Lipid Lecture Flashcards
Where does synthesis of fatty acids occur?
Liver
Where and how are fatty acids stored (summary)?
as triglycerides in adipose tissue
What enzyme is integral to the first stage of fatty acid synthesis?
acetyl CoA carboxylase
What enzyme is integral to the second stage of fatty acid synthesis?
fatty acid synthase
What is required for fatty acid synthesis?
Cytosolic acetyl CoA (exported from mitochondria as citrate) and NADPH (pentose PP and malate to pyruvate reaction)
A high insulin/glucagon ratio induces synthesis of:
Pyruvate dehydrogenase,
Malic enzyme,
and citrate lyase
The pentose phosphate pathway starts with ____ and creates ____, which is necessary for lipid synthesis.
Glucose-6-phosphate,
NADPH
Malic enzyme converts ___ to ___.
Malate to pyruvate
Acetyl CoA carboxylase requires ____, which is a B vitamin.
Biotin
Acetyl CoA converts ___ to ____.
Acetyl CoA to Malonyl CoA
What regulates acetyl CoA carboxylase?
Palmitoyl CoA inhibits, and citrate activates, phosphorylation inactivates
insulin indirectly activates by activating phosphatase
Phosphatase is regulated by ___.
insulin activates it
The fatty acid synthase complex ___(action)___. It is __#___ protein(s) with # different enzymatic activities and an ______. It is a ____ of identical polypeptides arranged head to tail.
sequentially adds 2 carbon units from malonyl CoA to the growing fatty acid chain.
It is one protein with 7 different enzymatic activities and an acyl-carrier protein
It is a dimer of identical polypeptides arranged from head to tail.
After __#__ cycles of synthase activity, a final ________ occurs.
6 cycles of synthase activity precede a final thioesterification to palmitate
Components of each cycle of the fatty acid synthase complex
(There is one for the steps and one for the enzymes)
(One of the steps in the cycle is the last in one and first in the other)
- Condensation
- Reduction
- Dehydration
- Reduction
- “Scoot over” (Transacetylation)
- Malonyl Transacylase
- beta ketoacyl synthase
- Ketoacyl reductase
- dehydratase
- enoyl reductase
Acyl groups of FA synthase are transferred as ____ on the ______ residue of _____ or the ___ of a ___ residue.
thioesters, phosphopantetheinyl, acyl carrier protein, -SH, Cys
What is the balanced equation of fatty acid synthesis?
8 acetyl CoA + 7 ATP + 14 NADPH + 14 H+ —> Palmitate + 8 CoASH + 7 ADP + 7 Pi + 14 NADP+
What is the difference between fatty acid synthesis and fatty acid oxidation?
Fatty acid synthesis requires ACP as acyl group carrier, NADPH as an electron donor and malonyl-CoA as a 2 carbon donor.
Fatty acid oxidation uses CoA as acyl carrier, FAD and NAD+ as electron acceptors, acetyl-CoA as 2 carbon product
What regulated fatty acid synthesis?
Acetyl-CoA carboxylase is activated by citrate and insulin/phosphatase and deactivated through phosphorylation and inhibited by palmitoyl CoA
Fatty acid synthesis is activated by a high insulin/glucagon ratio and transcription factos (USF’s or upstream regulatory factors, SREBPs or sterol response element binding protein, and ChREBP or carbohydrate responsive element binding protein)
Inhibition of carnitine palmitoyltransferase or CPTI by malonyl CoA (prevents simultaneous oxidation and synthesis of fatty acids)
Palmitate can be modified to form other FAs through ____.
Elongation, desaturation, formation of triacylglycerol, formation of phospholipids and sphingolipids, and formation of prostaglandins from linoleic acid
Where does elongation of fatty acids occur?
In the endoplasmic reticulum (by fatty acid elongase)
What is a common product of fatty acid elongation?
Stearic acid
What is the difference between the mechanism of elongation and fatty acid synthesis?
The fatty acyl chain is attached to coenzyme A instead of ACP
Where does the desaturation of fatty acids occur?
In the endoplasmic reticulum
What are the steps of desaturation of fatty acids (by enzyme required)?
- NADH-cyt b5 Reductase
- Cytochrome b5
- Desaturase
What is required for the desaturation of fatty acids?
Molecular oxygen, flavoprotein with FAD as a prosthetic group (NADH-cyt b5 reductase), Iron (cytochrome b5, desaturase because active site has iron atoms coordinated to histidine)
What are the steps of the synthesis of triacylglycerols?
- Glycerol from the liver using glycerol kinase and ATP, or glucose to DHAP using NADH
- Glycerol-3-P
- Phosphatidate
- Diacylglycerol
- Triacylglycerol
- Blood VLDL in the liver or to adipose stores
What are the fates of triacylglycerols?
Adipose stores or blood VLDL if it goes to the liver (using ApoB-100)
Insulin stimulates _______ of triglycerides
adipose storage
Adipose tissue lacks ____.
glycerol kinase
What causes the release of fatty acids from adipose triglycerides?
Phosphorylated hormone sensitive lipase is active and breaks down triacylglycerols in adipose tissue
Phospholipid synthesis requires ____ or vitamin __.
Inositol
B8
Respiratory distress syndrome occurs when there is failure to __________ in lung surfactant.
to produce enough phosphotidylcholine
Draw the pathway for phospholipid synthesis
1 G-3-P + RCO-CoA to R’CO-CoA to phosphatidate and CoA to CDP-diacylglycerol using CTP and releasing PPi to phosphatidyl inositol using inositol and producing CMP
Mechanism II uses a head group (Serine) that reacts with CTP to form CDP-serine then that reacts with diacylglycerol
What is the role of phospholipase A2?
It cleaves a C2 fatty acid (that tends to be unsaturated like arachidonate) by phospholipase A2 for prostaglandin synthesis
What are sphingolipids used for?
They are important for myeline sheaths on nerve cells and they are the antigenic determinants for the ABO blood group
How are sphingolipids formed?
serine and palmitoyl CoA created a sphingosine, which creates ceramid through the addition of fatty acyl to an amino group. Ceramide is converted to sphingomyelin using phosphatidyl choline, which produces diacylglycerol.
Gangliosides and cerebrosides have sugar head groups on ceremide
Gangliosides and cerebrosides have _____. (during sphingolipid production)
Sugar head groups on ceremide
