Term
| The major functions of lipids are: a) as ___ and ___(i.e. acylglycerols and fatty acids). b) as structural components of ___ (e.g. phospholipids and cholesterol) c) as ___ molecules regulating cell growth, differentiation and metabolism. They also serve |
|
Definition
| storage forms and sources of metabolic energy; cell membranes; signaling |
|
|
Term
| Fatty acids are long-chain ___ with a ___ group at one end. Fatty acids, therefore, have a ___ and a ___ and are considered amphipathic. |
|
Definition
| hydrocarbons; OH; polar; hydrophilic portion |
|
|
Term
| Naming fatty acids: ∆ system- counts double bond positions from the ___, while the ω or n system – counts double bonds from the end of the fatty acid. |
|
Definition
|
|
Term
| acylglycerols: these are ___ of glycerol. Monoesters are called monoglycerides, diesters, diglycerides, triesters, triglycerides. |
|
Definition
|
|
Term
| Digestion begins in the stomach where acid-stable lipase produces a low level hydrolysis of triglycerides to ___, ___, and ___ (the ___ lipids which form an emulsion) |
|
Definition
| fatty acids, mono and diglycerides; amphipathic |
|
|
Term
| the micelle is made up of the following:(5)... |
|
Definition
| Bile Salt; Chol; Phosopholipids; Monacylglycerol; Lysolecithin |
|
|
Term
| reduction in bile acid secretion is referred to as ___ and always adversely affects intestinal absorption of lipids |
|
Definition
|
|
Term
| Cholestasis is cause by, among other things, congenital deficiencies in canalicular bile transporters such as ___, ___, ___, ; pregnancy, which is ___ induced; a congenital cholestasis accompanied by hyperbilirubinemia known as ___ syndrome; general ___ i |
|
Definition
| SPGP; MDR3; PFIC1; Dubin-Johnson; hepatic |
|
|
Term
| Triglyceride in the presence of ___ and ___ produce 2-monoacylglycerol and fatty acids |
|
Definition
| pancreatic lipase; colipase(which is activated from zymogen form by trypsin) |
|
|
Term
| ___ and ___ are pancreatic enzymes that require bile acid for activity |
|
Definition
| lipid esterase, phospholipase |
|
|
Term
| In cystic fibrosis, the pancreas is one of the affected organs, and in particular, the secretion of ___. This can be treated by nutritional supplementation with ___ and ___. |
|
Definition
| pancreatic lipase; recombinant pancreatic lipase; ursodeoxycholate |
|
|
Term
| The three hydrolytic products: ___, ___, and ___, unlike the neutral dietary lipids, triglycerides and cholesterol ester, are soluble in water which permits them to passively diffuse from the ___ to the surface of the intestinal microvillus where their li |
|
Definition
| fatty acids, 2-monoacylglycerols, and cholesterol; intestinal mixed micelle; intestinal epith cell |
|
|
Term
| Once absorbed into the intestinal epithelial cells, these lipids enter metabolic pathways which lead to formation of ___. These lipoproteins act to transport the dietary lipids to the ___ where they are metabolized further. |
|
Definition
|
|
Term
| To activate the absorbed fatty acids for resynthesis into acylglycerides, they are transformed into their ___ through the action of an enzyme called ___ (___). |
|
Definition
| acyl-CoA thioesters; acyl-CoA synthetase (thiokinase) |
|
|
Term
| The chylomicron(a type of lipoprotein) is composed of the following components: (4) |
|
Definition
Phospholipid, Cholesterol,
Cholesterol ester,
Triglyceride |
|
|
Term
| Lipoprotein fxn: chylomyicron fxns in transport of ___ and is unique in that is contains ___; VLDL fxns in ___; LDL fxns in ___; HDL fxns in ___. |
|
Definition
| lipids from small bowel; apoB48; lipid transport from liver; cholesterol transport into cells; cholesterol transport out of cells |
|
|
Term
| Dietary lipid provides substrates for the synthesis of the lipid component of ___ which are then transported through first the ___ and then the blood to its eventual destination: ___. |
|
Definition
| chylomicrons; lymphatic system ;the liver |
|
|
Term
| Chylomicrons are a member of the class of molecules called ___. |
