FA synthesis/degradation

Question 1

Major regulatory enzyme of FA synthesis

Answer 1

Acetyl Co Carboxylase; uses ATP and bicarbonate (carbon source), converts Acetyl CoA –> Malonyl CoA, activated by citrate and inhibited by Palmitoyl CoA

Question 2

FA synthesis occurs in the ____, whereas FA degradation (beta-oxidation) occurs in the _____

Answer 2

FA synthesis = cytoplasm, beta-oxidation = mitochondria (makes sense because Acetyl CoA can immediately be shuttled into TCA)

Question 3

Tell me about Malonyl CoA. What reaction is it the product of? Does it regulate any processes?

Answer 3

Product of Acetyl CoA Carboxylase reaction in FA synthesis in cytoplasm.

Inhibits FA transport into mitochondria by CPTI (you don’t want FA synthesis and degradation happening at the same time; malonyl CoA increase indicates a lot of synthesis which is going to inhibit shuttling of FA into mitochondria for breakdown)

Question 4

Why is a diet high in fructose bad?

Answer 4

Fructokinase is not regulated– increase in citrate and FA synthesis.

In the liver, Glucokinase is tightly regulated and doesn’t phosphorylate Glucose unless there is a crap ton. (That’s good because it keeps Glucose as Glucose to be transported to peripheral tissues and it prevents production of FA synthesis reactants.

Fructokinase on the other hand is not regulated and so with a rush of Fructose, you get a rush of Glycolysis and TCA. Result is increase in Citrate levels which exit the cell to be made into fat.

Question 5

Tell me about Palmitoyl CoA – how it is made and what is its fate.

Answer 5

Made in the cytoplasm as product of FA Synthesis. 20 C. Further modifications occur at the SER. Negatively regulates beta-oxidation of FA by inhibiting FA transport into mitochondria by CPT 1.

3 FA with gylcerol (formed in glycolytic pathway) together make TAGs. Exit hepatic cells as VLDL. In blood, can be acted upon by lipoprotein lipases to free FA (sequestered by serum albumin and taken up by adipocytes and muscle). VLDL becomes LDL in the blood and taken up by LDL receptor laden peripheral cells.

Question 6

What are the ketone bodies?

Answer 6

acetoacetate, acetone, and b-hydroxybutyrate

Question 7

Does the liver use ketone bodies!

Answer 7

No, silly! The liver is wildly selfless. It makes ketone bodies for the rest of the body.

b-hydroxybutrate is made energetically useful by the acyl transferase enzyme, which is NOT available in liver. Ensures that acetoacetate and its acetone and b-hydroxybutryate derivates are used only for export to peripheral tissues.

Question 8

When ketone production exceed need, what is likely to happen?

Answer 8

Ketoacidosis. pH of blood will drop due to acidic qualities of ketones.

Common in Type 1 Diabetes (insulin dependent). If a T1 patient stops taking insulin, no glucose is being taken up into cells and the body freaks out and asks for energy in some other format – ketone production results.

Question 9

A patient presents with a DKA episode. How might you determine if the patient’s episode is a fluke or the result of poorly controlled diabetes?

Answer 9

HbA1C. Shows the glucose profile for ~ 3 months. Should be relatively normal if the episode is a fluke.

Question 10

Give me a lil’ background on Arachidonatic Acid (AA)

Answer 10

20 C FA
From diet and Linoleic essential FA conversions
Exists mostly at glycerophospholipis in membrane
Released by Phospholipase A 2
Precurosor of Eicosanoids: Prostaglandins, Lipoxins, Leukotrienes

Question 11

Give me a lil’ background on Arachidonatic Acid (AA)

Answer 11

20 C FA
From diet and Linoleic or linolenic essential FA conversions
Exists mostly at glycerophospholipis in membrane (released by phospholipase A2C - PLC), but also in adipocytes (released by hormone sensitive lipase)
Precurosor of Eicosanoids: Prostaglandins, Lipoxins, Leukotrienes

Question 12

Through what receptor-mediated pathways do Prostaglandins take effect?

