Protein Biochem - eisenmesser

Question 1

Ketogenic aa

Answer 1

Leu

Lys

Question 2

Both ketogenic and glucogenic aa

Answer 2

Phe
Tyr
Iso
Trp

“Pee TIP”

Question 3

Post translational mod of which two proteins strengthen and modify Collagen? Why do we care?

Answer 3

4-hydroxyproline (Hyp)
- Interstrand H bonding

5-hydroxylysine (Hyl)

• interstrand X-links between Lys & Hyl
• forms covalent interstand X- links

*collagen is the most abundant protein in body

Question 4

Both Prolyl hydoxylase and Lysel hydroxylase require what?

Answer 4

Ascorbate (VIt C) in order to convert Pro to Hyp and Lys to Hyl

(without it

Question 5

Sx of scurvy

Answer 5

Reduced strength of collagen fibrils

Reduced vascular endothelium

→ swollen gums, bruising, anemia

Question 6

gamma-carboxyglutamate (Gla) fxn

• what does it do
• what is it dependent on?

Answer 6

transmembrane prot that converts Glu to Gla by chelating Ca2+

Vit K dependent
Used by Prothrombin to target membranes

Question 7

Which one degrades endogenous protein, and which extracellular prot?
Ubiquination, lysosomal degradation

Answer 7

Ubiquination: endogenous
- targets enzymes (E1-E3) to proteins (lysine) using ATP and direct them into proteosome

Lysosome: extracellular
- taken in by endocytosis to mix with digestive enzymes

Question 8

Enzymatic degradation proteins in:

• Stomach
• intestine

Answer 8

Stomach
- Pepsin (peppy chief)

Intestine

• Trypsin
• Chymotrypsin
• Carboxypeptidase-A + B

Question 9

How are these enzymes activated from zymogens

Stomach
- Pepsin (peppy chief)

Intestine

• Trypsin
• Chymotrypsin
• Carboxypeptidase-A
• Carboxypeptidase-B

Answer 9

Stomach
- Pepsinogen → Pepsin (peppy chief) (via HCl)

Intestine

• Trypsin (via enteropeptidase)
• Chymotrypsin (via trypsin)
• Carboxypeptidase-A + B (via enteropeptidase)

*note that Trypsin can activate all of the E in intestine

Question 10

Which one of these are aspartic proteases, serine proteases, and metallocarboxypeptidases

• Carboxypeptidase-A+B
• Trypsin
• Chymotrypsin
• Pepsin (peppy chief)

Answer 10

Aspartic: (hydrolyzes N term)
- pepsin

Serine: (hydrolyzes C term)
- Trypsin + chymotrypsin

Metallocarboxypeptidases
(hydrolyzes C term)
- Carboxypeptidase A+B

Question 11

Aminotransferases catalyze what?
Major goal?
Where?

Answer 11

Rxn of an a-keto acid and an amino acid to another a-keto acid and amino acid

• Reversible Keq=1
• Major goal: make Asp, NH3 for Urea cycle
• Mostly in cytosol (liver, kidney, intestine, muscle)

Question 12

Transamination feeds what?

Answer 12

The urea cycle

- Major goal: make Asp, NH3 for Urea cycle

Question 13

What does PLP form with the aminotransferase?

Answer 13

Forms “Schiff base” (a covalent linkage) with the aminotransferase,

Question 14

Progressive hyperammonemia can cause

Answer 14

cerebral edema, coma, and death

Question 15

Alanine + a-ketoglutarate → ?

aspartate + a-ketoglutarate → ?

Answer 15

ALT: pyruvate + glutamate

AST: oxaloacetate + glutamate

Question 16

When you see ORNT1, think:

Answer 16

Ornithine INto mitochondria matrix

Citrulline OUT into cytosol

Question 17

Control point for protein catabolism

Answer 17

1. Directionality of ALT + AST regulated by products + substrates
2. Carbamoyl phosphate synthetase I
   - required activator: N-acetylglutamate
3. Glutamate dehydrogenase
   - regulates NH3 transport
   - depends on [ ] of Glu, a-ketoglut, NH3

Question 18

Ammonia is toxic, so how do you transfer it from peripheral tissues to kidneys and liver?

Answer 18

Glutamine is used to hold 2 Ns

Glutamate (1 N) + NH3 + ATP + (Gln synthetase) → glutamine (2 N)

Question 19

What is produced for the transport of ammonia in:
Peripheral tissue:
Muscle:
Liver:

Answer 19

Peripheral tissue: Gln
Muscle: Ala
Liver: Urea

Question 20

What role does the kidney play in the transport of ammonia?

Answer 20

Removes Urea

Removes Ammonia from Glutamate

Question 21

What is significant about Glu dehydrogenase?

Answer 21

It is involved in the transport of ammonia

1. converts Glutamate → a-ketoglutarate
   - provides free NH3 for Urea cycle
   - pee out NH3 (kidney)
2. Converts a-ketoglutarate + NH3 → Glutamate
   - Glutamate can be converted to Ala for transport from muscle to liver
   - Glutamaet can be converted to Glutamine for transport from periph tissue to liver

Question 22

Activator vs inactivator of glutamate dehydrogenase

• ATP
• ADP
• GTP
• GDP

Answer 22

Inactivator
- ATP + GTP

Activator
- ADP + GDP

(mutation in ATP/GTP binding site → hyperinsulinism-hyperammonemia syndrome: cant shut off NH3 maker)

Question 23

NO is derived from what?

Answer 23

Arginine via NO synthase

Arginine + NO synthase → Citrulline + NO

NO is a NT

Question 24

Aspartate transamination yields _______. It can be converted to _____ in the krebs cycle TCA.

