Biochem Exam 3

Front 1

composition of chylomicron

Back 1

80-90% triglyceride, 10-15% phospholipid, < 5% cholesterol

Front 2

colipase

Back 2

helps pancreateic lipase (which function sin associating with the lipid droplet) bind to micelles

Front 3

purpose of the hydrophilic side of bile

Back 3

allows for the emulsification property of bile

Front 4

how is LPL (lipoprotein lipase) held to the vessel wall

Back 4

by ionic interactions, can be displaced by heparin, useful to assess LPL activity

Front 5

RBCs energy supply

Back 5

RBCs uses only glucose, and therefore only glycolysis

Front 6

brain energy supply

Back 6

uses mostly glucose, never chylomicrons but will use ketones, use chylomicrons mostly for structure

Front 7

what percent of bile is reabsorbed

Back 7

80-90%

Front 8

adipocytes and glucose utilization

Back 8

needs insulin to have glucose enter adipocytes, does not undergo glycogen formation, responsible for producing fatty acids

Front 9

how does insulin lower [glucose]

Back 9

through glycogen synthesis (when well fed) and fatty acid synthesis

Front 10

muscle and carbohydrates

Back 10

responsible more so for using fatty acids

Front 11

liver and carbohydrates

Back 11

makes glycogen, goes through HMPS to make lots of NADPH and RNA and DNA synthesis, can use fatty acids and make them as well

Front 12

sources of C2 in liver utilization of carbs

Back 12

initially gets energy from fatty acids, then eventually through free glucose in the blood as the glucose levels begin to INC

Front 13

where does glycerol come from

Back 13

DHAP and glycerol kinase

Front 14

where are the C2s used?

Back 14

used in fatty acid synthesis, if saturated in the cycle, then can also use for cholesterol synthesis

Front 15

vegetables and cholesterol

Back 15

chol. not found in vegetables

Front 16

dietary input and cholesterol levels

Back 16

complete removal of cholesterol from diet only lowers [cholesterol] by 10-15%, the majority of the cholesterol comes from carbohydrate intake

Front 17

normal blood glucose level

Back 17

70-100%, 4mM, pretty constant with time

Front 18

time course for the regulation of blood sugar

Back 18

with time when last ate at t=0, ycogen degradation occurs at about 12-24 hours, early on there is also lipid degradation which is used up as well, spares blood sugar, amino acids are relatively low in concentration, fit in after glycogen degradation is almost all used up (is glucose sparring and utilizes gluconeogenesis), within 24 hours INC cortisol levels which mobilizes proteins out of muscles (probably start with structural proteins like collagen), induces proteolysis

Front 19

ways that free amino acid utilization can maintain sugar level

Back 19

gluconeogenesis and can spare glucose like lipids do that come in at acetyl CoA

Front 20

cortisol does what to enzymes

Back 20

INC the concentration of transaminases, gluconeogenesis and urea cycle, makes mRNA, blocked by eating

Front 21

how long can one live with only water and electrolytes

Back 21

about 60 days, increases to about 75 days when vitamins are taken, if one loses about 1/3 of their N, then death is irreversible

Front 22

brain and glucose

Back 22

has the greatest need for glucose, has 100% dependence on glucose, need about 70-100 mg%, needed to satisfy brain

Front 23

liver and glucose

Back 23

liver provides glucose, pancreas secretes glucagon to release glucose from glycogen, adrenal medulla releases stressed induced epinephrine which inhibits insulin release, but never use up all the glycogen in the liver,

Front 24

muscle and glucose

Back 24

is glucose sparring, adrenal medulla is stimulated to mobilize glucose from glycogen, has no glucagon receptors, prefers fatty acids, only uses glucose if anaerobic,

Front 25

hormone-sensitive lipase

Back 25

inhibited by insulin, stimulated by glucagon, epinephrine, cortisol, ACTH and GH, is lipid mobilizing (adipokinetic), turns triglycerides into FFA and glycerol, FFA then binds to albumin which cannot cross BB barrier, can enter the muscle and undergo beta-oxidation, does not enter RBC because they lack mito (which is needed for beta-oxidation)

Front 26

liver and fatty acid usage

Back 26

use some fatty acid and uses for own energy for TCA cycle, uses excess C2s to make ketones that can go to the brain, muscle and kidney, the brain shifts its glucose dependence to about 20% and ketone dependence to about 80%, same for the muscle when it uses ketones under aerobic conditions

Front 27

HMG-SCoA lyase

Back 27

once HMG-SCoA is made, lyses this C6 compound into a C2 unit (acetyl CoA) and a C4 unit (acetoacetate, a beta-keto-acid), this C4 unit can be reduced by NADH to form beta-hydroxy acid (beta-hydroxy butyrate), interchangeable with each other, these two C4 units are the ketones, the beta-hydroxy is more prevalent (80%)

Front 28

do you make ketones and cholesterol at the same time?

Back 28

NO, make cholesterol during the well-fed state, make ketones during the starvation state

Front 29

how are ketones utilized in other parts of the body (brain, muscle) and not in the liver?

Back 29

the ketones are activated with CoA by succinyl-SCoA to form an activated ketone and succinate, this is catalyzed by the enzyme succinyl CoA acetoacetate transferase which is present in tissue that use ketones but not present in the liver
1. ketone + succinyl-SCoA -> activated ketone + succinate
a. catalyzed by succinyl CoA acetoacetate transferase

Front 30

ketotic (ketosis)

Back 30

an excess of ketones, occurs when [glucose] is low, if acetoacetate accumulates (as occurs with excessive ketone production), can spontaneously decarboxylate into acetone which is blown off as a waste product, the accumulation of acetoacetate (along with its interchangeable form beta-hydroxy butyrate) can also lead to acidosis (ketoacidosis), acetoacetate and beta-hydroxy butyrate are acids

Front 31

why can’t FAs be used to make glucose

Back 31

because it does not give rise to a net accumulation of OAA

Front 32

order of energy usage in maintaining [glucose]

Back 32

glycogen stores -> gluconeogenesis -> adipokinesis -> proteolysis

Front 33

what happens during starvation phase?

