Feb6 M3-Normal and Abnormal Carbohydrate Metabolism - 2

Question 1

what happens to pyruvate before enters the TCA cycle

Answer 1

converted to acetyl-CoA by pyruvate dehydrogenase (PDH)

Question 2

input and output of pyruvate to acetyl CoA

Answer 2

input: CoA and NAD
output: NADH and CO2

Question 3

3 ways conversion of pyruvate to acetyl CoA is regulated

Answer 3

1. phosphorylation
2. end product inhibition (NADH and acetyl CoA)
3. need cofactors (thiamine and lipoic acid)

Question 4

PDH abnormalities common where

Answer 4

in cancer. because of Warburg effect (PDH activity is suppressed)

Question 5

genetic PDH deficiency: name of disease

Answer 5

Leigh’s syndrome

Question 6

(in PDH deficiencies) Leigh’s syndrome what population + blood test + symptoms

Answer 6

in children. high lactate and pyruvate (chronic lactic acidosis). severe neuro defects. lethal.

Question 7

(in PDH deficiencies): thamine deficiency: name of disease

Answer 7

Wernicke-Korsokoff syndrome

Question 8

Wernicke-Korsokoff syndrome symptoms + one possible cause

Answer 8

encephalopathy and psychosis

possible cause: alcoholic (low thiamine uptake + poor thiamine processing bc of lactic acidosis)

Question 9

toxic PDH deficiency and pathophgy (+main prob is where)

Answer 9

arsenic toxicity. binds lipoic acid, blocking this cofactor. main prob in CNS bc need glucose

Question 10

useful products generated in Kreb’s cycle

Answer 10

NADH, FADH2, GTP

Question 11

how TCA cycle starts and why CO2 made

Answer 11

start with 2C acetyl-CoA. combines with oxaloacetate (4C) to make citrate (6C). 2C losts on the way in 2 CO2

Question 12

most common TCA deficiency

Answer 12

don’t exist. incompatible with life

Question 13

energy released produced in whole ETC and how much serves to make ATP

Answer 13

-53 Kcal per mol
+22 kcal per mol of ATP made (3 mol ATP bc each is -7.3 kcal per mol)
31 kcal to waste (inefficient system)

Question 14

protein using H+ gradient IMM to matrix to make ATP

Answer 14

ATP synthase

Question 15

UCP function

Answer 15

let H+ leak to matrix and energy of the gradient lost to heat

Question 16

3 ways ETC may stop working

Answer 16

cyanide poisoning (CN)
CO poisoning
Leigh’s syndrome

Question 17

CN poisoning pathophgy

Answer 17

blocks Fe3+ in complex IV (CNs damage)

Question 18

treatment of CN poisoning

Answer 18

vitamin B12

Question 19

CO poisoning pathophgy

Answer 19

binds Fe2+ in complex IV and stops it

Question 20

Leigh’s syndrome pathophgy

Answer 20

genetic mutation in complex IV (misfolds)

Question 21

how obtain glucose when fasting

Answer 21

liver supplies it from its glycogen stores

Question 22

how glucose transferred to glycogen production

Answer 22

glucose 6 P from 1st step glycolysis (GK liver HK muscle) becomes glucose 1P (done by other enzyme)

Question 23

how glucose 1P becomes glycogen

Answer 23

glucose 1P couples to UTP (enzymatic) to make UDP-glucose.

Question 24

how UDP glucose makes glycogen

Answer 24

UDP-glucose binds to glucose via glycogen synthase and more UDP-glucose will be able to do that. UDP released

Question 25

step controlled in glycogen synthesis and how

Answer 25

glycogen synthase
insulin upregulates it
glucagon downregulates it

Question 26

muscle and liver % weight in glycogen and which has more glycogen

Answer 26

liver 10% glycogen
muscle 1-2% glycogen
muscle has more bc we have more muscle

Question 27

what breaks down glycogen (EXAM) and how is it regulated

Answer 27

glycogen phosphorylases. makes glucose 1P from glycogen
insulin downregulates it
glucagon upregulates it

Question 28

other name for gluconeogenesis

Answer 28

Cori cycle

Question 29

which organs do Cori cycle

Answer 29

initially liver, after couple hours, liver and kidneys (kidneys do 40%)

Question 30

challenge of gluconeogenesis and how to overcome it

Answer 30

3 irreversible steps of glycolysis have to be reversed

4 reactions are needed to do that

Question 31

why need gluconeogenesis

Answer 31

after 12 hours of fasting, liver glycogen is gone

Question 32

1 step of 4 in Cori cycle to get around irreversible rxs

Answer 32

pyruvate (may come from lactate) becomes oxaloacetate (pyruvate carboxylase)

Question 33

2nd step of 4 in Cori cycle to get around irreversible rxs

Answer 33

OAA makes phosphoenoylpyruvate (enzyme PEPCK)

Question 34

3rd step of 4 in Cori cycle to get around irreversible rxs

Answer 34

fructose 1,6 biphosphate makes fructose 6P (fructose 1,6 biphosphatase)

Question 35

4th step of 4 in Cori cycle to get around irreversible rxs

Answer 35

glucose 6P to glucose (glucose 6 phosphatase)

Question 36

most regulated step of Cori cycle and how

Answer 36

fructose 1,6 biP to fructose 6P. glucagon upregulates it

insulin downregulates it

Question 37

other regulated step in Cori cycle

Answer 37

acetyl-CoA upregulates pyruvate carboxylase (pyruvate to OAA)

Question 38

how Cori cycle makes glucose (how amino acids used to make glucose)

Answer 38

amino acids go in TCA cycle, form TCA cycle intermediates. one is OAA (in step 2 of Cori cycle)

Question 39

TF PFK also regulated by glucagon and insulin (fructose 6 to fructose 1,6 biP)

Answer 39

true. insulin upregulates it.

glucagon downregulates it

Question 40

glucose to lactate and lactate to glucose happen where

Answer 40

glucose to lactate in muscle

lactate to glucose in liver

Question 41

McArdle disease pathophgy and consequence

Answer 41

no glycogen phosphorylase in muscle. can’t do strenuous exercise. damaged (lack E + glycogen accumulates)

Question 42

Von Gierke disease pathophgy and consequence

Answer 42

no glucose-6-phosphatase in the liver (last step of Cori cycle). hypoglycemia when fasting

Question 43

why alcoholism can cause hypoglycemia

Answer 43

• alcohol oxidation (made into acetaldehyde and then acetate) makes a lot of NADH.
• high NADH enviroment = pyruvate becomes lactate and OAA becomes malate (so pyruvate and OAA not use for Cori cycle anymore)