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Biochem 33: Synthesis of FAs, TAGs, and Major Membrane Lipids
What might some findings be for an infant w/ respiratory distress syndrome?
a. Premature, high respirations, intercostals m. retractions (trying to help w/
respiration), cyanosis, low pO2, elevated pCO2, acidosis,granularity of lung tissue
How can serum cholesterol and triacylglyceride levels be determined?
a. Via enzyme-coupled reactions
i. Cholesterol is freed via cholesterol esterase, then oxidized in a rxn that
reduces O2 to H2O2; horseradish peroxidase is converted by H2O2
producing a color change, the intensity of which= cholesterol levels
ii. TAG is cleaved by bacterial lipase yielded glycerol that is converted to
G3P and oxidized to generated dihydroxyacetone phosphate and H2O2;
H2O2 used as reducing agent in color change rxn as before (need to run
blank b/c always have some glycerol in blood)
What is source of carbon for fatty acid synthesis? Where does synthesis primarily occur?
a. Dietary carbohydrates (excess); liver
How is cytosolic acetyl CoA produced? Why is this process circular required?
a. Glycolisis of glucose yields pyruvate that goes into mitochondria where it is
converted to Acetyl CoA by pyruvate dehydrogenase (when Acetyl CoA levels
are low) and oxaloacetate(OA) by pyruvate carboxylase (when Acetyl CoA high)
b. Oxaloacetate and Acetyl CoA join to form citrate that crosses mitochondrial
membrane and is lysed by citrate lyase to free acetyl CoA for FA synthesis
c. Required because pyruvate dehydrogenase is only found in mitochondria and
Acetyl CoA cannot cross mitochondrial membrane
How is the NADPH needed for FA synthesis produced form OA?
a. OA from citrate lyase is converted back into pyruvate by 2 steps:
i. reduced to malate by NAD+-dependent malate dehydrogenase
ii. oxidative decarboxylation of malate by NADP+-dependent malate
dehydrogenase (malic enzyme) produes NADPH!
b. Some NADPH also from glucose-6-phosphate and gluconate 6-phosphate
dehydrogenase in pentose phosphate pathway too
What leads to generation of cytosolic acetyl CoA form pyruvate? (regulator)
a. Elevated insulin/glucagon ratio
What is the rate limiting step of fatty acid synthesis? How is it regulated? What is
required by enzyme for reaction?
a. Conversion of Acetyl CoA to malonyl CoA by Acetyl CoA carboxylase
b. Enzyme activated by: citrate (allosteric), high insulin/glucagon ratio, smaller
AMP/ATP ratio
c. Enzyme inhibited by: palmityl CoA (end product; neg. feedback) and
phosphorylation by AMP dependent kinase when AMP/ATP is high (fasting)
d. Enzyme needs biotin (B7) and ATP
8. What is the ACP of Fatty Acid Synthase? How is palmitate produced? How are futile
cycles prevented?
a. Acyl carrier protein (has a phosphopantetheinyl residue
b. An acetyl CoA is attached to cysteine residue of FAS and malonate attaches to
ACP; the two condense producing a CO2 and the compound is on APC. 3
reactions lead to reduction via NADPH; shifted to cysteine so new malonate can
be added until chain reaches 16 (palmitate) and is released
c. Malonyl CoA inhibits carnitine/palmitoyltransferase I, so no entry of long chain
FAs into liver mitochondria for metabolism preventing futile cycles
9. What is major elongation of palmityl CoA in body?
a. Palmitoyl coA (C16) to stearyl CoA(C18)
10. How are double bonds (desaturation) produced in FAs? What are 2 most common
conversions in body? Why are linoleic and linolenic acid essential?
a. Via use of molecular O2, NADH, and cytochrome b5
b. Palmiitic acid to palmitoleic acid and stearic acid to oleic acid (both with double
bond b/t carbons 9 and 10)
c. We cannot produce w3 and w6 in body so linoleic and linolenic acids needed b/c
have these double bonds and can be converted to other things needed
11. How do fish acquire w3 and w6? 2 reasons linoleic acid is essential? What happens in a
deficiency of it?
a. Fish get them from eating phytoplankton; we get them from fish and plants
b. Needed for synthesis of arachidonic acid and for production of
acylglucosylceramide that keeps our skin impermeable to H2O
c. Deficiency leads to red scaly dermatitis (prob b/c skin permeable to H2O)
12. What does albetalipoproteinemia cause an inability to do?
a. Can’t assemble chylomicrons (intestines) or VLDLs (liver)
13. Where is source of glycerol for TAG in liver vs. adipose? What is produced when 2
FACoA’s are added to G3P?