Back 33

there is an accumulation of acetyl-CoA (C2 units), these C2 units turn on pyruvate carboxylase to turn Pyr into OAA, acetyl-CoA must be present to activate Pyr carboxylase, use fatty acids first then amino acids

Front 34

cortisols role in proteolysis

Back 34

stimulates proteolysis, glucose from breakdown of proteins, breaks down both structural (first) and enzymatic (next) proteins to INC aa available in the pool for glucose production (gluconeogenesis)

Front 35

breathing and pH

Back 35

if pH is low then breathe lots (Kussmal)

Front 36

what happens in [glucose] and [ketone] levels are excessively high

Back 36

coma

Front 37

insulins effect on different parts of the body

Back 37

liver: stimulates glycogen and fatty acid synthesis (activates acetyl-CoA synthetase), takes about 100 microU/mL
muscle: stimulates glycogen synthesis, 3-4X INC in glucose uptake, takes about 50 microU/mL
adipocytes: stimulates glucose uptake and inhibits HSL, takes about 10 microU/mL for uptake and 1 microU/mL for breakdown

Front 38

Type I diabetes

Back 38

don’t make insulin, used to be called juvenille onset

Front 39

type II diabetes

Back 39

tissue doesn’t respond to insulin, late onset

Front 40

complications of have blood sugar at <100 microU/mL in diabetics

Back 40

hyperglycemia-when glycogen and fatty acid aren’t made
glycosylation-glucose glycosylates proteins (albumin, hemoglobin)
cataracts-reduction of glucose to glucitol, polymerizes and clouds lens
microangiopathies-aneurisms, problems with capillary beds, can view this in the eye, also says if there is problem with kidney

Front 41

polyuria

Back 41

lots of urine, associated with diabetes

Front 42

polydipsia

Back 42

dehydrated, drink a lot, complication of polyuria

Front 43

complications of having blood sugar at <50 microU/mL

Back 43

muscle weakness during exercise (anaerobic metabolism), this occurs because glycogen can’t be made

Front 44

complications of having blood sugar at <10 microU/mL

Back 44

hyperlipemia-INC lipids in blood and switch to ketosis

Front 45

complications of having blood sugar at <1 microU/mL

Back 45

ketosis and acidosis, inhibit HSL

Front 46

glycosuria

Back 46

excess glucose in urine

Front 47

when does ketosis begin

Back 47

6-12 hours after meal, when amino acid is beginning to be used, shift towards a gluconeogenic state

Front 48

functions of amino acids

Back 48

1. proteins-structure/enzymes/hormones/transporters/immunoglobulins
2. neurotransmitters-GLN, GLU, TYR, TRP, GLY
3. gluconeogenesis-urea cycle
4. energy-TCA cycle
5. sphingolipids-serine
6. hormones-TYR -> thryoxine, epinephrine
7. phospholipids
8. nucleotides
9. heme (gly-succinoyl-CoA)
10. vitamin B3-nicotinamide biosynthesis (TRP), niacine

Front 49

essential amino acids

Back 49

FVT WIM HRLK

Front 50

protein turnover

Back 50

for insulin, half-life (T/2) is 20 mins, for dentine (teeth) and crystalline (eyes) half-life is a lifetime, on average 1-2% is degraded/24 hours, 20% of protein is excreted/degraded per day or about 30 grams loss/day (~1 oz. required for replacement 1/10 lb.), 80% is recycled

Front 51

total amount of protein in body

Back 51

~10 kg

Front 52

how are amino acids loss?

Back 52

1. can be lost intact (urea)
2. creatinine loss (Gly, Arg, Met)-~3-10 gm/day

Front 53

Urea

Back 53

bulk of the amino acids loss, MW= ~60 gm/mol, 50% N

Front 54

amino acids and amino acid loss

Back 54

~15% N, therefore 15% of 30 gm of nitrogen in amino acids is lost then ~10 gms or urea is produced from 30 gm of amino acids

Front 55

humans and amino acid loss

Back 55

man usually makes ~30 gm urea/day, we ingest 90-100 gms of protein/day, total loss of about 30 gms urea, 10 gms creatinine and 40 gms total/day

Front 56

protein degradation

Back 56

no digestion occurs in the mouth, when in the stomach there is acid hydrolysis (produced from parietal cells) and pepsin (produced from chief cells as pepsinogen which is activated by high [H+]

Front 57

pepsin

Back 57

cleaves basic aa (Lys) first but fairly nonspecific (general protease), under zero order kinetics, is an inactivated pepsinogen form, when want to be activated then cleave the tail region that covers the active site which contains two Asp (which have – charge), cleavage occurs when there is protonation of one of the Asp then H2O enters and cleaves the tail with an intrinsic protease activity

Front 58

rennin (chymosin)

Back 58

used in cheese industry, when exposed to milk casein it forms a coagulated milk protein (traps milk in stomach so pepsin can work on it), found in abundant amounts in children but there is very little in adults)

Front 59

what kinds of enzymes from pancreas

Back 59

trypsinogen, chymotrphysinogen, procarboxyg-peptidase, pro-elastase, pro-collagenase

Front 60

protein degradation

Back 60

protein -> polypeptides -> smaller polypeptides -> amino peptidases -> dipeptidases -> amino acids, they then all go to the blood

Front 61

enterokinase

Back 61

activates trypsinogen to trypsin which then activates chymotrypsinogen, pro-carboxypeptidase, pro-elastase, and pro-collagenase, not a kinase but actually a protease, secreted into the lumen of the duodenum

Front 62

basis of allergies

Back 62

allergies of food due to having differences in breaking down small polypeptides, when they enter the bloodstream an allergic reaction is started

Front 63

characteristics of amino acid uptake across GI mucosal cells

Back 63

1. L amino acids only taken up because only use L
2. ATP dependent process
3. Na+ dependent and Na+ independent (some for each type, 2 different mechanisms)
4. specific transporters-(TRP and MET), if these are defective Hartnup’s Disease, basics, neutrals

Front 64

ubiquination

Back 64

adding ubiquitin (76 a.a. polypeptide) to a protein and marking it for degradation, if have Asn on the NH2-end of the protein then the T/2 is short at ~20 mins, if have Met on the end, T/2 is long at ~3 days

Front 65

PEST sequence

Back 65

Proline, Glutamate, Serine, and Threonine, the more PEST sequences on a protein, the shorter the half-life because it is marked for degradation, transaminases are rich in PEST sequences, Vit B6 (pyridoxal phosphate) can block PEST sequence and protect protein from degradation, phosphorylation of serine on PEST sequence prolongs the T/2 of a molecule by blocking sites for phosphorylation

Front 66

molecules with short half-lifes

Back 66

prostaglandins and cyclo-oxygenase

Front 67

which of the essential amino acids can we make

Back 67

M, H, R, these are essential only during illness, pregnancy and growth

Front 68

alanine synthesis

Back 68

1. pyruvate (alpha-keto acid) + alpha amino acid -> alanine (alpha-amino acid) + alpha-ketoacid
a. catalyzed by transaminase (responsible for switching C=O for C-NH2

Front 69

alanine transaminase (ALT)

Back 69

catalyzes the reaction Pyr + AA -> Ala (specific) + alpha-ketoacid (generic), specific for only ½ of the reaction (Ala) generic for the other half (alpha amino acid), is very reversible with a Keq of 1

