Block 1: Biochemistry Part 2

Front 1

Tetrahydrofolate (THF)

Back 1

Synth in bacteria
Reduced form of folate
Transfers single carbons

Front 2

S-Adenosyl Methionine

Back 2

Synth from ATP+methionine
Transfers methyl groups
After transfer of methyl group = SAhomocystine ➔ homocystine

Front 3

Biotin

Back 3

Transfers CO₂

Front 4

Tetrahydrobiopterin

Back 4

Involved in oxidation rxns (tyrosine synthesis)

Front 5

Pyridoxal Phosphate (PLP)

Back 5

Cofactor in transaminase rxn
Coenzyme from of Vit B₆
Holds nitrogen

Front 6

TCA Intermediates and AA synthesis

Back 6

Front 7

Glutamate Synth

Back 7

Ammonia drives rxn, occurs readily in liver (⬆ammonia levels)

Front 8

Glutamine Synth

Back 8

Glu does not transport across cell membranes
Gln does ➔ allows for trans. of detoxified from of ammonia

Front 9

Glucose-Glutamine Cycle

Back 9

Front 10

Alanine Synth

Back 10

Transaminases are highly reversible, require PLP as cofactor

Front 11

Glucose-Alanine Cycle

Back 11

Front 12

Aspartate Synth

Back 12

Front 13

Asparagine Synth

Back 13

Essential AA
Not glycosylated

Front 14

Serine Synth

Back 14

Generates NADH

Front 15

Glycine Synth

Back 15

Front 16

Methionine Synth

Back 16

Front 17

Cysteine Synth

Back 17

Just know red and homocysteine

Front 18

Tyrosine Synth

Back 18

Just know red

Front 19

Degradation of Endogenous Proteins

Back 19

Trypsin/chymotrypsin in sm. intestine
Ubiquitin
Binds lys-residues
Greater chain = higher signal for degredation
N-Term destab = R or L = fast ubiquination
N-Term stab = M or P = slow ubiquination
PEST sequences

Front 20

AA ➔ Pyruvate

Back 20

Ala, Cys, Gly, Ser, Thr, Trp

Glucogenic = can resynth glucose
Pyruvate converted to
OAA
Acetyl-CoA ➔ Citrate or Ketone bodies

Mutations
Glycine Transaminase = Oxaluria Type 1 (Glyoxylate ➔ Gly)
Glycine Cleavage EZ = non-ketotic hyperglycinemia
Cystathione Synthase = homocystineuria

Front 21

AA ➔ Acetyl-CoA

Back 21

Iso, Leu, Thr, Tyr, Trp, Phe, Lys

Ketogenic = can't resynth glucose
Acteyl-CoA or Acetoacyl-CoA

Mutations
Phenylalanine hydroxylase = PKU
Tyrosine aminotransferase = Tyrosinemia II
Homogentisate oxidase = homogentisic acid intermed., Alkaptonuria
Fumarylacetoacetate hydroxylase = Fumarylacetoacetate intermediate, Tyrosinemia I

Front 22

AA ➔ α-ketoglutarate

Back 22

Arg, Gln, His, Pro ➔ Glu

Glucogenic = can resynth glucose
α-ketoglutarate

Mutations
Folate Deficincy = Forminic glutamic acid accumulation
Histidinase deficiency = Histidinemia

Front 23

AA ➔ OAA

Back 23

N, D

Front 24

Branched Chain AA Degredation

Back 24

Front 25

AA ➔ Succinyl-CoA

Back 25

Met, Thr, Val, Iso

Glucogenic = can resynth glucose
Succinyl-CoA

Mutations
Methylmalonyl CoA Mutase = Methylmalonic aciduria

Front 26

Location of AA Metabolism

Back 26

Gln and Glu metabolized in intestinal mucosal cells
Most others go to liver
Branched chain AA leave liver and go to muscle for transamination and returned to liver

Fasting
Ala goes to liver for gluconeo
Glu goes to kidneys and intestines

Front 27

First Step in Urea Cycle

Back 27

Front 28

Urea Cycle

Back 28

Know Ornithine/Citrullene

2 Nitrogen groups picked up
1 from carbamoyl phosphate
1 from aspartate

Failure
Hyperammonemia and encephalopathy (liver cirrhosis can also lead to hyperammonemia ➔ CNS disorder)
⬆ Ammonia = derails TCA, removes α-KG via conversion to glutamine