|
Definition
|
|
Term
| The triglycerides are assembled into the nascent chylomicron particle in the ___- a process mediated by a lipid carrier protein called ___ , which is missing in a disease called ___ which results in severe malabsorption of triacylglycerol and fat soluble |
|
Definition
| endoplasmic reticulum; MTP9(microsomal triglyceride transfer protein); abetalipoproteinemia |
|
|
Term
| The apoliporotein component of the chylomicron is called ___ and it is synthesized posttranslationally by ___ from ___ which is the major component of the liver synthesized lipoprotein VLDL. |
|
Definition
| apoB-48; RNA editing; ApoB-100 |
|
|
Term
| the reaction catalyzed by acetyl coenzyme A carboxylase is the formation of ___ from ___. which is the first committed step in fatty acid biosynthesis |
|
Definition
|
|
Term
| Insulin activates/deactivates ACC but the only clear mechanism is through ___. |
|
Definition
| activates; transcriptional control |
|
|
Term
| Active AMPK (produced from AMPKK which comes from ____ activate/deactivates ACC while protein phosphatase activates/deactivates ACC. |
|
Definition
| cAMP-dep prot kinase; deactivates; activates |
|
|
Term
| Glucagon treatment up-regulates/down-regulates AMP-activated protein kinase through activation of adenylate cyclase which activates/deactivates ACC. |
|
Definition
| up-regulates; deactivates |
|
|
Term
| This inactive protomer, ACC polymerizes in the presence of ___ to give rise to an enzymatically active/inactive filamentous protein. This is an allosteric effect of ___- i.e. it binds to a site other than the active site to affect the enzyme. The activat |
|
Definition
| citrate; active; citrate; ATP-citrate lysase |
|
|
Term
| Glucose catabolism produces the ___ from which is derived, through the de novo pathway, the FA components of the ___ and ___. |
|
Definition
| Acetyl CoA; triglyceride; phospholipid |
|
|
Term
This protein, ___, catalyzes conversion of acetyl CoA and malonyl
CoA to palmitate |
|
Definition
|
|
Term
| Acetyl CoA is the primer of the ___, with 2 carbon units being added as ___. The thioesterase that releases palmitate from the complex has a high degree of specificity for ___. |
|
Definition
| FA synthase; malonate; C16 |
|
|
Term
| What reactions occur during the conversion of palmitate to oleate? |
|
Definition
|
|
Term
| The linoleoyl CoA + ___ -> gamma-linoleoyl CoA + ___ (which causes elongation) + ___ ->-> ___. |
|
Definition
| delta-6 desaturase; malonyl; delta-5 desaturase; arachidonyl CoA (arachidonate is an important precursor to many signaling molecules) |
|
|
Term
| What are the two sources of the glycerol backbone in hepatic triacylglycerol biosynthesis? |
|
Definition
| Glycerol after activation by hepatic glycerol kinase, dihydroxyacetone phosphate (DHAP) from glycolysis. |
|
|
Term
| What are the two major products of hepatic acyl glyceride synthesis? What is a common metabolic intermediate for both of them? |
|
Definition
| Triacylglycerol; Phosphatidyl-ethanolamine/choline; Diacylglycerol |
|
|
Term
| the two major pathways of hepatic phosphatidyl choline biosynthesis: the first is a tissue/non-tissue specific pathway with ___ as the controlling enzyme; the second pathway (required for synth of ___) is liver/non-liver specific and produces PC by methyl |
|
Definition
| non-tissue; cytidylyl transferase; liver; VLDL; S-adenosyl methionine(SAM) |
|
|
Term
| VLDL (its fxn is transport of lipid from ___) consists of ___ along with the ___. |
|
Definition
| hepatocytes; apoliproteins; lipids |
|
|
Term
| VLDL secretion into the blood is regulated by the rate of ___ synthesis. As for the intestine, the protein co-factor which acts to assemble triglyceride with VLDL is ___. |
|
Definition
| triglyceride; microsomal triglyceride transfer protein (MTP) |
|
|
Term
| Inhibition of Carnitine Palmitoyl Transferase (CPT I) is by ___ which causes stimulation/inhibition of hepatic lipogenesis. |
|
Definition
|
|
Term
