Oregon State BB 451 Midterm 2

Phosphatide

not a major membrane lipid but is an intermediate in the biosynthesis of other phosphoglycerides

essential fatty acids

fatty acids with a double bond past Delta9

Attachments to Phosphatides to form the major phosphoglycerides

choline, ethanolamine, inositol, serine

Cardiolipin

peripheral protein on inner mitochondrial membrane, attached to cytochrome c, aids in apoptosis

sphingolipids

two fatty acids, one polar tail

sphingomeylin

sphingolipid attached to phosphocholine (is the backbone) and uses the long hydrophobic amino alcohol sphingosine rather than glycerol as the platform

cerebroside (glycolipid)

sphingolipid attached to one simple sugar (contains monosaccharide)

ganglioside (glycolipid)

sphingolipid attached to complex carbohydrate (contain branched chains of multiple sugar subunits)

cholesterol

found in membranes, precursor to steroid hormones and bile acids

effects of cholesterol on the membrane

increases the range of fluidity (i.e. starts liquifying sooner and becomes fully liquid later) by disrupting the tight packing of fatty acid chains

Vitamin A

Retinol: storage

Retinal: vision

11-cis form -> all-trans form -> vision

Vitamin D

deficiency in childhood caused rickets, in adulthood causes osteomalacia (softening and weakening of the bones)

(phosphate absorption/metabolism, synthesis requires UV light)

Vitamin E

antioxidant used to break down reactive oxygen molecules

Vitamin K

blood clotting

Lipid Bilayer basics

polar outside, non polar inside, made of glycerophospholipids and sphingolipids

enzymes for transverse movement in bilayer

flippase, floppase, scramblase

flippase

movement outside to in (flip out)

floppase

movement inside to out

scramblase

movement out to in and in to out

Fluidity of membrane

based on saturating/length of fatty acids, cholesterol widens range of fluidity

four membrane permeable compounds

water, carbon dioxide, carbon monoxide, oxygen

four types of membrane proteins

integral, peripheral, anchored, associated

Membrane transport types

Uniport, Synport, Antiport

Uniport

moves one chemical one direction

Synport

moves one or more chemicals one direction

Antiport

moves one or more chemical opposite directions

Two ways to synthesize glycerophospholipids

1) activation of diacylglycerol (putting it onto an add-on)

2) activation of add-on (putting it onto a diacylglycerol)

Sphingolipid Synthesis

serine + palmitoyl-CoA -> intermediates -> dihydrosphingosine (one fatty acid tail)

Ceramide synthesis

dihydrosphingosine with another added fatty acid tail

Sphingolipid breakdown

complex process, can cause serious disease if inhibited

synthesis of cholesterol

IPP and DMAPP -> Geranyl-PP (10C)

Gernayl-PP + IPP -> Feransyl-PP (15C)

Feransyl-PP -> Squalene (30C)

Squalene -> Lanestrol

Lanestrol -> 19 steps -> Cholesterol

What are four roles of lipids?

1. simple lipids form fat globules for chemical energy storage

2.Phospholipids and glycolipids form membranes (lipid bilayers)

3.Help proteins anchor to membranes

4.Serve as a signaling molecule

what are the three types of TRANS unsaturated fatty acids?

elaidic, vaccenic, and linoelaidic acid

What type of bond connects the glycerol backbone to the fatty acids? (structure of fats/oils)

ester bonds

Phosphoglycerides

most abundant membrane lipids

what is phosphoglycerides composed of?

a glycerol platform esterfied to two fatty acids and a phosphate (or phosphate and alcohol)

glycolipids

shingosine platform and N-linked fatty acid, hydroxyl group is ether-linked to one or more sugars

micelle fatty acid (amphipathic)

has a monolayer structure with a solid core (diameter is constrained)

consequences of hydrophobic interactions

-lipid bilayers have an intrinsic tendency to be extensive

-lip bilayers tend to close on themselves

-lip bilayers are self self-sealing

lipid vesicles or liposomes

a spherical bilayer that is spontaneously formed from phospholipids and glycolipids

equation for determining number of molecules trapped in liposomes

volume (4/3 pi r^3) x molar (M) x Avogadro's number (6.02x10^23)

peripheral proteins

protein that can be extracted from membranes using mild conditions (such as salt extraction); (associate with membranes through integral proteins)

integral protein

proteins that can be extracted only by using detergents (usually span the lipid bilayer)

