MISC pathways 2

Question 1

Key regulated step in glycogen synthesis involves which enzyme?

Answer 1

Glycogen synthase

G1P –> UDP glucose —-> glycogen

UDP-glucose gets activated and binds to glycogenin.
UDP gets displaced and transferred to OH group at c4 terminus of glycogen.

Question 2

If branching enzyme for glycogenesis is missing, what sx can manifest?

Answer 2

slower glycogen break down (due to linear glycogen) –>

hypoglycemia during fasting or decreased exercise tolerance

Question 3

In the fed state, glycogen synthase is allosterially activated by _____

Answer 3

G-6-P (which is increased after meals)

• this occurs in both liver and skeletal muscle

Question 4

Glycogen cannot be converted to free glucose in (skeletal m/liver)?

Answer 4

skeletal

- must go thru cori cycle

Question 5

How does glycogen degredation occur in muscle contraction?

Answer 5

1. During muscle contraction, the membrane depol + promotes Ca2+ release
2. Ca2+ binds to calmodulin + activates phosphorylate kinase
3. This phosphorylates glycogen phosphorylase (active)
4. this degrades Glycogen to G1P

Question 6

Glycogen phosphorylase does what? Is it active or inactive when it is phosphorylated?

Answer 6

It breaks down glycogen –> G1P

It is active when phosphorylated

(glycogen phosphorylase kinase a phosphorylates glycogen phosphorylase, which results in the degradation of glycogen)

*note: this is the opposite from PDH complex and pyruvate kinase, and PFK-2, which are all active when De-P!

Question 7

Glucagon (liver) and epi (m and liver) inhibits glycogen synthesis how?

Answer 7

1. BInd to memb recptr
2. activates cAMP
3. activates PKA
4. Phosphorylates GLYCOGEN SYNTHASE, which makes it inactive
5. glycogen synth is inhibited

(insulin dephos glycogen synth)

Question 8

Glucose-6-phosphate dehydrogenase deficiency

Answer 8

(most common enzyme def linked to hemolytic anemia)

G6PD deficiency impairs RBC ability to form NADPH –> cant guard against ROS –>
Sulfydryl groups in Hb becomes oxidized, forming cross links and aggregating in RBCs (HEINZ BODIES) –>
Aggregates make RBC membrane rigid –>
RBC destruction

Question 9

3 conditions when ketone body formation occurs. What do they all have in common?

Answer 9

1. starvation
2. DKA
3. alcoholic ketoacidosis

All 3:

1. have very low insulin lvls
2. high CRH
3. high amt substrate (FA - fasting +DKA, ethanol)

Question 10

3 lipoprotein pathways

Answer 10

1. dietary fat pathway (chylomicron pathway)
2. VLDL pathway
3. HDL pathway

Question 11

Dietary fat pathway

Answer 11

TG rich particles deliver dietary fat to skeletal m and adipose tissue

Question 12

VLDL pathway

Answer 12

TG DERIVED from liver is delivered to skeletal m and adipose tissue

Question 13

HDL pathway

Answer 13

Resevoir and transport system for a variety of lipids (ie: cholesterol)

Imp transport of cholesterol from periphery to liver

Reverse Cholesterol transport - important against atherosclerosis

Question 14

Linoleic acid

Answer 14

precursor for aa that is the substrate for PG synthesis

Question 15

linolenic acid

Answer 15

precursor for w-3-FA that is important for growth/development

Question 16

coenzyme for acetyl coA carboxylase (converts acetyl coA to malonyl coA)

Answer 16

Biotin

Question 17

HMP is a major supplier of NADPH for _______ synthesis

Answer 17

Fatty acid

Question 18

cytosolic _____ is from the mitochondria

Answer 18

acetyl coA

Question 19

Insulin activates protein ________ which dephosphorylates ______, thus activating this enzyme

Answer 19

protein phosphatase

acetyl coa carboxylase (ACC)

Question 20

Glucagon increases intracellular cAMP, leading to activate cAMP dependent protein kinase, which phosphorylates and thus, ______ ACC

Answer 20

Inhibiting

(acetyl coA can no longer be converted to malonyl coA

Question 21

FAs produced are stored as ____

Answer 21

TAGs

major energy reserve of the body

Question 22

Glycerol phosphate is produced in the _______ and _____ and is the initial acceptor of ______ during TAG synthesis

Answer 22

Liver and adipose tissue

Fatty acetyl coAs

Question 23

Glycerol phosphate is produced from:

It can get converted to

Answer 23

Glycerol and Glyceraldehyde 3 P (indirectly)

can get converted to TAGs and Glyceraldehyde 3 P

Question 24

Chroinic alcoholism causes hyperlipidemia in both ___ and ____. why? (4)

Answer 24

liver, serum

1. ethanol oxidized to acetyl coA –> FA in liver
2. High NADH/NAD+ slows TCA cycle and FA oxidation
3. Glycerol 3-P + FA –> TAGs
4. Liver unable to prod/sec. VLDL –> hepatic fat build up.

Question 25

Fatty acids are more (reduced/oxidized) than proteins and carbs. So more E can be extracted when they are (reduced/oxidized)

Answer 25

reduced, oxidized

Question 26

Hormone sensitive lipase has what action on fatty acid oxidation?

Answer 26

It is a major pathway for regulating it.

It removes FA from C1 or C3 of TAG. HSL is active when it is PHOSPHORYLATED by protein kinase.
(ie: when epi is present)

Question 27

Insulin (activates/deactivates) HSL?

Answer 27

Inactivates:

prevents HSL from removing FA form TAG and providing substrate to make glucose.

Question 28

Why doesnt palmitate get degraded when FA synth is occuring in the cytosol?

Answer 28

Newly made palmitate cannot be transferred into the MITO for degradation bc malonyl coA inhibits CPT1 on outer mito membrane

*note malonyl coA is high [ ] during FA synth

Question 29

3 examples of ketone bodies

- who uses them, and who doesnt

Answer 29

1. acetoacetate
2. 3-hydroxybutyrate
3. acetone

• first fuel choice for cardiac and renal cortex
• not used by liver

Question 30

During times of starvation, lvls of ketone bodies ____.

Answer 30

increase

Question 31

How does ketoacidosis result from Type I diabetes?

Answer 31

1. insulin resistant
2. HSL highly active –> release lg quantities of FA from adipose
3. FA oxidation

--> produce excess acetyl coA --> 
ketone body pathway -->
2 strong acids (ketones) -->
lower blood pH 
(metabolic ketoacidosis)