| AMPK activation leads to increased fatty acid ___. |
|
Definition
|
|
Term
| Chylomicrons and VLDL are progressively degraded in the capillary beds of tissues such as muscle and adipose tissue, through the action of a trigylceride hydrolyzing enzyme called ___. |
|
Definition
|
|
Term
| Lipoprotein lipase is synthesized in ___ and ___ and secreted into the circulation. It is anchored at the ___ by polysaccharride chains. |
|
Definition
| liver; adipocytes; capillary endothelium |
|
|
Term
| The major site of remnant clearance is the ___. |
|
Definition
|
|
Term
Insulin is the key positive/negative regulator of hormone sensitive ___
by lowering cAMP levels and activating a lipase phosphatase. Insulin mediates
these effects through inhibition of ___ and activation of ___. |
|
Definition
| negative; lipase; adenylate cyclase; cAMP phosphodiesterase. |
|
|
Term
| With insulin resistance Type ___ diabetes, incr ___ occurs because VLDL, chylomicrons can not be taken up by ___. |
|
Definition
| II; tryglyceride; adipocyte |
|
|
Term
| An important malfunction of adipocyte is constitutive activity of ___ and, therefore, a high post-prandial release of ___. |
|
Definition
| hormone sensitive lipase; free fatty acids |
|
|
Term
| Higher levels of free fatty acids in the circulation are important contributors to insulin resistance in ___ and ___. |
|
Definition
|
|
Term
| ___ antagonizes insulin-receptor mediated trans- membrane signaling. |
|
Definition
|
|
Term
| TNF-α blocks insulin-stimulated phosphorylation of the insulin receptor by signaling ___ of the insulin receptor substrate. Serine-threonine phosphorylated IRS-1 has been shown to be an inhibitor of ___ tyrosine auto-phosphorylation. |
|
Definition
| serine-phosphorylation; Insulin receptor (IR) |
|
|
Term
| ___ is a hormone -produced in adipocytes-the level of its expression increases/decreases in response to increases in adipocyte mass. It acts on the hypothalamus as a satiety signal-thought to be regulator of fat storage homeostasis. |
|
Definition
|
|
Term
| in humans there are high circulating levels of leptin in ___, suggesting that obesity may represent a state of leptin resistance. |
|
Definition
|
|
Term
| What is the metabolic product of hormone sensitive lipase? How does it help maintain whole body energy homeostasis? |
|
Definition
|
|
Term
| What’s the mechanistic difference between insulin regulation of gluconeogenesis and lipogenesis in liver? |
|
Definition
| lipogenesis in liver has a transcriptional component |
|
|
Term
| ___ is a TF found in lipogenic genes. |
|
Definition
|
|
Term
| SREBP1 is/is not expressed in liver, and is/ is not expressed in adipocytes; this is the main basis for the ___. |
|
Definition
| is; is not; hypertriglyceridemia |
|
|
Term
| What process, normally up-regulated by insulin in liver, remains active during Type 2 diabetes? |
|
Definition
| liver triacylglycerol synthesis |
|
|
Term
| a loss of activity of SREBP1 in adipose tissue, coupled with retention of hepatic SREBP1 activity occurs in a condition called ___ in which there is a failure to form ___. |
|
Definition
| lipodystrophy; mature adipocytes |
|
|
Term
| ___ antagonizes insulin-receptor mediated trans- membrane signaling. In animal models of type 2 diabetes, antagonists of ___, or its receptor, clearly increase insulin sensitivity. |
|
Definition
|
|
Term
| ___ antagonizes the effects of TNFα and activates AMP dependent protein kinase, thereby stimulating both glucose utilization and fatty acid β-oxidation in muscle and liver through lowering ___ levels |
|
Definition
|
|
Term
| adiponectin lowers both ___ and ___ levels and it incr ___ sensitivity. |
|
Definition
| serum glucose; triglyceride; insulin |
|
|
Term
| What is the target of thiazolidinediones? Are they useful in the treatment of Type 2 diabetes produced by lipodystrophy? |
|
Definition
|
|
Term
| Choline in the presence of ___ -> phosphocholine which in the presence of ___ -> CDP-Choline which combines w/ ___ -> ___. |
|
Definition
