1st three lectures - Eisenmesser

Question 1

Name the ketogenic amino acids:

Answer 1

Leucine (Leu)

Lysine (Lys)

Question 2

What two post-translationally modified amino acids are used in collagen?

Answer 2

Hydroxyproline (Hyp)

Hydroxylysine (Hyl)

Question 3

What post-translationally modified amino acid is used in prothrombin?

Answer 3

Gamma-carboxyglutamate (Gla)

Question 4

How does hydroxyproline contribute to the structure of collagen?

Answer 4

Formation of interstrand H-bonds

Question 5

How does hydroxylysine contribute to the structure of collagen?

Answer 5

Formation of covalent linkages between hydroxylysine and lysine. (Hyl-lys)

Question 6

What enzymes are responsible for forming the modified amino acids incorporated into collagen? Name both, with starting and end products.

What is needed as a cofactor for this reaction to proceed?

Answer 6

Lysine–> hydroxylysine = Lysyl hydroxylase
Proline–>hydroxyproline = Prolyl hydroxylase

Vitamin C.

Question 7

Fill in the enzyme. What cofactor is required?

Glu —-_____—-> Gla

Answer 7

Glutamate —> gamma-carboxyglutamate (Gla)

Enzyme–> Gamma glutamyl carboxylase

**Vitamin K is required. (Hence the prothrombin time/vitamin K deficiency. Prothrombin uses Gla to target membranes)

Question 8

____ + _____ —ALT—> ____+_____

Regulation?

Answer 8

Alanine + alpha-ketoglutarate—> pyruvate + glutamate

**Regulated by relative concentrations of substrate/product (Thus regulating entry of NH3 into the urea cycle)

Question 9

____ + _____ —AST—> ____+_____

Regulation?

Answer 9

Aspartate + alpha-ketoglutarate—> OAA + glutamate

**Regulated by relative concentrations of substrate/product
Thus regulating entry of NH3 into the urea cycle

Question 10

What happens to glutamate after nitrogen is added by ALT?

Answer 10

The NH3 group is removed by glutamine aminotransferase. It then enters the urea cycle as ammonia.

OR

THe reverse AST reaction is performed, creating aspartate (with the nitrogen attachced). Aspartate then enters the urea cycle.

Question 11

Transamination reactions require what as a cofactor?

Answer 11

PLP. This is a B6 derivative. (All transaminases, eg ALT/AST)

PLP “holds” the amino group during its transfer.

Question 12

Ammonia is toxic, so _____ is used to transport it from the peripheral tissues to the ___ and ___.

Answer 12

glutamine

kidneys, liver (kidneys remove as ammonia in the urine, liver puts in blood as urea where it is then filtered by the kidneys and removed)

Question 13

Glutamate (can or cannot) enter the brain.

Answer 13

Cannot. Glutamine can.

Question 14

Glu—_____—>Gln

Answer 14

Glutamine synthase

Question 15

For each organ, name the ammonia product produced and where it goes.
Liver
Kidney
Tissues
Muscle

Answer 15

Liver–> urea, moved in blood to the kidney
Kidney–> Removes urea and remove ammonia (from Gln)
Tissues–> Gln, sent to liver, kidneys
Muscle–> Ala, sent to liver

Question 16

What tissue(s) contain glutamate dehydrogenase?

What reaction does this enzyme catalyze?

What cofactor is used?

Answer 16

Liver, peripheral tissues, Kidney, Muscle

Glu + H20—> NH4+ and alpha-ketoglutarate

NADP+—->NADPH

Question 17

What is the regulation of glutamate dehydrogenase?

Answer 17

• ATP, GTP
  + ADP, GDP

iii) The directionality of oxidative deamination by Glu dehydrogenase depends on the relative concentrations of Glu,α-ketogluterate,NH3.
iv) ATP & GTP are allosteric inhibitors of Glu dehydrogenase, while ADP & GDP are activators.

Question 18

What are the three “branched chain” amino acids?

Answer 18

Isoleucine
Leucine
Valine

Question 19

Deficiency in this enzyme creates Maple Syrup Urine Disease.

Answer 19

Branched Chain α-Keto Acid Dehydrogenase (BCKDH)

Question 20

Infant jaundice is due to a temporary lack of _____ (enzyme).

Answer 20

Bilirubin glucuronyl-transferase is low in infants (especially premature). Fluorescent light converts bilirubin to more polar products, allowing removal similar to conjugated bilirubin.

Question 21

Which two AA contain sulfur? Which can cross-link?

Answer 21

Methionine

Cysteine (can cross link)

Question 22

Break down of methionine occurs by which enzyme to create which product(s)?

Answer 22

Methionine—–>S-adenosylmethionine (SAM)

Enzyme is SAM synthase.

Question 23

In a dramatic oversimplification, we can say that ___+___ = cysteine

Answer 23

Methionine + Serine = cysteine

Met–>SAM—>SAH(S-adenosylhomocysteine) –>Homocysteine–>Cystathionine–>Cysteine

Question 24

Methionine can be recreated from homocysteine by ____ requires ____ as a cofactor.

Answer 24

Methionine synthase

B12

Question 25

Why is glutathione so important?

Answer 25

i) Thiol keeps things reduced
ii) Cofactor for several enzymes (i.e. Glutathione transferase, GST).
iii) protection against free radicals
iv) GSH keeps heme reduced in hemoglobin (fe2+) so it can bind O2 (Fe3+ is methemoglobin)

Question 26

From Trp we get (3 molecules)

Answer 26

i) Serotonin (neurotransmitter)
ii) Melatonin (hormone)
iii) Niacin (vit B3, energy, NAD)

Question 27

Name the 8 essential amino acids

Answer 27

Leucine, Isoleucine, Valine, Lysine, phenylalanine, tryptophan, methionine, threonine

Question 28

Melanin precursor AA?

Answer 28

Tyrosine

Question 29

Symptoms of homocystenuria? Defect in which enzyme?

Answer 29

Defect in CBS leading to Marfanoid-like phenotype. (ectopia lentis, kyphosis, osteoporosis)

KEY differences: Mental retardation and THROMBOSIS