Front 70

glutamate-pyruvate transaminase (GPT)

Back 70

catalyzes the reaction Pyr + Glutamate -> alanine + alpha-keto glutarate, both halves of the reaction are specific

Front 71

glutamate-oxalacetate transaminase (GOT)

Back 71

catalyzes the reaction Glu + OAA -> alpha-ketoglutarate + Asp, both are specific

Front 72

pyridoxal phosphate

Back 72

the handle of the transaminase, needed by the transaminases, needed to carry the N from the amino acid and add it to alpha keto acid, comes from vitamin B6 (pyridoxol) which is phosphorylated with ATP to form pyridoxol-phosphate, then oxidize with NAD+ to form pyridoxal phosphate, the ATP and NAD+ steps order can be switched

Front 73

schiff’s base

Back 73

reaction between primary amine and aldehyde, found in the transaminase mechanism, occurs when the amino group reacts with the transaminase, has water leave and forms the Schiff base intermediate, water then breaks the Schiff base into an alpha keto-acid and leaves the amine on the pyridoxal phosphate (making a pyridoxamine-phosphate)

Front 74

characteristics regarding transaminases

Back 74

1. pyridoxal phosphate used in sphingolipid biosynthesis-80% of amino acid biosynthesis uses this (ser + 16:0~CoA -> sphingolipids), the co-factor
2. schiff’s base weakens bonds to alpha-carbon atom (on the amino acid on the pyridoxal phosphate) allowing:
a. decarboxylation (non-oxidative)-if have C=N move to C-COOH, can weaken that bond and have decarboxylation, metal ions (esp. Ca++, Mg++) can prevent decarboxylation, can stabilize COOH and keep it on the amino acid
b. beta-gamma elimination-have C=N move to R=C and then move to gamma C to weaken the bond between beta and gamma C
c. deprotonation-have C=N move to C-H and have deprotonation
d. transamination

Front 75

aspartate synthesis

Back 75

Glu + OAA -> alpha-ketoglutarate + Asp, catalyzed by GOT, a C4, aspartate from OAA

Front 76

glutamante synthesis

Back 76

Pyr + Glu -> alpha-ketoglutarate + Ala, catalyzed by GPT, a C5, glutamate from alpha-keto glutarate

Front 77

asparagine synthesis

Back 77

1. Asp + Gln -> Asn + Glu
a. catalyzed by transamidase, tends to go forward, have to force backward, but don’t make Gln this way
b. mammalian
2. Asp + NH4+ -> Asn
a. catalyzed by Asn synthetase
b. use ATP -> AMP + PPi -> 2 Pi
c. found in prokaryotes, this enzyme is not in humans

Front 78

uses of asparagine

Back 78

used in protein synthesis and not in metabolism, is glycosylated in the ER, N-linked glycosidic bond

Front 79

glutamine synthesis

Back 79

1. glutamate + NH4+ + ATP -> Gln + ADP + Pi
a. catalyzed by glutamine synthetase
b. high levels of NH4+ is toxic to the body
c. glutamine is more easily transported across the membrane than glutamate is
d. allows for C’s to be transferred out of the cell, but it also takes a toxic NH4+ with it in a detoxified form
2. backwords reaction catalyzed by glutaminase, making Glu from Gln, not completely reversible but can go backwards, does not make ATP, releases NH4+

Front 80

glutamate dehdyrogenase

Back 80

an alternate way to make glutamate, alpha-ketoglutarate + NH4+ + NADH -> Glu, an alternative way to detoxify NH4+, reversible

Front 81

liver and glutamine

Back 81

does the reverse reactions of the muscle that converts alpha-ketoglutarate into Gln, converts Gln -> Glu + NH4+, then converts Glu -> alpha-keto glutarate + NH4+ + NADH, these two NH4+ can combine to form urea, alpha-keto glutarate enters TCA cycle and makes OAA which can be turned into glucose which leaves the liver and reenters the muscle, brain, RBC and other tissues

Front 82

serine synthesis

Back 82

glycolysis leads to 3-PGA
1. 3-PGA + NAD+ -> NADH + alpha-ketoacid
2. alpha-keto acid + amino acid (may be Glu or Asp) -> alpha keto-acid + phosphoserine
a. catalyzed by a transaminase
3. phosphoserine -> serine + P

Front 83

glycine synthesis

Back 83

1. from serine-
a. Ser + THF -> Gly + N5, N10 methylene THF
i. catalyzed by serine hydroxy methyl transferase
2. de novo from methylene THF-
a. methylene THF + CO2 + NH4+ + NADH -> glycine + NAD+
i. catalyzed by glycine synthase
ii. this glycine can then be made into serine
3. from choline-
a. choline is oxidized to aldehyde and oxidized to an acid, forms betaine
b. betaine -> dimethylglycine + CH3
i. this methyl group can be donated to homocystein to make Met, can donate methyl via SAM to things like epinephrine, leftover becomes homo-cysteine, which can then repeat the cycle
c. dimethylglycine can then lose two CH3 to 2 THF to form glycine
4. threonine-can be split into glycine and acetaldehyde (which is converted first to acetate, then to acetyl-CoA
a. catalyzed by threonine aldolase

Front 84

tetrahydrofolate (THF)

Back 84

composed of pteridine ring (from folate, is the two ring compound of THF), PABA (paraamino benzoic acid) and Glu (may have 5-7 of them), can pick up C’s at varying levels of oxidation, a good handle for C on intermediate oxidation levels

Front 85

different forms of one carbon metabolism

Back 85

1. methyl form-SAM (SAM can methylate Norepinephrine (from Tyr) into epinephrine)
2. alcohol, aldehyde, and acid form-THF, good handle for C on intermediate oxidation levels
3. CO2 form-biotin, can put CO2 onto something, used in pyruvate carboxylase, acetyl CoA carboxylase and propionyl CoA carboxylase

Front 86

Folacin

Back 86

pteridine-PABA-glutamate (can’t make this de novo, bacteria can in our stomach)

Front 87

PABA analog

Back 87

sulfonamide, used as a way to counteract bacteria from making folacin, doesn’t hurt us, but only bacteria

Front 88

methylene THF

Back 88

can be oxidizes once to aldehyde or twice into an acid, can also be reduced to CH3, methylene THF can get 1-C donor from Ser or His (oxidized form of C as an aldehyde),

Front 89

methionine synthesis

Back 89

methionine is essential, can make it though with homocysteine + CH3 from betaine -> dimethylglycine, depends on the availiability of C’s and homocysteines, nutritional state of the body

Front 90

why are there so many glycine biosynthesis pathways

Back 90

15% of body mass = protein
1/3 of that (5%) = collagen
1/3 of that (1-2%) = glycine (1/7 of protein is glycine)

