SYLLABUS 22: Amino Acids as Precursors to Molecules (other than ntds and catecholamines)

Question 1

functions of aa?

Answer 1

1. protein synthesis
2. energy production
3. synthesis of biochemicals
4. synthesis of purines, pyrimidines
5. synthesis of other compounds

Question 2

what is glutathione? what is its structure?

Answer 2

the most abundant biochemical in most cells

most important cellular antioxidant, also imp in cellular redox control

is a tripeptide

functions in DNA synthesis and repair, protein synthesis, iron synthesis, prostaglandin synthesis, amino acid transport, enzyme activation

Question 3

how is glutathione synthesized?

Answer 3

from glutamate, cysteine, and glycine:

1. glutamate + cysteine make gamma-glutamyl cysteine by enzyme gamma-glutamyl cysteine synthetase

**rate limiting enzyme **of the pathway

uses ATP -> ADP + Pi

2. glycine + ATP -> ADP + Pi via glutathione synthetase

makes GSH, glutathione

Question 4

what is unique about interactions between glutamate and GSH?

Answer 4

gamma carboxyl group of glutamate makes the important bond w/ gamma-glutamyl-cysteine, rather than the alpha carboxyl group, which is unique

Question 5

how does GSH function in cellular redox control?

Answer 5

maintains sulfhydryl-disulfide equilibrium:

2GSH + R-S-S-R’ -> GSSG + RSH + R’SH

Question 6

if GSH functions as an antioxidant, how does it change and how does it return to GSH?

Answer 6

GSH becomes GSSG

it is reduced back to GSH by glutathione reductase

Question 7

is trytophan essential or nonessential aa?

Answer 7

essential

Question 8

what important molecules can tryptophan become?

Answer 8

1) niacin, which becomes NAD and NADP
2) serotonin, crucial neurotransmitter
3) melatonin, another important neurotransmitter

Question 9

how is NAD / NADP generated?

Answer 9

tryptophan -> niacin -> NAD or NADP

Question 10

how is serotonin made?

Answer 10

tryptophan undergoes

1. tryptophan hydroxylase
2. 5’hydroxy tryptophan decarboxylase reacitons

uses PLP as cofactor

releases CO2

makes serotonin

Question 11

what is serotonin

Answer 11

major neurotransmitter and major vasoconstrictor

important in blood pressure regulation, mood, depression

Question 12

how is melatonin made

Answer 12

serotonin in made from tryptophan

serotonin is converted to melatonin in a 2 step pathway

1. acetyl CoA acetylates serotonin

uses THB -> DHB as cofactor

makes n-acetyl serotonin

2. N-acetyl serotonin acted on by SAM with PLP, Vit B12 as cofactors

makes melatonin

Question 13

what is melatonin

Answer 13

brain neurotransmitter important in regulating dark/light cycling so biological clock, appetite, mood

also an important antioxidant

Question 14

what cofactors are used in tryptophan metabolism

Answer 14

PLP, THB, SAM, BH4 (Vit. B12)

Question 15

waht aa does milk contain a lot of? effect?

Answer 15

tryptophan

makes melatonin

makes sleepiness

Question 16

what does tryptophan deficiency in diet cause?

Answer 16

metabolic disease, pellagra

associated w/ energy impairment, weakness, poor motor control, cardiovascular and neurological problems, death

Question 17

how to treat pellagra?

Answer 17

give tryptophan or vitamin niacin in the diet

thus generate the NAD and NADP for so many metabolic pathways

Question 18

what deficiency did people develop during the depression re: their diets

Answer 18

pellagra b/c of tryptophan deficiency b/c ate lots of corn for protein

Question 19

how is trytophan metabolized in the brain?

Answer 19

by tryptophan hydroxylase, to 5-hydroxytryptophan

Tryptophan + O2 + THB -> 5’hydroxytryptophan + H2O + DHB

Question 20

what are all the metabolic uses of THB as a cofactor?

