FA synthesis/degradation Flashcards
Major regulatory enzyme of FA synthesis
Acetyl Co Carboxylase; uses ATP and bicarbonate (carbon source), converts Acetyl CoA –> Malonyl CoA, activated by citrate and inhibited by Palmitoyl CoA
FA synthesis occurs in the ____, whereas FA degradation (beta-oxidation) occurs in the _____
FA synthesis = cytoplasm, beta-oxidation = mitochondria (makes sense because Acetyl CoA can immediately be shuttled into TCA)
Tell me about Malonyl CoA. What reaction is it the product of? Does it regulate any processes?
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)
Why is a diet high in fructose bad?
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.
Tell me about Palmitoyl CoA – how it is made and what is its fate.
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.
What are the ketone bodies?
acetoacetate, acetone, and b-hydroxybutyrate
Does the liver use ketone bodies!
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.
When ketone production exceed need, what is likely to happen?
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.
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?
HbA1C. Shows the glucose profile for ~ 3 months. Should be relatively normal if the episode is a fluke.
Give me a lil’ background on Arachidonatic Acid (AA)
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
Give me a lil’ background on Arachidonatic Acid (AA)
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
Through what receptor-mediated pathways do Prostaglandins take effect?
GPCRs!
Gα = AC and cAMP
Gq = PLC, IP3 and increase of Ca2+ = contract of smooth muscles
Through what receptor-mediated pathways do Prostaglandins take effect?
GPCRs!
Gαs = AC and cAMP
GαQ = PLC, IP3 and increase of Ca2+ = contract of smooth muscles
Lipoprotein Lipase differs from Hormone Sensitive Lipase in that it…?
Lipoprotein Lipase acts in the blood on exogenous lipid Chylomicrons and VLDL metamorphosis into LDL
FA traveling in the blood is sequestered by ____.
Serum albumin.
A consequence of dyslipidemia is excess LDL in the bloodstream, attracting the attention of which kind of cells?
Macrophage foam cells. Bad. This causes atherosclerotic heart disease and possible stroke.
Hormone Sensitive Lipase is activated by ______
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
Hormone Sensitive Lipase is activated by ______
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
Liver only enzyme involved in both Glycogenolysis and Gluconeogenesis.
Glucose-6-phosphatase.
Patient presents to the ER after exposure to Carbon Monoxide. Why is this worrisome? What is happening biochemically?
CO and CN- sequester O2 at complex 4 of ETC so there is an electron backup and no ATP production.
What is a hallmark symptom of Van Gierke’s? Result of which enzyme deficiency?
Hypoglycemia.
Glucose 6 phosphatase is deficient so glucose cannot be released from glycogen stores nor produced from scratch by way of gluconeogenesis.
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?
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.
SOS is a ____ protein that is involved in the _____ receptor pathway and is responsible for activating ______.
SOS is a GEF! Exchanges GDP for GTP in Ras G monomeric protein of MAP/ERK pathway of RTK receptor.
Which is slower: GPCR of RTK receptor-mediated pathways? Why?
RTK because mostly induces transcriptional regulation.
This toxin affects Gαs unit of GPCR causing loss of intrinsic GTPase function. What is the toxin? What is the result?
Cholera.
No GTPase, adenylyl cyclase will be forever active. expect a lot of cAMP!
______ is degraded by phosphodiesterase.
cAMP.
Mutations in this pathway lead to a great deal of cancer.
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.
This phosphorylated cytoplasmic fella leads to insertion of Glut 4 receptors and FOXO1 transcription factors.
Akt! Part of PI3K RTK pathway, largely activated by insulin.
This receptor pathway can lead to influx of cytoplasmic Ca2+ messengers
PLC