Front 91

cysteine synthesis

Back 91

1. methionine + ATP -> S-Adenosyl Methionine (SAM)
a. Met attacks ATP at alpha phosphate, beta and gamma is loss as 2 Pi
b. the S on SAM has three bonds with one bond to AMP and a + charge
2. SAM -> S-Adenosyl homocysteinne (SAHcys) + CH3
3. SAHcys -> adenosine (AMP) + homocysteine
4. homocysteine has two fates
a. homocysteine + betaine -> methionine + dimethyl glycine
b. homocysteine + serine -> cystathionine + H2O
i. catalyzed by cystathionine synthase
ii. attack at C bonded to OH
c. cystathionine -> alpha-aminobutyrate + cysteine
i. catalyzed by cystathionase

Front 92

tyrosine synthesis

Back 92

1. phenylalanine + O2 -> tyrosine
a. catalyzed by mixed function oxidase (MFO), AKA is monooxygenase, brings in something reduced (THB, tetrahydrobiopterin) and oxidizes it (DHB), THB is regenerated when DHB is reduced by NADH
b. half O2 goes to tyrosine other half forms H2O
c. hydroxylation reaction
2. tyrosine can be used as neurotransmitters, melanin and thyroxine

Front 93

tetrahydrobiopterin (THB)

Back 93

gives off 2H+ in the tyrosine synthesis reaction becoming DHB, catalyzed by phenylalanine hydroxylase (PH)

Front 94

Phenylketouria (PKU)

Back 94

individuals that have a deficient phenylalanine hydroxylase, cannot turn excess Phe into Tyr, Phe accumulates, Phe through transaminase + alpha ketoglutarate -> glutamante by phenyl pyruvate, reduction of phenyl pyruvate leads to phenyl lactate and decarboxylation of that can form phenyl acetate, these three phenyls are phenylketones, phenylketones are toxic to developing brain and heart

Front 95

proline synthesis

Back 95

1. Glu + NADH -> Schiff’s base intermediate (glutamate semi-aldehyde) + NAD+
2. glutamate semi-aldehyde + NADH -> proline
a. all these reactions are reversible

Front 96

purposes for amino acid catabolism

Back 96

ingestion, fasting, and starvation

Front 97

liver and amino acid absorption

Back 97

takes in 17/20, doesn’t take val, leu, ile normally, these three enter circulation and go throughout the body, after meal 60% of amino acids are val, leu, ile (branched chain amino acids

Front 98

fate of branched chain amino acids (BCAA)

Back 98

val -> succinyl-CoA
ile -> succinyl-CoA or acetyl CoA
leu -> acetyl CoA
succinyl CoA is used for gluconeogenesis
acetyl CoA is used for TCA cycle and FA synthesis

Front 99

uses of BCAA during fasting/starvation

Back 99

eat protein (98% for protein synthesis and 2% degradation), Ile and Leu contribute to FA, Ile and Val contribute to succinyl CoA which can be converted to succinate which turns ketone bodies into acetoacetyl-CoA

Front 100

ACTH and cortisol

Back 100

hypoglycemia tells the anterior portion of the pituitary gland to release ACTH, ACTH goes to the adrenal gland and tells the cortex to release cortisol and the medulla to release epinephrine, cortisol affects almost all tissues, can INC gluconeogenesis and transaminase in the liver, INC mRNA set liver up for amino acid usage, in the muscle lysosome membranes become more fragile because of cortisol, releases proteolytic enzymes that breaks down proteins into amino acids (want to get blood sugar levels up)

Front 101

glucose/alanine cycle

Back 101

the 20 a.a.’s reacted with pyruvate and transaminases to form alanine and 20 alpha-ketoacids metabolized by muscle, takes these and turns them into energy for the muscle only (spares glucose, doesn’t make it), alanine from the muscle enters the blood stream (30% of blood amino acids are Ala during starvation) and enters the liver as pyruvate, pyruvate enters gluconeogenesis become glucose and leaves the liver to supply brain, RBC

Front 102

tumors in adrenal gland or pituitary

Back 102

drives the glucose/alanine cycle so much that it leads to hyperglycemia, epinephrine is release in large amounts and blocks insulin release, INC cortisol can lead to lots of muscle wasting

Front 103

glucose/glutamine cycle

Back 103

alanine + alpha-ketoglutarate -> pyruvate and glutamate, pyruvate is used to pick up NH4+ from amino acids, glutamate builds up but cannot leave the muscle, some glutamate loses NH4+ and replenishes alpha-ketoglutarate (through GDH), some glutamate is also turned into Gln with NH4+ which can leave the muscle cell (through Gln synthetase), 20% of blood amino acids is glutamine, goes to liver and the liver turns it into glucose

Front 104

fate of N atoms from amino acuds

Back 104

1. alanine-alanine that enters the liver can be converted (with alpha-keto glutarate) to pyruvate and glutamate (through GPT), glutamate (through GDH) can replenish GDH and release NH4+
2. glutamine-can be turned into Glu through glutaminase and release NH4+, Glu can be turned into alpha-ketoglutarate and also release NH4+, this ammonia builds up and is detoxified and excreted, intestinal mucosa can excrete NH4+ and kidney pisses out some NH4+

Front 105

Urea Cycle

Back 105

occurs in the liver, partly in the mito, partly in the cyto
1. NH4+ + CO2 + 2 ATP -> Carbomyl phosphate + 2 ADP + Pi
a. catalyzed by carbamoyl-phosphate synthetase (CPS-1), mito
2. carbamoyl phosphate + ornithine -> citrulline + Pi
a. catalyzed by ornithing transcarbamoylase (OTC), mito
3. citrulline + Asp + ATP -> AMP + 2Pi + arginosuccinate
a. catalyzed by arginosuccinate synthetase (ASS), cytosol
4. arginosuccinate -> fumarate (C4) + arginine
a. catalyzed by arginosuccinate lyase (ASL), cytosol
5. arginine + H2O -> urea + ornithine
a. catalyzed by arginase, cytosol, renenters the mito

Front 106

citrulline

Back 106

has the ability to leave the mito and enter the cytosol of the lvier

Front 107

arginine

Back 107

although it is essential, can be made in the body depending on the nutritional values

Front 108

notes regarding urea cycle

Back 108

1. occurs in two compartments
2. enzyme-induced during starvation (by cortisol)
3. two nitrogens (from NH4+ and from aspartate)
4. fumarate links urea cycle to the TCA cycle, also a source of H+ pickerupers, fumarate to malate, malate to OAA, OAA to aspartate
5. requires catalytic amounts of ornithine
6. provides pathway for arginine biosynthesis
7. each urea made utilizes 4 ATP (2 at CPS-1, 2 at arginosuccinate synthetase step)
8. disease at each step are known