a. Liver gets glycerol from G3P phosphorylated by glycerol kinase or the reduction
of DHAP from glycolysis; fat only DHAP b/c don’t have glycerol kinase
b. Phosphatidic acid
14. When do VLDLs become mature? Are they more or less dense than chylomicrons?
a. When they receive ApoE and ApoCII; more dense
15. Why do alcoholics have elevated VLDL levels? What happens to the liver as result?
a. They have high levels of NADH from alcohol which inhibits fatty acid oxidation,
so when FAs come from adipose they are packaged into VLDLs instead of
oxidized for fuel; can cause fatty liver b/c ability to secrete TAGs reduced w/ time
16. What is a genetic explanation for familial hypercholesteremia?
a. Mutation causes increased production of ApoB100 leading to increased VLDL
packaging; depending on efficacy of LPL may have only elevated VLDL or
elevated VLDL and LDL
17. How does the source of FAs for VLDL triacylglycerols differ b/t healthy and diabetics?
a. In healthy ppl source is generally xs carbohydrates; for diabetics source is xs
TAGs mobilized form adipose (will have high serum TAGs)
18. What apoprotein activates LPL? How do the Km for muscle and fat for VLDLs differ?
What happens to VLDL after it is lysed by LPL?
a. Apo CII; Km for muscle low so can receive VLDLs even when they are at low
concentrations; fat Km is high and it receives VLDLs in fed state when high
b. VLDL becomes IDL and if more TGs removed it becomes LDL
19. Which lipoprotein will be elevated in blood if diet has excess carbohydrates? Excess fat?
a. Carbs VLDL; fat chylomicrons
20. How do fats increase uptake of TGs at meal time? Why can’t they use glycerol generated
from LPL? What lipids elevated if person is LPL defective?
a. Elevated insulin/glucagon ration increases production of LPL by adipose cells so
more VLDL/chylomicrons are broken down & TGs digested to FAs and glycerol
b. Fat doesn’t have glycerol kinase so glycerol from TGs not phosphorylated for
reuse; instead this glycerol goes back to liver and fat makes its own in glycolysis
c. LPL defect leads to elevated TGs in blood + elevated VLDL and chylomicrons
21. How are TGs freed from adipose in fasting state? How do FAs travel in the blood? What
does liver form from FAs?
a. Increased glucagon= increased cAMP which activates protein kinase A; Protein
kinase A activates hormone sensitive lipase (HSL) which cleaves FAs
b. Travel in blood on albumin; liver makes ketone bodies via beta-oxidation
22. What happens in glyceroneogenisis? What enzyme is critical for it?
a. Like gluconeogensis except occurs in fat to make new G3P so that some of the
freed FAs from HSL are resynthesized into TGs before escaping (30-40%)
b. Phosphoenolpyruvate carboxykinase (takes pyruvate into PEP)
23. Where are glycerophospholipids found in body? Sphingolipids?
a. Glycerophospholipids found in cell membranes, blood lipoproteins, lung
surfactant, and bile (plus source of arachidonic acid)
b. Sphingolipids important component of cell membrane and myelin sheath
24. How are ether glycerolipids different from glycerophospholipids? Name 2
a. Ether glycerolipids have an alkyl/alkenyl chain is joined to carbon 1 via an ether
link rather than an ester bond
b. Plasmalogens and platelet activating factor
25. What glycerophospholipids are synthesized from the first method w/ addition of CDPhead group? Which via second method of CDP-diacylglycerol + head group?
a. Phosphotidylcholine, phosphatidylethanolamine, phosphatidylserine
b. Phosphatidylinositol(can be phosphorylated to PIP2, important signaling
component), cardiolipin(inner mitochondria), phosphatidylglycerol
26. Why do patients on IVs sometimes develop fatty livers?
a. Decreased ability to sythesisize phospholipids for VLDL formation because low
levels of phosphatidylcholine (lecithin) normally in diet, but not high in IV fluids
27. Where are ethanolamine plasmogens found? Choline plasmogens? Platelet activating
factor? What does PAF cause?
a. Ethanolamine plasmogen found in myelin and choline plasmogens in heart muscle
b. PAF is released from phagocytic blood cells and causes platelet aggregation,
edema, and hypotension
28. What is Zellweger’s syndrome and which ether glycerolipid may be effected by it?
a. Ppl w/ defect in peroxisome biogenisis; plasmogen (b/c synthesized in
peroxisome); can lead to early death
29. What is the major component of lung surfactant? Why is surfactant needed?
a. Dipalmitoylphosphatidylcholine; reduces pressure needed to re-inflate alveoli
30. Which phospholipase is important to free arachidonic acid for eicosanoid synthesis?
Which responds to hormonal stimuli to hydrolyse PIP2 to DAG and IP3? Which is
important to repair free radical damage?
