Clinical Mitsouras

Question 1

How does glycerol enter gluconeogenic pathway?

Answer 1

Gylcerol —> G-3P
Enzyme: Glycerol kinase
G-3P —> DHAP
Enzyme: Glcyerol phosphate DH

Question 2

How do AAs enter gluconeogenic pathway?

Answer 2

Converted to TCA cycle intermediates and then to oxaloacetate via TCA
Alanine directly converted to pyruvate through Alanine Amino Transferase (ALT)

Question 3

How does lactate enter gluconeogenic pathway?

Answer 3

Directly converted to pyruvate through lactate DH (LDH)

Question 4

Gluconeogenesis Bypass 1

Answer 4

Phosphoenolpyruvate —> Pyruvate

Enzyme: Pyruvate kinase

Question 5

Gluconeogenesis Bypass 2

Answer 5

Fructose-6P —> Fructose-1,6BP

Enzyme: PFK-1

Question 6

Gluconeogenesis Bypass 3

Answer 6

Glucose —> Glucose-6P

Enzyme: Glucokinase

Question 7

Type I (Von Gierke’s)

Answer 7

Glucose-6P

Question 8

Type II (Pompe’s)

Answer 8

a-1,4-glucosidase

Question 9

Type III (Cori/Forbes)

Answer 9

Debranching enzyme

Question 10

Type IV (Andersen’s)

Answer 10

Branching enzyme

Question 11

Type VII (Tarui’s)

Answer 11

Phosphofructosekinase

Question 12

Type VIII

Answer 12

Phosphorylase kinase

Question 13

Type VI (Her’s)

Answer 13

Glycogen phosphorylase

Question 14

Type V (McArdle’s)

Answer 14

Glycogen phosphorylase

Question 15

Classical PKU

Answer 15

Phenylalanine catabolism/tyrosine synthesis defect

Treatment: restrict Phe in diet

Question 16

Hyperphenylalanemia (aka Type 2 PKU)

Answer 16

Phenylalanine catabolism/tyrosine synthesis defect

Treatment: Replacement therapy w/BH4 or L-Dopa or 5-HO-Trp

Question 17

PFK-1

Answer 17

Glycolysis activated

Question 18

F-1,6-BP

Answer 18

Gluconeogenesis inhibited

Question 19

Low Energy Charge

Answer 19

Gluconeogenesis OFF

Glycolysis ON

Question 20

High Energy Charge

Answer 20

Gluconeogenesis ON

Glycolysis OFF

Question 21

PEPCK

Answer 21

Stimulates gluconeogenesis

Question 22

Disease associated w/mutations in ETC components

Answer 22

LHON
MELAS
MERRF
Leigh Syndrome

Question 23

Citrate Synthase

Answer 23

Inhibited by citrate and ATP

Question 24

Isocitrate DH

Answer 24

Inhibited by NADH

Stimulated by ADP and NAD

Question 25

a-ketoglutarate DH

Answer 25

Inhibited by succinyl-CoA, NADH and ATP

Question 26

Burning Foot Syndrome

Answer 26

Pantothenic acid deficiency

Question 27

Wernicke-Korsakoff Syndrome

Answer 27

Thiamine deficiency

Question 28

Beriberi Syndrome

Answer 28

Thiamine deficiency

Question 29

PDH Deficiency

Answer 29

X-linked Leads to lactic acidosis and neurological issues Treatment: ketogenic diet, thiamine administration, muscle relaxant and anti-convulsants

Question 30

Ariboflavinosis

Answer 30

Riboflavin deficiency

Question 31

Pellagra

Answer 31

Niacin (aka Vitamin B3) deficiency

Question 32

Intermediate Metabolizers

Answer 32

Reduced activity and slower than normal metabolism | Pro & Non Pro Drugs: may experience some or a lesser degree of consequences of poor metabolizers

Question 33

Extensive Metabolizers

Answer 33

Normal enzyme activity and metabolism | Pro & Non Pro Drugs: expected response at standard dose

Question 34

Ultrarapid Metabolizers

Answer 34

Higher than normal activity & faster than normal metabolism Pro Drugs: - Too high drug levels at standard dose - High risk for ADRs and side effects Non Pro Drugs: - No response at standard dose (aka poor responder)

Question 35

Poor Metabolizers

Answer 35

``` No activity & almost no metabolism Pro Drugs: - No response at standard dose (aka poor responder) Non Pro Drugs: - Too high drug levels at standard dose - High risk for ADRs and side effects ```