Chapter 23: Protein Turnover And Amino Acid Metabolism

Front 1

amino acids are building blocks of...

Back 1

proteins and nitrogenous compounds (such as nucleotide bases)

Front 2

9 essential amino acids

Back 2

histidine
isoleucine
leucine
lysine
methionine
phenylalanine
threonine
tryptophan
valine
(usually aromatic, branched chain)

Front 3

digestion of dietary protein

Back 3

-stomach acid denatures protein makes peptide bonds more accessible to proteolytic enzymes in lumen
-aminopeptidases and peptidases (in intestinal cell) further break down proteins to amino acids

Front 4

proteolytic enzymes
(where are they made, where do they do their job?)

Back 4

-made in pancreas and delivered to duodenum for digesting proteins
-synthesized as zymogens (activated by proteolytic cleavage)

Front 5

digestive peptidases (2 kinds)

Back 5

endopeptidases hydrolyze peptide bonds within chains
exopeptidases (aminopeptidases and carboxypeptidases) hydrolyze terminal peptide bonds

Front 6

ubiquitin
(also, how is it linked to protein?)

Back 6

-marks proteins for destruction
-small protein present in all eukaryotic cells
-covalently linked through isopeptide bond to lysine residues of protein targeted for destruction
-4 ubiquitin on a protein seals its fate

Front 7

ubiquitin conjugation to a protein

Back 7

E1 (ubiquitin activating enzyme): adenylates and activates Ub using ATP then transfers Ub to one of its own Cys residues
E2 (ubiquitin conjugating enzyme): Ub is shuttled from sulfhydryl on E1 to sulfhydryl group on E2
E3 (Ub protein ligase) catalyzes transfer of activated Ub from E2 to target protein

Front 8

what determines half-life of a protein (when Ub targets it)?

Back 8

amino terminal--there are stabilizing a.a.'s and destabilizing a.a.'s. Sequences containing Pro, Glu, Ser, and Thr mark cell-cycle proteins for destruction

Front 9

proteosome

Back 9

-multi subunit, interior catalytic site
-ATP driven unfolding of substrate
-catalytic core destroys Ub-tagged proteins, but spares ubiquitin
-degrades substrates in processive manner until short peptides are produced

Front 10

ubiquitin and Parkinson's

Back 10

proteins that are not degraded due to defective E3s may aggregate, contributing to juvenile or early-onset Parkinsons

Front 11

Angelman syndrome and ubiquitin

Back 11

a neurological disease--mental retardation, absence of speech, uncoordination, hyperactivity---defective E3

Front 12

HPV and ubiquitin

Back 12

HPV promotes tumor formation--activates E3 which destroys tumor suppressor p53 and proteins that regulate DNA repair--leads to tumor formation

Front 13

degradation of amino acids
(where does it occur, why does it occur, what does it consist of?)

Back 13

occurs in muscle and liver
excess amino acids can't be stored
consists of removal of N group and metabolism of C skeleton

Front 14

transamination
(also what is the coenzyme and what is key in the reaction)

Back 14

common step in amino acid degradation
aminotransferases catalyze transfer of alpha-amino group from donor amino acid to acceptor alpha-keto group (usually alpha-ketoglutarate)
coenzyme=pyridoxal phosphate
schiff base formation is key

Front 15

2 amino acids that can be directly converted to NH4+

Back 15

serine and threonine are converted by dehydratases

Front 16

2 important transamination reactions

Back 16

aspartate + alpha-ketoglutarate ---> OAA + glutamate
alanine + alpha-ketoglutarate ---> pyruvate + glutamate

Front 17

liberation of ammonia from glutamate

Back 17

glutamate dehydrogenase catalyzes an oxidataive deamination that converts the N atom in glutamate into NH4+
enzyme is located in mitochondria (sequestering ammonia for elimination)
reduces NAD+ or NADP+

Front 18

ammoniotelic organisms

Back 18

aquatic vertebrates and invertebrates release N as NH4+ into environment

Front 19

ureotelic organisms

Back 19

terrestrial amphibia and mammals excrete NH4+ as urea

Front 20

uricotelic organisms

Back 20

birds and reptiles secrete N as pure uric acid

Front 21

to transport ammonia in blood, it is conjugated to...