Front 29

Urea

Back 29

Blood Urea Nitrogen (BUN), rises sharply in renal failure
Urease cleaves urea ➔ making urine basic ➔ ppt of NH₄MgPO₄ ➔ kidney stones

Front 30

Reaction Free Energy

Back 30

If ∆H > 0, reaction is spontaneous (∆G < 0) only if ∆S > 0
If ∆H < 0, a reaction can be spontaneous (∆G < 0) even if ∆S < 0

Front 31

High energy compounds

Back 31

NADH oxidation (to NAD+) -15 kcal/mole
FADH2 oxidation (to FADH+) -15 kcal/mole

Front 32

ETC

Back 32

Go from ⬇ reduction potential to ⬆ reduction potential as you progress down complexes, water is final electron acceptor (high reduction potential, this makes it more favorable)

Front 33

NAD

Back 33

Gives 2e⁻ at once

Front 34

Flavoproteins

Back 34

FAD = ADP
FMN = Ribose

Both conjugated to protein
Gives 1 or 2e⁻

Front 35

Quinones

Back 35

Gives 1 or 2e⁻ , freely diffusible w/in inner membrane bilayer

Front 36

Cytochromes

Back 36

Have heme cofactors

Front 37

Complex I

Back 37

NADH dehydrogenase
6 Fe-S centers
FMN-containing flavoprotein
4 Protons pumped
Electrons = NADH to ubiquinone

Front 38

Complex II

Back 38

Succinate dehydrogenase
Contains heme b (cyt b), FAD/FMN
No protons pumped out
Electrons = succinate to ubiquinone

Front 39

Complex III

Back 39

Cytochrome C oxidoreductase
2 cytochrome b in middle of membrane (cavern, where ubiquinone moves_
1 cytochrome c soluble
4 protons pumped out
Electrons = ubiquinone to cyto c

Front 40

Complex IV

Back 40

Cytochrome oxidase
Subunit 1 = 2 Cu w/ SH
Subunit 2 = 2 heme groups and Cu

Front 41

ATP Synthase

Back 41

Alkaline pH and (-) charge inside the matrix create proton motive force that drives ATP synth.

F₀ base turning driven by proton gradient and causes conformation changes in F₁
F₁ lollipop head, inside matrix, binds ADP + P, forces them together and kicks ATP out

Front 42

ATP and H⁺ transport

Back 42

Adenine Nucleotide Translocase (antiporter) = ADP transported into matrix, ATP transported out

Phosphate Translocase (symporter) = mono hydrogen phosphate and H⁺ transported into matrix

Front 43

Thermogenin

Back 43

Uncouples ox. phos. by transporting protons into matrix, releases heat

Found in brown adipose tissue

Front 44

Purine synth

Back 44

PRPP = starting substrate, how ribose is incorporated into nucleotides, 2 ATP required to convert (Ribose-5-P to PRPP)

Folic acid deficiency is a major problem for this pathway
No biotin used in this pathway for carboxylation from CO₂

Glutamine-PRPP amidotransferase
PRPP + glutamine + H₂O = substrate + glutamate + PP
Regulatory Step
(+) = PRPP
(-) = NTP, NDP, NMP

End product is IMP

Front 45

AMP/GMP from IMP (2 ways to inhibit)

Back 45

First way (see img/below): co-rxn regulation
GTP to make AMP ➔ more AMP made, GMP formation rxn is faster now
ATP to make GMP ➔ more GMP made, AMP formation rxn is faster

Second way:
GMP/AMP feedback and inhibit their synth

Salvage
GMP/AMP ➔ Xanthine which is converted (xanthine oxidase) into uric acid

Front 46

Pyrimidine synth

Back 46

1 N = glutamine
1 N, 3 C = Asp
1 C = CO₂ via carbamoyl phosphate

Front 47

Deoxyribose synth

Back 47

catalyzed by Ribonucleotide reductase
Highly regulated/finely tuned = many different binding sites for nucleotides (inhibit rxn)

Front 48

Thymidylate synth

Back 48

Know Thymidylate synthase and DHF reductase

Salvage
Thymine ➔ methylmalonyl semialdehyde which is converted (Vit B₁₂ + mutase) into succinyl-CoA

Front 49

Cytidylate synth

Back 49

Salvage
Cytosine degrades into uracil ➔ acetyl-SCoA