of 20 amino acids

do humans or microorganisms have more non-essential amino acids?

microorganisms have more

humans have lost the ability to synthesize them on their own

1. oxaloacetate

2. pyruvate

3. ribose 5- phosphate

4. a-keto glutarate

5. 3-phosphoglycerate

6. phosphoenolpyruvate

are all major ____________ __________ that give rice to amino acids which then give rise to other amino acids

metabolic precursors

would non-essential or essential vitamins have more biosynthetic steps? why?

essential is more complicated because our bodies no longer have the enzymes to be able to create those amino acids on our own so we must find them elsewhere