Answer 20

THB: tetrahydrobiopterin (BH4)

important reductant cofactor for many pathways

1. phenylalanine -> tyrosine
2. make catecholamines
3. make serotonin, melatonin

Question 21

what is creatine

Answer 21

an important cofactor

made of glycine, amidino group of arginine, and methyl group from arginine via SAM

Question 22

describe creatine metabolism mechanism

Answer 22

1. glycine in the kidney + SAM + part of arginine form creatine in the liver
2. creatine undergoes creative phospho kinase, CPK, reaction, ATP->ADP. this is reversible!

produces creatine phosphate, a high energy compound

3. creatine pohsphate is stored in muscle, heart, and brain
4. creatine phosphate can break down to creatinine

creatinine is secreted in the urine, is indicative of kidney function, urine flow

Question 23

what does CPK reaction produce

Answer 23

ATP

Question 24

where is creatine P stored

Answer 24

muscle, heart, brain

Question 25

how does creatine impact blood flow

Answer 25

when blood flow’s impeded, so clots or stroke occurs, creatine P provides some ATP for energy if oxidative phosphorylation is impeded

Question 26

what is creatinine

Answer 26

breakdown product of creatine P

secreted in the urine and its level in the urine is indicative of kidney function, urinary flow

Question 27

how can CPK be used in diagnosis?

Answer 27

different isoforms of CPK exist in different tissue, so heart vs. muscle - if see elevation of heart CPK indicates heart attack, if see elevation of brain CPK indicates stroke

Question 29

why is creatine phosphate important

Answer 29

it’s a storage form of ATP

very important in energetics - when have heart attack or stroke, and tissue is deprived of ATP for any period of time >1 minute, damage occurs

Question 30

describe glutamate decarboxylase reaction

Answer 30

glutamate can be decarboxylated by glutamate decarboxylase to form GABA, gamma-amino butyric acid, a major inhibitory neurotransmitter

Question 32

action of histadine DC?

Answer 32

Histidine -> Histamine, a vasodilator

Question 33

functions of histamine

Answer 33

vasodilator

present in individuals w/ inflammation and allergic attacks

also promotes secretion of pepsin and HCl

is important in protien digestion in the stomach

Question 34

function of antihistamines

Answer 34

prevent the vasodilatory effects of too much histamine

Question 35

what might an anti-ulcer drug target

Answer 35

histamine in the stomach

b/c histamine is important in digestion

anti-ulcer drugs are used to inhibit aciton of histamine in stomach, inhibit proteases

Question 36

function of serine DC?

Answer 36

Serine -> EThanolamine

this is a major base in phospholipid phosphatidyl ethanolamine membrane structure

Question 37

function of ornithine decarboxylase?

function of products?

Answer 37

Ornithine -> putrescine -> polyamines spermine and spermidine

these are nitrogenous bases that help to stabilize and bind to DNA, esp during DNA replication

Question 38

what do decarboxylases use as their cofactor?

Answer 38

PLP, which is from B6

Question 39

how is nitric oxide made

Answer 39

1 step from enzyme NO synthase:

arginine + NADPH + H+ -> citrulline + nitric oxide

citrulline enters urea cycle, goes back to arginine

THB is the reductant for the reaction and then NADPH

Question 40

function of NO?

Answer 40

vasodilator

regulator of blood pressure and blood flow

prevents platelet aggregation

Question 41

what is nitroglycerin

Answer 41

pill that releases nitric oxide when placed under the tongue

to reduce the pain and discomfort from heart attacks and poor blood flow

Question 42

what function does NO have w/ bacteria

Answer 42

powerful anti-bacterial agent

reacts w/ heme-containing enzymes to block oxygen activate, eg cytochrome oxidase or cytochrome P450

however this also impacts mammalian enzymes

Question 43

nitroc oxide function in brain

Answer 43

neurotransmitter

Question 44

how does viagra work

Answer 44

contains nitric oxide

vasodilator and blood pressure increases