Front 109

fate of alanine

Back 109

alanine -> pyruvate via ALT (GPT)

Front 110

fate of serine

Back 110

ser -> glycine via THF; serine hydroxyl methyl transferase
ser -> pyruvate + H2O + NH4+ via serine dehdyratase
ser -> cystein via cystathionine
ser -> phsophatidyl serine (-> ethanolamine, choline), sphingolipids (palmitoyl CoA + serine

Front 111

fate of glycine

Back 111

gly -> ser via serine hydroxyl methyl transferase
gly -> CO2, THF, NH4+, NADH via glycine synthase (or glycine cleavage enzyme)
gly -> glyoxalate -> oxalate

Front 112

fate of aspartate

Back 112

asp -> OAA via GOT

Front 113

fate of asparagine

Back 113

asn -> excreted

Front 114

fate of glutamate

Back 114

glu + NAD+ -> NH4+ + NADH + alpha-keto glutarate via GDH

Front 115

fate of glutamine

Back 115

gln -> glu + NH4+ via glutaminase

Front 116

fate of proline

Back 116

pro -> glu -> alpha-keto glutarate (the reverse of synthesis)

Front 117

fate of phenylalanine

Back 117

phe -> tyr via phenylalanine hydroxylase

Front 118

fate of tyrosine

Back 118

tyr -> homogentisic acid (catecholamines, melanin, DOPA, energy)
tyr + alpha-keto glutarate -> alpha-ketoacid (parahydroxy phenylpyruvate)
alpha-ketoacid (parahydroxy phenylpyruvate) + O2 -> CO2 + homogentisic acid via Vit C
parahydroxy phenylpyruvate -> fumarate + acetoacetate (both ketogenic and glucogenic)
parahydroxy phenylpyruvate -> polymer (is black in urine, alcaptonuria)

Front 119

fate of arginine

Back 119

arginine -> ornithine + urea
ornithine + alpha keto glutarate -> semialdehyde + glutamate via transaminase
semialdehyde -> glutamate
glutamate -> alpha keto glutarate via GDH

Front 120

fate of threonine

Back 120

1. threonine -> alpha-ketobutyrate
a. threonine dehydratase
2. alpha-ketobutyrate + CoAsh -> propionyl-CoA + CO2
3. propionyl-CoA + CO2 + biotin -> methyl malonyl CoA
a. carboxylase
4. methyl malonyl CoA -> succinyl-CoA
a. B12 mutase

Front 121

alternative fate of threonine

Back 121

threonine -> glycine + acetaldehyde via threonine aldolase, the acetaldehyde then becomes acetate then finally acetyl-CoA

Front 122

which amino acids enter at the pyruvate level

Back 122

Pyruvate (C3)-ala, ser, gly, cys, trp, thr

Front 123

which amino acids enter at the acetyl-CoA level

Back 123

acetyl-CoA (C2)-thr, leu, ilu

Front 124

which amino acids enter at the acetoacetate level

Back 124

acetoacetate (C4) -> acetyl CoA, amino acids are phe, tyr, trp, lys

Front 125

which amino acids enter at the succinyl-CoA level

Back 125

succinyl-CoA (C4)-thr, met, ile, val

Front 126

which amino acids enter at the fumarate level

Back 126

fumarate (C4)-asp, phe, tyr

Front 127

which amino acids enter at the OAA level

Back 127

OAA (C4)-Asp

Front 128

fate of methionine

Back 128

1. Met + ATP -> SAM
2. SAM -> CH3 (which can be donated) + S(A) Hcys
3. S(A) Hcys -> AMP + Hcys
4. Hcys + Ser -> cystathionine
a. catalyzed by cystathionine synthase
5. cystationine -> cysteine + precursor to alpha-ketobutyrate
a. catalyzed by cystathioninase

Front 129

fate of cysteine (through reduction)

Back 129

two cysteines are joined together by a cysteine bond, responsible for forming pyruvate and H2S
1. proteolysis of a protein -> cystine
2. cystine -> reduced form of cysteine
a. catalyzed by cystine reductase
3. reduced form of cystine -> mercaptor pyruvate
a. catalyzed by transamination
4. mercapto pyruvate + 2H+ -> pyruvate + H2S

Front 130

fate of cysteine (through oxidation)

Back 130

responsible for forming pyruvate and SO4- as a source of sulfur
1. cysteine + O2 -> oxidized form of cysteine
a. catalyzed by dioxygenase
2. oxidized form of cysteine -> pyruvate-SO2
a. catalyzed by transaminase
3. pyruvate-SO2 -> pyruvate + SO3- (sulfite, which can be converted to sulfate (SO4--))

Front 131

uses for S

Back 131

need for CoASH, sulfates used in sulfatides, glycoaminoglycans, conjugation reactions (makes things more soluble)

Front 132

examples of glycosaminoglycans

Back 132

chondroitin sulfate, dermatan sulfate, kertan sulfate, heparin sulfate

Front 133

examples of conjugation reactions

Back 133

bilirubin, hormones, DHEA-S (the stored form of DHEA)

Front 134

how is sulfate trapped?

Back 134

form 3’-Phospho adenosyl 5’phospho Sulfate (PAPS), the activated form for sulfate (need 3 ATPs to make)
1. SO4 + ATP -> Adenosyl Phosphosulfate (APS) + 2 PPi (-> 2Pi)
2. APS + ATP -> PAPS + ADP

Front 135

fate of histidine

Back 135

1. decarboxylation
a. histidine -> CO2 + histamine (catalyzed by histidine decarboxylase)
2. forming glutamate
a. histidine -> NH4+ + urocanic acid (has conjugated double bonds and can observe uv light)
i. catalyzed by histidase
b. urocanic acid + H2O -> FIGLU (formiminoglutamate, composed of glutamate and formimino) (intermediate that has opened ring, found in urine if there is a deficiency in folic acid)
i. catalyzed by urocanase
c. FIGLU + THF -> glutamate + formimino-THF

Front 136

fate of trytophane

Back 136

1. tryptophane + O2 -> kynurenine (open ring)
a. catalyzed by dioxygenase
2. kynurenine is then modified by:
a. remove formate (HCOOH)
b. remove alanine (and convert to pyruvate, glucogenic)
c. deaminate (NH2)
d. decarboxylate (CO2)
e. break ring open with O2 (forms C6 cleaving the benzoic acid), forms alpha-ketoadipic acid
f. oxidative decarboxylation (add SCoA at one end, lose 2 CO2 at both ends) (forms acetoacetyl-SCoA, ketogenic)

