Biochem

Question 1

Homocysteine can be converted into ________ or ______

Answer 1

methionine or cystathione

Question 2

homocysteine to cystathione requres ______, _____ and _____.

Answer 2

Serine, B6 (pyridoxine) and cystathionine synthase

Question 3

homocysteine to methionine requires what co-factors/enzymes?

Answer 3

homosysteine + 5 methyl THF + methylcobalumin ==> methionine + THF + B12

Enzyme = methionine synthase

Question 4

What are the most serious serious consequences of homocystinuria?

Answer 4

hypercoagulability and thromboembolic occlusion ==> premature acute coronary syndrome (e.g. 12 yr old athlete with a heart attack in increased serum methionine levels)

Question 5

What enzyme is likely eleveated in homocystinuria?

Answer 5

cystathionine synthase (B-6 cofactor; requires serine AA) catalyzeses conversion of homocysteine to cystathionine.

Question 6

homocystinuria is associated with what clinical features?

Answer 6

ectopia lentis (ocular lens displacement)
intellectual disability
thrombosis/premature acute coronary syndrome

Question 7

What amino acid is essential in pt. with homocystinuria?

Answer 7

cysteine! cannot convert homocystein to cyctathionine to cysteine

Question 8

what amino acid is essential for rapidly deviding tumor cells?

Answer 8

asparagine (asparagine synthase converts aspartate to asparagine)

• tumor cells cannot produce asparagine quickly enough
• asparaginase chemothapy drug leads to lysis of rapidly growing cells

Question 9

what enzyme is deficient in maple syrup urine disease?

Answer 9

defiiency in branched chain alpha-ketoacid dehydrogenase

-leads to buidup of

Question 10

defiiency in branched chain alpha-ketoacid dehydrogenase causes _____, which manifests due to buildup of what AAs?

Answer 10

branched gain amino acids

Leucine, isoleucine, valine

Question 11

what are the ketogenic aminio acids?

Answer 11

lysine,

Question 12

What AA is essential in PKU?

Answer 12

tyrosine

PKU = pehnylalanine hyoxylase deficiency, which converts phenalalanine to tyrosine

Question 13

what in addition to pehnylalanine hyoxylase deficiency can cause PKU?

Answer 13

deficiency in biosynthesis of tetrahydrobiopterin (BH4)

Question 14

BH4 is a co-factor for conversion of phenylalanine to tyrosine and required for monoamine biosynthesis. What is another important role for BH4 that is unrelated to these processes?

Answer 14

co-factor in nitrous oxide production

Question 15

What is the source of nitrogen for the formation of NO?

Answer 15

arginine

L -arginine + BH4 + nitrous oxide synthetase =>NO+ prod

Question 16

symptoms of hyperamonemia are caused by depletion of what TCA intermediate?

Answer 16

alpha-ketoglutarate (shuts down TCA cycle)

used by rxn in liver tht leads to alanine (NH3) + alpha-ketoglutarate => pyruvate + glutamate (NH3)

Question 17

what TCA/glycolytic rxns are most affected by thiamine deficiency?

Answer 17

pyruvate dehydrogenase (B1 cofactor)
alpha-ketoglutarate dehydrogenase (B1 co-factor)

also transketolase (PRshunt)

Question 18

what TCA/glycolytic rxns are most affected by chronic alcohol consumption?

Answer 18

pyruvate dehydrogenase (B1 cofactor)

• NAD+ is depleted by alcohol dehydrogenase and acetaldehyde dehydrogenase resulting in INCREASED NADH/NAD+ ratio
• depletion of NAD+ impairs several dehydrogenase rxns including:

pyruvate dehydrogenase (B1 cofactor)

alpha-ketoglutarate dehydrogenase (B1 co-factor)

Malate dehydrogenase

isocitrate dehydrogenase

Question 19

what enzyme converts phenylalanine to tyrasine?

Answer 19

phenylalanine hydroxylase

Question 20

what enzyme converts tyrasine to L-dopa?

Answer 20

tyrasine hydroxylase

Question 21

what enzyme is inhibited by carbadopa? what co-factor is required for this enzyme:?

Answer 21

dopamine decarboxylase (converts L-dopa to dopamine)

B6

Question 22

what is homosystinuria caused by

Answer 22

autosomal recessive mutation of cystathionine beta synthase which leads to the inability to form cysteine from homocysteine and the buildup of methionine and homocystein

MAJOR CHARACTERISTICS THAT DISTINGUISH FROM MARFANS = INTELLECTUAL DISABILITY AND HYPERCOAGULABILITY - e.g. thombosis of the superior sagital sinus

Question 23

insulin has what effect on phosphofructokinase-2 (PFK2)?

Answer 23

increases activity promoting the conversion of fructose-6-phosphate to fructose-2,6-bisphosphate

Question 24

what is the effect of fructose-2,6-bisphosphate (F2,6BP) on phosphofructokinase-1 (PFK1) vs fructose-1,6-bisphosphatase (F1,6BPase)?

Answer 24

F2,6BP is increased under the presence of insulin and increases the activity of PFK1 (promoting conversion of F6P to F1,6,BP)

F2,6BP also decreases the activity of F1,6BPase (inhibiting the gluconeogenic conversion of F1,6,BP to F6P when in the fed state)

Question 25

what is the effect of glucagon on fructose-2,6-bisphosphate? How does this lead to the formation of glucose?

Answer 25

glucagon activates fructose-2,6-bisphosphatase which converts fructose-2,6-bisphosphate (F2,6BP) to F6P

the function of this step is to eliminate the positive regulator of PFK1 (which under the influence of insulin and F2,6PB promote glycolysis) and remove the inhibition of F1,6BPase (to support gluconeogenisis)

activation of F1,6BPase promotes the conversion of F1,6BP to F6P

(allowing phosphoglucose isomerase to convert F6P into G6P and then glucose-6-phosphatase to convert G6P to glucose for gluconeogenesis)

Question 26

what are the hydrophobic amino acids?

Answer 26

TTP VIP GAL

tyrosine
triptophan
phenyalanine

valine
isoleucine
proline

Glycine
Alanine
Leucine