metabolism

Question 1

glycogen phosphorylase control

Answer 1

covalent: PKA-> cAMP-> converts ‘b’ to ‘a’

allosteric:
in MUSCLE:
activator=5’AMP
inhibitor=ATP

Question 2

hexokinase

Answer 2

• present in muscle

- inhibited by G6P

Question 3

PFK-1

Answer 3

IN MUSCLE: 
-allosteric inhibitor= ATP and citrate
-allosteric activator= AMP
IN LIVER: 
-allosteric activator = F-2,6-Bp (fructose-2,6-bisphosphate) is a potent activator!!!

Question 4

Pyruvate kinase

Answer 4

-converts PEP to pyruvate (in the direction of glycolysis and opposite direction of gluconeogenesis)

• stimulated by= F-1,6-Bp (like feed-forward)
• inhibited by= ATP

in liver (in addition to the above…) it’s also:
stimulated by PEP
inhibited by alanine (so that biosynthesis can take place instead of glycolysis when energy profile is high!)

Question 5

glucokinase

Answer 5

• in liver and beta cells of pancreas

- glucose sensor for beta cells

Question 6

glycogen phosphorylase reaction

Answer 6

• in glycogenolysis

- Glucose to G1P

Question 7

phosphoglucomutase

Answer 7

• in glycogenolysis: G1P to G6P

- in glycogen synthesis: G6P to G1P

Question 8

Glucose-6-phosphatase

Answer 8

• converts G6P to glucose
• present in liver and kidney only, as, release of glucose in blood during starvation is needed which is provided by glycogenolysis (liver) and gluconeogenesis (liver and kidney)

Question 9

Glucose-1-P-uridyltransferase

Answer 9

• In glycogen synthesis

- Glucose-1-Phosphate +UTP—->UDP-Glucose + PPi

Question 10

Glycogen synthase

Answer 10

UDP-glucose + (glucose)n —–> UDP + (glucose)n+1

Question 11

protein phosphatase

Answer 11

• glycogen phosphorylase ‘a’ to ‘b’

- inhibited via cAMP pathway

Question 12

phosphorylase kinase

Answer 12

-glycogen phosphorylase ‘b’ to ‘a’
-activated via cAMP pathway
[in muscle, Ca2+ activates it as well]

Question 13

pyruvate carboxylase

Answer 13

• pyruvate to oxaloacetate
• uses ATP and biotin (as CO2 carrier)
• generates oxaloacetate for 2 pathways– gluconeogenesis and TCA cycle (‘anaplerosis’)

Question 14

the only enzyme of gluconeogenesis that’s present in mitochondrial matrix

Answer 14

pyruvate carboxylase

Question 15

control of pyruvate carboxylase

Answer 15

Allosteric control:

-simulated by–> Acetyl-CoA

Question 16

PEPCK (PEP carboxykinase)

Answer 16

• converts oxaloacetate to PEP
• uses GTP
• negatively regulated by insulin

Question 17

hormonal control on the balance between glycolysis and gluconeogenesis in the liver

Answer 17

• control is by regulating the amount of FBP (fructose-1,6-bisphosphate)
• this is done by regulating the phosphorylation of a bifunctional enzyme PFK-2/F-2,6-Bpase
• when glucagon–> PKA active-> phosphorylation of the bifunctional enzyme-> PFK-2 activity decreased and F-2,6-Bpase activity increased-> F-2,6-Bp drops!!–> glycolysis decreases and gluconeogenesis increases

Question 18

PDH

Answer 18

• multienzyme complex (3 enzymes)
• lipoamide arm
• converts pyruvate to Acetyl CoA

Question 19

what is the point of no return for glucose-derived carbon?why?

which enzyme controls this point?

Answer 19

Acetyl CoA
as, once the glucose is broken down to acetyl CoA it cannot be converted back to glucose (as acetyl CoA can’t be used for gluconeogenesis)

PDH controls this point

Question 20

control of PDH activity

Answer 20

(allosteric and covalent modification of PDH; and even allosteric regulation of the covalent modifiers!!!)

allosteric on PDH–> NADH/NAD+ and Acetyl CoA/CoA ratios

PDH kinase phosphorylates and inactivates PDH
PDH phosphatase dephosphorylates and activates PDH

allosteric control on modifiers:
PDH kinase–> inhibited by substrates of PDH (pyruvate); activated by products of PDH (acetyl CoA, etc.)

PDH phosphatase–> activated by Ca (in muscles) and Insulin (in adipocytes)

Question 21

citrate synthase

Answer 21

-inhibited by ATP

-

Question 22

What point in TCA cycle is particularly important for regulation during starvation?

Answer 22

• Citrate synthase inhibition by ATP
• because, during starvation the oxaloacetate should be used for gluconeogenesis; ATP is high in liver as its using other fuels and this inhibits the usage of oxaloacetate in TCA cycle in the liver!!

Question 23

isocitrate dehydrogenase

Answer 23

• inhibited by ‘fed state status’– i.e., when NADH/NAD+ ratio and ATP is high
• stimulated by ADP

Question 24

alpha-ketoglutarate dehydrogenase

Answer 24

• inhibited by its products (NADH and succinyl CoA)

- stimulated by Ca2+