Front 137

fate of lysine

Back 137

1. ketogenic
a. lysine + alpha-ketoglutarate -> saccharopine
b. saccharopine -> NH4+ + alpha-amino adipic acid
c. alpha-amino adipic acid -> NH4+ + alpha-keto adipic acid
i. catalyzed by transaminase
d. alpha-ketoadipic acid turns into acetoacetyl-CoA via oxidative decarboxylation (add SCoA at one end, lose 2 CO2 at both ends) (forms acetoacetyl-SCoA, ketogenic)
2. glucogenic
a. slightly glucogenic, lysine is more ketogenic though, an alternate path that we do not need to know about

Front 138

common steps of the branched chain amino acids (BCAA)

Back 138

1. VAL, ILE, LEU undergo transamination first to form branched chain alpha-ketoacids
2. then undergo oxidative decarboxylation to form a completely reduced C with a CoA on the end, acts like a branched cahin fatty acid
3. then undergo the 1st step of beta oxidation (the addition of FAD and add a double bond between the alpha and beta C)

Front 139

valine after the common steps of BCAA

Back 139

1. valine undergoes 3 steps and forms intermediate
2. intermediate undergoes oxidation of C=C to COOH and forms methyl malonyl-SCoA
3. methyl malonyl-SCoA -> succinyl-SCoA
a. catalyzed by methyl malonyl mutase with a vitamin B12 cofactor

Front 140

isoleucine after the common steps of BCAA

Back 140

1. valine undergoes 3 steps and forms intermediate
2. continue with beta-oxidation and add another CoASH to form propionyl-SCoA and acetyl CoA (ketogenic)
3. propionyl-SCoA + CO2 + biotin + ATP -> methyl malonyl CoA
4. methyl malonyl CoA -> succinyl-SCoA (glucogenic)

Front 141

leucine after the common steps of BCAA

Back 141

1. leucine undergoes 3 steps and forms intermediate
2. intermediate is carboxylated with CO2 to form an intermediate
3. that intermediate is split with H2O to form acetyl-CoA and acetoacetate (beta-ketobutyrate, forms 2 acetyl-CoA)
4. LEUCINE IS THE ONLY AMINO ACID THAT IS STRICTLY KETOGENIC

Front 142

Maply Syrup Urine Disease

Back 142

is related to Val, Ile and Leu, genetic defect in decarboxylation step, destroys brain, test urine for branched chain a.a., tell them not to eat Val, Ile, or Leu

Front 143

Functions of Nucleotides

Back 143

1. nucleic acids (DNA, RNA)
2. Energy forms (NMP, NDP, NTP)
3. regulatory (2nd messengers-cAMP, cGMP)
4. activators (UDP-glucose, galactose; CDP-Choline
5. NAD, FAD, CoA, PAPS, SAM (cofactors)
6. Adenylations (for regulation)
7. physiological agents (Adenosine, ATP, ADP released with neurotransmitters), has a direct effect on smooth muscles

Front 144

nucleosides

Back 144

base + sugar

Front 145

nucleotides

Back 145

base + sugar + PO4

Front 146

structures

Back 146

know them 242-243

Front 147

purines

Back 147

two rings, adenine, guanine, hypoxanthine (precursor for xanthine), xanthine, uric acid

Front 148

pyrimidines

Back 148

one ring, cytosine, uracil, thymine, orotic acid

Front 149

names of the bases, nucleosides and nucleotides

Back 149

adenine + sugar -> adenosine + PO4 -> adenylate
guanine + sugar -> guanosine + PO4 -> guanylate
hypoxanthine + sugar -> inosine + PO4 -> inosinate
xanthine + sugar -> xanthosine + PO4 -> xanthylate
cytosine + sugar -> cytidine + PO4 -> cytidylate
uracil + sugar -> uridine + PO4 -> uridylate
thymine + sugar -> thymidine + PO4 -> thymidylate
orotic acid + sugar -> orotidine + PO4 -> orotidylate

Front 150

deoxyribose vs. ribose

Back 150

alpha-D-deoxyribose is missing an OH on 2 C, alpha-D-ribose undergoes a reduction process

Front 151

glycosidic bond

Back 151

for purines is a beta N-glycoside bond between 9-N on purine and 1’C on the ribose
for pyrimidines is a beta N-glycoside bond between 1-N on pyrimidine and 1’C on the ribose

Front 152

phosphorylation of the bases

Back 152

can occur on OH of C 2, 3, or 5, but normally not on 1 position

Front 153

phosphodiester bond

Back 153

connects nucleotides, is a 3’-5’ bond

Front 154

where do the atoms from nucleotide biosynthesis come from

Back 154

memorize, pg 245, biosynthesis occurs during the well fed state, need ribose and energy

Front 155

Purine synthesis

Back 155

1. glucose -> ribose-5-phosphate
a. via HMPS
2. ribose-5-phosphate + ATP -> phosphoribosyl pyrophosphate (PRPP) + AMP
a. catalyzed by pyrophosphoribosyl kinase
3. PRPP + Gln -> Glu + PPi (-> 2Pi) + phosphoribosylamine (PR-NH2)
a. catalyzed by Gln-PRPP amidotransferase
4. PR-NH2 + Gly + ATP -> Phosphoribosyl-glycinamide + ADP + Pi
a. catalyzed by phosphoribosyl glycinamide synthetase
5. phosphoribosyl-glycinamide + formyl-THF (the CH2 is oxidized to CHO) -> intermediate
a. catalyzed by transformylase, if short on folate will have problems with biosynthesis here
6. intermediate + gln + ATP -> intermediate + ADP + Pi
7. intermediate -> intermediate (cyclized form)
a. catalyzed by a cyclase
8. intermediate + CO2 -> intermediate
a. does not use biotin and ATP, catalyzed by a carboxylase
9. intermediate + Asp + ATP-> intermediate + fumarate + ADP + Pi
a. catalyzed by a synthetase
10. intermediate + formyl-THF (as a oxidized CHO, recycled with serine -> gly) -> intermediate
a. a formylation
11. intermediate -> cyclization of intermediate forming inosine mono phosphate (IMP), it is a hypoxanthin ring, the first purine nucleotide

Front 156

inhibition of pyrophosphoriboxyl kinase

Back 156

inhibited by high [ADP] and hi [GDP] concentration, this is a sign of low energy

Front 157

importance of the step catalyzed by Gln-PRPP amidotransferase

Back 157

is the key regulatory (commited step of purine synthesis)

Front 158

regulation of Gln-PRPP amidotransferase

Back 158

inhibition-products of NMP, NDP, NTP (feedback), especially A and G, is additive, A and G inhibiton add together
stimulation-high PRPP (feed forward)
mechanism-doesn’t follow Michaelis-Menten, is sigmoidal shape due to substrate activation or cooperativity, INC velocity with INC in PRPP, shifts to the right in the presence of purine nucleotides (shows a slowing velocity)