Back 21

pyruvate so Alanine is transported

Front 22

step 1 of the urea cycle

Back 22

synthesis of carbamoyl phosphate from bicarbonate
enzyme: carbamoyl phosphate synthetase (doesn't use biotin)
uses 2 ATP, brings NH4+ into cycle

Front 23

step 2 of urea cycle

Back 23

carbamoyl phosphate enters cycle in a reaction with ornithine (ornithine is in mitochondria, but rest of cycle occurs in cytoplasm)

Front 24

where do the 2 amino groups on urea come from?

Back 24

aspartate and carbamoyl phosphate

Front 25

arginosuccinate of urea cycle becomes what in reaction using arginosuccinase?

Back 25

arginine (contains both N's), fumarate (C-skeleton from Asp)

Front 26

the splitting of arginine in the urea cycle results in...
(also what enzyme is used)

Back 26

ornithine and urea (freed in mitochondria)
arginase=enzyme

Front 27

where does the C in urea come from?

Back 27

HCO3

Front 28

what can fumarate be used for?

Back 28

used to regenerate aspartate via malate and oxaloacetate or can go into gluconeogenesis

Front 29

arginosuccinase deficiency

Back 29

blocks cleavage of arginosuccinate, so arginosuccinate is excreted and arginine is not replenished
treatment: reduce protein intake and supply excess arg

Front 30

carbamoyl phosphate synthetase deficiency

Back 30

synthesis of carbamoyl phosphate is blocked--NH4+ can't enter urea cycle and excess N accumulates in a.a.'s
Gly and Glu are elevated

Front 31

ornithine transcarbamoylase deficiency

Back 31

synthesis of citrulline is blocked
NH4+ can't enter urea cycle
excess N accumulates in a.a.'s
Gly and Glu are elevated
(similar to carbamoyl phosphate synthetase deficiency)

Front 32

how are carbamoyl phosphate synthetase deficiency and ornithine transcarbamoylase deficiency treated?

Back 32

activation of latent pathways
supply unnatural substrates that are metabolized and transaminated by existing enzymatic pathways and excreted
can trick enzyme into taking benzoic acid or phenylacetate

Front 33

2 fates of carbon atoms from degraded amino acids

Back 33

14 gluconeogenic amino acids can be used in net synthesis of glucose
ketogenic amino acids can give rise to ketone bodies

Front 34

how do C skeletons of amino acids enter TCA cycle?

Back 34

C skeletons of gluconeogenic amino acids enter as pyruvate or TCA cycle intermediates
C skeletons of ketogenic amino acids enter as acetyl CoA or acetoacetyl CoA

Front 35

pyruvate is point of entry into TCA cycle for what amino acids?

Back 35

Ala, Ser, Cys, Thr (also Glycine can become Ser and tryptophan side chain is identical to Ala)

Front 36

OAA is point of entry into TCA cycle for what amino acids?

Back 36

Asp and Asn

Front 37

alpha-ketoglutarate is point of entry into TCA cycle of which amino acids?

Back 37

5-C amino acids
Glu, Pro, Arg, His

Front 38

what amino acids yield acetyl CoA, acetoacetate or propionyl CoA? by what reactions?

Back 38

branched-chain amino acids--Leu, Iso, Val
via transamination and oxidations

Front 39

propionyl CoA is an intermediate in the metabolism of what amino acid?

Back 39

methionine (propionyl CoA can then enter intermediary metabolism via succinyl CoA)

Front 40

tetrahydrobiopterin
(also give an example of a reaction)

Back 40

important electron carrier in hydroxylation reactions
(phenylalanine--->tyrosine)

Front 41

aromatic amino acids yield

Back 41

fumarate and acetoacetate

Front 42

dioxygenases

Back 42

catalyze a reaction in which both atoms of O from O2 are incorporated into product

Front 43

tyr metabolism requires what kind of reactions?

Back 43

monoxygenase and dioxygenase

Front 44

cleavages of aromatic rings are catalyzed by...

Back 44

dioxygenases

Front 45

phenylketonuria

Back 45

deficiency of phenylalanine hydroxylase
controlled by low phe diet--eliminate high-protein food
substitute with synthetic formula, supplement tyr

Front 46

aspartame

Back 46

has phe in it (sweetener)

Front 47

albinism

Back 47

cannot oxidise tyrosine so can't make pigment