a. Arachidoinic acid freed by phospholipase A2;also important for free radical repair
b. Phospholipase C (cleaves b/t C3 and phosphate)
31. What 2 components originally join for the synthesis of ceramide? What 2 purposes are
sphingolipids important for?
a. Palmitoyl CoA and serine; important for intercellular communication and
antigenic determinants of ABO blood groups
32. What makes up sphingomyelin (only sphingosine based phospholipid)? Cerebrosides?
a. Ceramide and phosphatidylcholine make up sphingomyelin; cerebrosides are
composed of ceramide + UDP sugars (ie galactose, glucose)
33. What disorders result from deficiency of lysosomal enzymes?
a. Lysosomal storage diseases sphingolipidoses (can’t digest sphingolipids)
34. What does galactocerebroside react with to produce sulfolipids for the brain?
a. 3’-phosphoadenosine 5’-phosphosulfate (PAPS)
35. What is leptin? When is it released? Why may obese ppl be resistant (2)?
a. Hormone released by adipose cells as TG levels rise that binds to hypothalamus
and via JAK/STAT signal induces cessation of eating (anorexigenic)
b. Obese ppl may become resistant due to constant release of leptin that either
causes desensitization of the receptor or production of factors (SOCS) that block
STAT activation
36. What are 2 actions that occur when adiponectin binds it’s receptors? How are its levels
affected by weight? What class of drug for diabetes utilizes this pathway?
a. Activation of AMP-kinase increases uptake by muscle and FA oxidation and
activation of PPARα (peroxisome proliferator-activated receptor α) causing
increased oxidation of fat by liver and muscle
b. Less adiponectin secreted as adipocytes get bigger (obesity) may be why obesity
is linked insulin insensitivity
c. Thiazolidinedione group binds and activates PPARα= reduced circulating fat and
glucose
37. What is the most common cause of coronary artery disease in US? How does this differ
from familial hypercholesterolemia?
a. Familial compound hyperlipidemia (FCH); differs b/c FCH doesn’t have lipid
deposition in the skin or tendons (xanthomas)
38. How does niacin affect lipid levels? Mechanism of action? Side effects? How does
pravastatin lower cholesterol levels?
a. Niacin lowers serum TGs and LDLs and causes rise in HDLs
b. It enhances LPL action, inhibits lipolysis of adipose, and decreases esterification
of TGs in liver (less VLDLs being produced so lower IDL and LDL as result)
c. Niacin side effects include itching and flushing
d. Statins inhibit hydroxymethylglutaryl CoA (HMG-CoA)
39. What can be measured to help determine risk of RDS? What can be given to mother 72
hrs prior to deliver of child <33 weeks to reduce incidence/mortality of RDS?
a. Head circumference (ultrasound), fetal arterial oxygen saturation, and ration of
phosphatidylcholine to sphingomyelin in amniotic fluid
b. corticosteroids
40. What are perilipins? How are their levels affected by obesity?
a. Adipocyte phosphoproteins that bind TG droplets and regulate the accessibility of
TGs to lipases; levels decrease in obesity (so more TGs lysed and in blood)
41. Destruction of what region of hypothalamus causes obesity? Weightloss? What hormones
cause satiety signals (2)?
a. Ventromedial nucleus or paraventricular nucleus lesions cause obesity; weight
loss in lateral hypothalamus lesion
b. Leptin and glucagonlike peptide 1 (GLP-1)
42. 2 ways that nonesterified fatty acids (NEFA) can lead to insulin resistance?
a. Elevated free FA in blood used by muscle leading to buildup of Acetyl CoA in
mitochondria that is exported as citrate and inhibits PFK-1; this inhibits glucose
metab in muscle so less is taken up b/c it is not being used
b. In beta-cells of pancreas NEFA raise the acetyl CoA in mitochondria activating
pyruvate carboxylase and increasing NADPH levels which blunts the NADPH
rise that normally occurs when glucose levels rise (leading to insulin release)
43. What is required to diagnose metabolic syndrome?
a. At least 3 of the following:
i. Increased weight circumference: 40 + men, 35+ women
ii. Elevated griglycerides (> 150 mg/dL)
iii. Reduced HDL (<40 mg/dL for men, <50 mg/dL for women)
iv. Elevated blood pressure (> 130/85 mm Hg)
Elevated fasting glucose (>