Front 159

characteristics of de novo purine synthesis

Back 159

1. there is a sugar handle (PRPP)
2. linear pathway to IMP (branched thereafter)
3. 5 ATP’s required
4. 2 Gln, 2 THF (serines), glycine, CO2, aspartate required
5. highly regulated (2 of them, the key is the formation of PR-NH2, other is creation of PRPP)

Front 160

adenine synthesis

Back 160

1. IMP + Aspartate + GTP -> succinyl adenine
2. succinyl adenine + GTP -> adenine (AMP) + succinate
a. adenine acts as an inhibitor of the key regulatory step in the pathway

Front 161

guanine synthesis

Back 161

1. IMP + NAD+ -> xanthinic acid (XMP) + NADH
a. acts as a way to activate the molecule
2. XMP + ATP + Gln -> guanine (GMP) + Glu

Front 162

reciprocal regulation of purine synthesis

Back 162

ATP blocks A synthesis and stimulates G synthesis, GTP blocks G synthesis and stimulates A synthesis, they reciprocally act as energy source for the other reaction

Front 163

pyrimidine synthesis

Back 163

1. Gln + CO2 + P (from 2 ATP -> 2 ADP + Pi) -> carbamoyl-phosphate
a. catalyzed by carbamoyl phosphate-II (CPS-II)
2. carbamoyl-phosphate + Asp -> Pi + intermediate (ready for cyclization)
a. catalyzed by aspartate trans carbamoylase (ATCase)
3. intermediate -> dihydro-orotic acid (cyclized form)
4. dihydro-orotic acid + NAD+ -> orotic acid + NADH
a. the orotic acid has a double bond between CH and C-COOH
5. orotic acid + PRPP -> orothodylate (OMP)

Front 164

carbamoyl-phosphate II (CPS-II)

Back 164

the key commited step in pyrimidine synthesis, not in mito like in urea cycle, but in the cytosol, activated by ATP (high energy charge), stimulated by PRPP, inhbitied by UMP (1st pyrimidine product)

Front 165

aspartate trans carbamoylase

Back 165

also a committed step, is inhibited by CTP (last pyrimidine product)

Front 166

uracil synthesis

Back 166

OMP -> UMP + CO2
catalyzed by orotidylate decarboxylase, UMP is used to inhibit CPS-II can then be phosphorylated by two ATPs to form UTP,

Front 167

CTP synthesis

Back 167

UTP + ATP + Gln -> CTP + Glu + ADP + Pi
catalyzed by cytidylate synthetase

Front 168

notes for pyrimidine synthesis

Back 168

is completely a linear a pathway and the sugar handle is added after the ring is formed

Front 169

thymine biosynthesis

Back 169

ribose needs to be converted to deoxyribose before uracil nucleotide can be methylated to thymine

Front 170

ribonucleotide reductase

Back 170

Ribose + thioredoxin (has 2 reduced cys) -> 2’-deoxyribose + oxidized form of thioredoxin
catalyzed by ribonucleotide reducatse, requires diphosphate level of nucleotide substrate (not tri- or mono-), must then recycle to get back reduced thioredoxin, use flavoprotein and thioredoxin reductase and oxidize FADH2 to FAD, must then recycle to get back FADH2, use the flavoprotein again and oxidize NADPH to NADP+ to get back FADH2, must the regenerate NADPH and that comes from HMPS and malic enzyme

Front 171

formation of dTMP

Back 171

1. via d-UMP
a. UTP -> UDP + Pi
b. UDP -> dUDP
i. catalyzed by ribonucleotide reductase
c. dUDP + ATP -> dUTP + ADP
d. dUTP -> dUMP + PPi (-> 2Pi)
e. dUMP -> dTMP (through methylation by thymidylate synthase)
2. via d-CDP
a. CTP -> CDP + Pi
b. CDP -> dCDP
i. catalyzed by ribonucleotide reductase
c. dCDP -> dUMP + NH4+ + Pi (through deaminase and phosphatase)

Front 172

thymidylate synthase

Back 172

does methylation of dUMP into dTMP, uses methylene-THF and adds CH3 to dUMP, this CH3 is reduced and methylene THF is itself oxidized to dihydrofolate, THF is remade when DHF is reduced to THF by dihydrofolate reductase (uses NADPH and gives off NADP+), this is inhibited by methotrexate (MTX, acts as an analogue to DHF)

Front 173

cancer patients

Back 173

block thymine biosynthesis in cancer patient, blocks the reformation of THF, why chemotherapy is so crazy, hair and gut regenerate fast and affected by these things

Front 174

relationship between purines and pyrimidines

Back 174

PRPP can turn on both purine and pyrimidine synthesis, ATP can also stimulate pyrimidine synthesis

Front 175

regulation of ribonucleotide reductase

Back 175

acts as a switch, on when [ATP] is high, off when [dATP] is high, on form has INC binding affinity for ribonucleotide reductase for CDP and UDP, dTTP is made from both dCDP and dUDP, dTTP inhibits both CDP and UDP to deoxy forms and stimulates GDP to dGDP form, dGTP is then made and inhibits GDP to dGPD and stimulates ADP to dADP, dATP is made and turns the system off

Front 176

degradation of DNA and RNA

Back 176

1. DNA and RNA -> nucleotides
a. via nucleases and phosphodiesterases
2. nucleotides (monophosphates) -> nucleosides + Pi
a. via phosphatase
3. nucleosides + Pi -> base + sugar
a. via phosphorylase
4. sugar -> ribose-1-P or dexoy-R

Front 177

salvage of the degradation of DNA and RNA

Back 177

1. sugar-ribose-1-P can be salvaged as ribose-5-P through a phosphoribo mutase, ribose-5-P can then enter HMPS (consume sugar) or PRPP (salvage them and reuse them)
2. base-handled differently for purines and pyrimidines
3. nucleosides-not always reused, can but not always
4. nucleotides-reused

Front 178

pyrimidine salvage

Back 178

is readily done, add PRPP to the pyrimidines taken in (O.A., Cyto, Uracil) and form (OMP, CMP, UMP), PRPP added to ring after ring is formed, thymine is not salvaged, if thymine and PRPP were added together would get ribose-thymine but ribonucleotide reductase would not act on this substrate

Front 179

purine salvage

Back 179

must use different enzymes for A and G and HX, PRPP is added to A to make AMP catalyzed by adenine-phosphoribosyl transferase (A-PRT), PRPP is added to G or HX to form GMP or IMP and this is catalyzed by G/HX-PRT, this is also catalyzed by guanine-hypoxanthine phosphoribosyl transferase