Answer 12

GPCRs!
Gα = AC and cAMP
Gq = PLC, IP3 and increase of Ca2+ = contract of smooth muscles

Question 13

Through what receptor-mediated pathways do Prostaglandins take effect?

Answer 13

GPCRs!
Gαs = AC and cAMP
GαQ = PLC, IP3 and increase of Ca2+ = contract of smooth muscles

Question 14

Lipoprotein Lipase differs from Hormone Sensitive Lipase in that it…?

Answer 14

Lipoprotein Lipase acts in the blood on exogenous lipid Chylomicrons and VLDL metamorphosis into LDL

Question 15

FA traveling in the blood is sequestered by ____.

Answer 15

Serum albumin.

Question 16

A consequence of dyslipidemia is excess LDL in the bloodstream, attracting the attention of which kind of cells?

Answer 16

Macrophage foam cells. Bad. This causes atherosclerotic heart disease and possible stroke.

Question 17

Hormone Sensitive Lipase is activated by ______

Answer 17

Glucagon! Triggering Gα of GPCR for AC and cAMP!!
Mobilizes triacylglycerol stores of adipocytes
FA go to liver (by way of serum albumin of course) for ketone production

Question 18

Hormone Sensitive Lipase is activated by ______

Answer 18

Glucagon! Triggering Gαs of GPCR for AC and cAMP!!
Mobilizes triacylglycerol stores of adipocytes
FA go to liver (by way of serum albumin of course) for ketone production

Question 19

Liver only enzyme involved in both Glycogenolysis and Gluconeogenesis.

Answer 19

Glucose-6-phosphatase.

Question 20

Patient presents to the ER after exposure to Carbon Monoxide. Why is this worrisome? What is happening biochemically?

Answer 20

CO and CN- sequester O2 at complex 4 of ETC so there is an electron backup and no ATP production.

Question 21

What is a hallmark symptom of Van Gierke’s? Result of which enzyme deficiency?

Answer 21

Hypoglycemia.

Glucose 6 phosphatase is deficient so glucose cannot be released from glycogen stores nor produced from scratch by way of gluconeogenesis.

Question 22

Patient recently completed anti-malaria drug therapy but had an adverse reaction. Patient is extremely pale, reports black urine. Lab results indicate hemolytic anemia. What is going on with this poor soul?

Answer 22

Glucose-6-phosphate dehydrogenase deficiency.

GCPDH produces NADPH to keep glutathione ready to do its reducing job and fight off ROS. When deficient, ROS build up and erythrocytes lyse.

Sex-linked recessive disorder. Presents largely in males b/c of hemizygous inheritance.

Question 23

SOS is a ____ protein that is involved in the _____ receptor pathway and is responsible for activating ______.

Answer 23

SOS is a GEF! Exchanges GDP for GTP in Ras G monomeric protein of MAP/ERK pathway of RTK receptor.

Question 24

Which is slower: GPCR of RTK receptor-mediated pathways? Why?

Answer 24

RTK because mostly induces transcriptional regulation.

Question 25

This toxin affects Gαs unit of GPCR causing loss of intrinsic GTPase function. What is the toxin? What is the result?

Answer 25

Cholera.

No GTPase, adenylyl cyclase will be forever active. expect a lot of cAMP!

Question 26

______ is degraded by phosphodiesterase.

Answer 26

cAMP.

Question 27

Mutations in this pathway lead to a great deal of cancer.

Answer 27

Ras/ERK RTK pathway.
variety of Ras mutations drives 1/3 human cancers.
consituitve actiation of ERK is primary driver of cell proliferation in most cancers.

Question 28

This phosphorylated cytoplasmic fella leads to insertion of Glut 4 receptors and FOXO1 transcription factors.

Answer 28

Akt! Part of PI3K RTK pathway, largely activated by insulin.

Question 29

This receptor pathway can lead to influx of cytoplasmic Ca2+ messengers

Answer 29

PLC