Answer 24

oxaloacetate, fumarate

aspartate and asparagine yields oxaloacetate

Question 25

Asparagine yields ______ after hydrolysis catalyzed by the enzyme _____.

Answer 25

Asparagine → aspartate via asparaginase aspartate can be converted to oxaloacetate just like asparagine

Question 26

MSUD - what Enz is affected? Deficiency or lack of? This leads to build up of?

Answer 26

Deficiency of BCKDH (branched chain a-keto acid dehydrogenase) Build up of branched chain aa Val, Ile, Leu

Question 27

Rank most active to less active Tyrosine T4 T3

Answer 27

T3 > Tyrosine > T4 | T4 is made from tyrosine. T4 is a prohormone, so not very active

Question 28

Order that they are made Tyrosine T4 T3

Answer 28

Tyrosine → T4 → T3

Question 29

How is T3 and T4 made?

Answer 29

Thyroglobulin (TG) binds to I2 and gets iodinated. Then it undergoes protealysis to T3, T4 Thyroxin binding protein (TBP) carries it to blood

Question 30

TSH

Answer 30

``` Stimulates Iodide (I-) uptake Stimulates release of T4, T3 ```

Question 31

Thyroid peroxidase

Answer 31

Oxidizes Iodide (I-) to (I2)

Question 32

Thyroglobulin (TG)

Answer 32

Contains Tyr residues iodinated to form T4, T3

Question 33

Thyroxin binding globulin (TBG)

Answer 33

Transports T4, T3

Question 34

How does lead lead to anemia?

Answer 34

Can replace Zn in ALA dehydratase - prevent production of porphobilinogen Can replace Fe2+ in ferrochelatase - prevents heme production

Question 35

What enzyme is typically low in premature infants leading to jaundice babies? What other defects also involve this enzyme?

Answer 35

Bilirubin glucuronyl transferase - use flourescent light to convert bilirubin to more polar products, allowing removal - remember that this Enz allows unconj bilirubin to be converted to bilirubin, which will eventually become conj bili 1. Crigler-Naijar syndrome 2. Gilbert syndrome

Question 36

Which is essential, which is non essential? Methionine, cysteine.

Answer 36

Methionine is essential - cysteine can be made from Met (non essential) *noet: cysteine can form disulfide crosslinks with other cysteines to form CYSTINE.

Question 37

1st step of Met degradation

Answer 37

Methionine → SAM via SAM synthase + ATP SAM has an activated sulfur SAM is also known as adoMet

Question 38

How does methionine degrade and form cysteine?

Answer 38

Met + Ser = Cys Met → SAM → SAH → Homocysteine (+Ser) → Cystathionine → Cysteine (these rxns involve addn of ATP, demethylation, and removal of adenosine)

Question 39

How do you regenerate Methionine

Answer 39

Need TWO coenzymes: 1. THF 2. Vit B12 - methyl group is transferred from THF to B12 to homocysteine

Question 40

Which Vit are probably deficient if you have a build up of homocysteine?

Answer 40

B6 and B12

Question 41

How is cysteine synth achieved from Homocysteine and serine?

Answer 41

Via cystathionine B-synthase (CBS) + PLP | PLP is a derivative of Vit B6 - it is also needed to convert cystathionine to cysteine.

Question 42

Hyperhomocysteinemia levels | - tx

Answer 42

(Possible MTHFR enz defective and cant convert Homocysteine to methionine) Low levels folate Low levels B6, B12 - cysteine is now an essential vit tx: folate, B6, B12

Question 43

Homocystinuria defect | - tx

Answer 43

defect in cystathionine B Synthase (CBS) - retardation, osteoporosis, vascular disease - cysteine is now essential (just like hyperhomo) Tx: Vit B6, to force CBS activity

Question 44

Cysteinuria defect | - tx

Answer 44

defective transporter of cysteine (COAL) - crystalization in kidneys (stones) Tx: acetazolamide - makes cysteine more soluble

Question 45

Is homocysteine good?

Answer 45

No! IS bad! 1. Vascular disease 2. Impaired wound healing 3. Correlated to cancer (cervical)

Question 46

SAM actions

Answer 46

1. Methylation via SAM dependent enzymes 2. Epigenetics (host defense) 3. Cancer (meth/demeth) 4. High levels of Met and SAM critical in maternal diet 5. treat depression

Question 47

THF is produced from Vit B9 (Folic acid) by what enzyme? | What drug blocks this enzyme?

Answer 47

``` Dihydrofolate reductase (DHER) - blocked by methotrexate ``` Methotrexate basically prevents production of THF

Question 48

Why is Glutathione (GSH) important?

Answer 48

1. Thiol (glutaTHIO) acts as a redox buffer to keep proteins in reduced form and regulate activity 2. cofactor for other enzymes 3. Protection against ROS (reduct H2O2)

Question 49

Glutathione (GSH) is it active in unfolded (reduced) state or folded state?

Answer 49

Active in folded state | - disulfide bonds are cross linked and ready fo action

Question 50

Example of how GSH acts as a redox buffer to keep proteins in reduced form and regulate activity

Answer 50

Keeps Fe2+ in ferrous state, capable of binding O2. | Fe3+ cannot bind O2

Question 51

Why is Trp such an important aa?

Answer 51

- Trp can be metabolized to Pyruvate or acetyl-CoA - Trp (with BH4 cofactor) make: 1. Serotonin 2. Melatonin 3. Niacin (critical cofactor for NAD)

Question 52

Why are MAO inhibitors so helpful?

Answer 52

They block deamination like cray. Prevent the breakdown of DA.