Front 180

cytosine (and uracil) degradation

Back 180

1. cytosine loses NH4+ and O2 is added to form uracil
2. uracil undergoes reduction with NAD(P)H to form dihydro-Uracil
3. dihydro-uracil undergoes cleavage to form ureidopropionate (AKA carbamoyl-beta-alanine)
4. carbamoyl-beta-alanine loses NH4+ and CO2 to form beta alanine
5. beta alanine can be turned into acetyl-CoA

Front 181

uracil synthesis

Back 181

OMP -> UMP + CO2
catalyzed by orotidylate decarboxylase, UMP is used to inhibit CPS-II can then be phosphorylated by two ATPs to form UTP,

Front 182

CTP synthesis

Back 182

UTP + ATP + Gln -> CTP + Glu + ADP + Pi
catalyzed by cytidylate synthetase

Front 183

notes for pyrimidine synthesis

Back 183

is completely a linear a pathway and the sugar handle is added after the ring is formed

Front 184

thymine biosynthesis

Back 184

ribose needs to be converted to deoxyribose before uracil nucleotide can be methylated to thymine

Front 185

ribonucleotide reductase

Back 185

Ribose + thioredoxin (has 2 reduced cys) -> 2’-deoxyribose + oxidized form of thioredoxin
catalyzed by ribonucleotide reducatse, requires diphosphate level of nucleotide substrate (not tri- or mono-), must then recycle to get back reduced thioredoxin, use flavoprotein and thioredoxin reductase and oxidize FADH2 to FAD, must then recycle to get back FADH2, use the flavoprotein again and oxidize NADPH to NADP+ to get back FADH2, must the regenerate NADPH and that comes from HMPS and malic enzyme

Front 186

formation of dTMP

Back 186

1. via d-UMP
a. UTP -> UDP + Pi
b. UDP -> dUDP
i. catalyzed by ribonucleotide reductase
c. dUDP + ATP -> dUTP + ADP
d. dUTP -> dUMP + PPi (-> 2Pi)
e. dUMP -> dTMP (through methylation by thymidylate synthase)
2. via d-CDP
a. CTP -> CDP + Pi
b. CDP -> dCDP
i. catalyzed by ribonucleotide reductase
c. dCDP -> dUMP + NH4+ + Pi (through deaminase and phosphatase)

Front 187

thymidylate synthase

Back 187

does methylation of dUMP into dTMP, uses methylene-THF and adds CH3 to dUMP, this CH3 is reduced and methylene THF is itself oxidized to dihydrofolate, THF is remade when DHF is reduced to THF by dihydrofolate reductase (uses NADPH and gives off NADP+), this is inhibited by methotrexate (MTX, acts as an analogue to DHF)

Front 188

cancer patients

Back 188

block thymine biosynthesis in cancer patient, blocks the reformation of THF, why chemotherapy is so crazy, hair and gut regenerate fast and affected by these things

Front 189

relationship between purines and pyrimidines

Back 189

PRPP can turn on both purine and pyrimidine synthesis, ATP can also stimulate pyrimidine synthesis

Front 190

regulation of ribonucleotide reductase

Back 190

acts as a switch, on when [ATP] is high, [dATP] is high, on form has INC binding affinity for ribonucleotide reductase for CDP and UDP, dTTP is made from both dCDP and dUDP, dTTP inhibits both CDP and UDP to deoxy forms and stimulates GDP to dGDP form, dGTP is then made and inhibits GDP to dGPD and stimulates ADP to dADP, dATP is made and turns the system off

Front 191

degradation of DNA and RNA

Back 191

1. DNA and RNA -> nucleotides
a. via nucleases and phosphodiesterases
2. nucleotides (monophosphates) -> nucleosides + Pi
a. via phosphatase
3. nucleosides + Pi -> base + sugar
a. via phosphorylase
4. sugar -> ribose-1-P or dexoy-R

Front 192

salvage of the degradation of DNA and RNA

Back 192

1. sugar-ribose-1-P can be salvaged as ribose-5-P through a phosphoribo mutase, ribose-5-P can then enter HMPS (consume sugar) or PRPP (salvage them and reuse them)
2. base-handled differently for purines and pyrimidines
3. nucleosides-not always reused, can but not always
4. nucleotides-reused

Front 193

pyrimidine salvage

Back 193

is readily done, add PRPP to the pyrimidines taken in (O.A., Cyto, Uracil) and form (OMP, CMP, UMP), PRPP added to ring after ring is formed, thymine is not salvaged, if thymine and PRPP were added together would get ribose-thymine but ribonucleotide reductase would not act on this substrate

Front 194

purine salvage

Back 194

must use different enzymes for A and G and HX, PRPP is added to A to make AMP catalyzed by adenine-phosphoribosyl transferase (A-PRT), PRPP is added to G or HX to form GMP or IMP and this is catalyzed by G/HX-PRT, this is also catalyzed by guanine-hypoxanthine phosphoribosyl transferase

Front 195

cytosine (and uracil) degradation

Back 195

1. cytosine loses NH4+ and O2 is added to form uracil
2. uracil undergoes reduction with NAD(P)H to form dihydro-Uracil
3. dihydro-uracil undergoes cleavage to form ureidopropionate (AKA carbamoyl-beta-alanine)
4. carbamoyl-beta-alanine loses NH4+ and CO2 to form beta alanine
5. beta alanine can be turned into acetyl-CoA

Front 196

thymine degradation

Back 196

thymine -> di-hydrothymine -> beta-amino isobutyric acid -> lose NH4+ and CO2 (carbomyl is lost), then lose another NH4+ to form methyl malonyl CoA, methyl malonyl CoA is formed into succinyl-CoA with B12 mutase

Front 197

adenosine degradation

Back 197

1. adenosine -> inosine + NH4+
a. catalyzed by adenosine deaminase (A.D.A.)
2. inosine + Pi -> hypoxanthine + R-1-P
3. hypoxanthine + O2 -> xanthine + H2O2
a. catalyzed by xanthine oxidase (X.O.)
b. H2O2 is recycled to O2 via catalase
4. xanthine + O2 -> uric acid + H2O2
a. catalyzed by xanthine oxidase (X.O.)
b. H2O2 is recycled to O2 via catalase
5. uric acid is excreted

Front 198

guanosine degradation

Back 198

1. guanosine + Pi -> guanine + R-1-P
a. catalyzed by purine nucleoside phosphorylase
2. guanine + H2O -> xanthine + NH4+
a. catalyzed by guanase
3. xanthine -> uric acid
a. catalyzed by xanthine oxidase
4. uric acid is excreted

Front 199

Gout

Back 199

uric acid (less soluble) <-> enol <-> urate (more soluble), the uric acid that is less soluble will prevail at low pH and will precipitate in tissues, forms needle-like crystals form in synovial fluid leading to gout