| choline kinase; cytidyl transferase; diacylglycerol; phosphatidylcholine |
|
|
Term
| What is lung surfactant and what is the most common clinical presentation of a deficit in its synthesis? |
|
Definition
| DPPC (a phosphoglyceride); preemie babies |
|
|
Term
| What enzyme of DPPC synthesis is not required for the synthesis of other molecular species of PC? |
|
Definition
|
|
Term
| What is the main difference in the biosynthetic pathways leading to PC and PE, compared to those leading to PI, PG and CL? |
|
Definition
| Note the role of CDP-diacylglycerol in the PI, PG and CL pathways. |
|
|
Term
| What is the first step of ceramide synthesis? |
|
Definition
| 1)Condensation of palmitoyl CoA and serine to form 3-ketodihydrosphingosine (3-ketosphinganine) |
|
|
Term
| Ceramide is a precursor for what three major classes of sphingolipids? |
|
Definition
| Glycosphingolipids; sphingolipids; phospholipids |
|
|
Term
| What is a sphingolipidosis? Name two. |
|
Definition
| deficiency of ganglioside degradation enzymes; Tay-Sach's, Adult-onset Gaucher's |
|
|
Term
| What is the ganglioside to which cholera toxin binds? |
|
Definition
| Gm1 on intestinal mucosal cells. |
|
|
Term
| What are the two distinguishing structural characteristics of PAF? |
|
Definition
| Note the two unusual structural features: the ether linkage at sn-1 and the acetyl group at sn-2. |
|
|
Term
| What are the two major synthetic routes that release arachidonate from phospholipids? |
|
Definition
Arachidonate release from phospholipids occurs either through the
action of phospholipase A2 or
the sequential action of phospholipase C and a diacylglycerol lipase |
|
|
Term
| What are the three major oxidative fates of arachidonate? |
|
Definition
| PGH2; HPETE'S; Epoxyeicosatrienoic acids |
|
|
Term
| What are the functional differences between COX-1 and COX-2? Which of these should be inhibited to prevent thrombus formation? Which should be inhibited to treat chronic arthritis? |
|
Definition
| The cyclooxygenase responsible for synthesis of PGH2 in platlets (COX-1) is present constutively. In the inflammatory response of monocycte- macrophage the cyclooxygenase, COX-2, is transcriptionally induced by inflammatory activators, such as lipopolysaccharide and IL-1. |
|
|
Term
| What is the major cellular site of action of most prostaglandins? |
|
Definition
|
|
Term
| What is the mechanism of action of PGJ2? |
|
Definition
| PGJ2 arises from PGD2. The conversion of PGD2 to PGJ2 may not always be enzymatic. In macrophage, ∆12-PGJ2 has an anti-inflammatory effect mediated by PPARγ but also eventually induces apoptosis in these cells. Macrophage have been shown to be competent for synthesis of PGD2. ∆12-PGJ2 has the same effects on adipocytes as TZDs and has been suggested to be the natural homologue of the TZDs. |
|
|
Term
| Low dose aspirin is useful in the prevention of clotting mediated by which eicosanoid? |
|
Definition
|
|
Term
| Name a biologically active product derived through 5-lipoxygenase. What is its significance in asthma? |
|
Definition
| The biological significance of conversion of HPETEs to leukotrienes is better appreciated. Unlike the other eicosanoids the leukotrienes are relatively stable and persist for a hours in tissue. LTC4, LTD4 and LTE4 comprise the slow-reacting substance of anaphylaxis. They cause slowly evolving but protracted contraction of the smooth muscles in the airways and in the gastrointestinal tract. |
|
|
Term
| What are three major classes of lipid signaling molecules that arise from phosphatidyl inositol (PI)? |
|
Definition
|
|
Term
| What is the most common source of ceramide in transmembrane signaling? |
|
Definition
| lysosomal hydrolysis of sphingomyelin by sphingomyelinase. |
|
|
Term
| TNF-α induces ___ in a number of cell types through elevation of ceramide levels and has been reported to be a mediator in both these processes. |
|
Definition
|
|
Term
| What two signaling lipids can be formed through the action of phospholipase D? |
|
Definition
|
|