Bacteriorhodopsin

seven transmembrane domain proteins are common and include the G-protein-coupled receptor that mediate the "fight or flight" response to epinephrine

Alpha helical membrane-spanning regions

1. seven transmembrane domain proteins (bacteriorhodopsin)

2. single transmembrane domain proteins (glycophorin)

Beta barrel membrane-spanning structures

hydrophilic residues point inward (channel side) and hydrophobic residues outward (membrane side)

Prostaglandin H2 synthase

integral protein that does not fully span the lipid bilayer (made from arachidonate and is inhibited by aspirin)

Ras

a g-protein that is anchored to membranes by lipid attachments (hydrophobic anchors)

Unsaturations

cause kinks in hydrophobic tails (increases fluidity)

How many kcal/gram does complete oxidation of fatty acids and carbohydrates yield?

fatty acids: 9 kcal/gram

carbohydrates: 4 kcal/gram

chylomicrons

the class of lipoproteins that transport lipids from the intestinal cells to the rest of the body (goes to lymphatic system)

why are lipids always transported as lipoprotein complexes in the blood?

free lipids would otherwise form artery-clogging fat globules in the aqueous environment of blood

types of lipoproteins

-Very low density lipoprotein (VLDL)

-Low density lipoprotein (LDL-bad cholesterol)

-Intermediate Density lipoprotein (IDL)

-High density lipoprotein (HDL-good cholesterol)

HDL

carry lipids from the tissues from other tissues to the liver

VLDL

carry lipids from the liver to other tissues

IDL & LDL

taken up by the liver and other cells with LDL receptors

which hormones stimulate and inhibit fatty acid release from fat cells?

s- epinephrine and glucagon

i-insulin

What are the four steps of fatty acid beta oxidation?

1.oxidation by DAD

2. hydration

3. oxidation by NAD+

4.thiolysis by CoA

(removes 2 carbons each cycle and occurs on the beta carbon)

fatty acid oxidation

a chain of methylene groups is converted into activated acetyl groups

fatty acid synthesis

activated acyl groups and malignly groups are converted into a chain of methylene groups

What are the four steps of fatty acid synthesis?

1.joining reaction

2.reduction

3.loss of water

4.reduction

(add 2 carbons at each step)

fatty acid degradation

catabolized by acyl-CoA synthetase in the mitochondria

synthetases

enzymes that is the energy of ATP hydrolysis to make larger molecules form smaller molecules

Outputs for each fatty acid beta oxidation cycle is one molecule of:

FADH2

NADH + H+

acetyl-CoA

acyl-CoA (shortened by 2 carbon residues)

First reaction:

oxidation of acyl-CoA by acyl CoA dehydrogenase to generate trans-delta2-enoyl-CoA (FAD is the electron acceptor)

Second reaction:

hydration of enoyl CoA by enoyl CoA hydratase producing L-3-Hydroxyacyl-CoA

Third reaction:

oxidation of C3 carbon by hydroxyacyl-CoA-Dehydrogenase to produce 3-Ketoacyl-CoA (NAD+ is the electro acceptor)

Fourth Reaction:

cleavage of ketoacyl CoA by Beta-ketothiolase to produce Acyl-CoA and Acetyl-CoA

oxidation of unsaturated fatty acids

-required additional enzymes to move a double bond (cis-delta3-enoyl CoA)

-the first oxidation reaction is bypassed so FADH2 is not generated

-yield less energy per molecule

ATP yields of:

FADH2

NADH

GTP

FADH2=1.5

NADH=2.5

GTP=1

Products for each acetyl-CoA

3 NADH

1 FADH2

1 GTP

oxidation of fatty acids containing odd # of carbons

-the final round of degradation results in one molecule of acetyl-CoA and one molecule of propionyl CoA that is converted to saucily CoA before entering CAC

Peroxisomal fatty acid oxidation vs mitochondrial beta oxidation

1. activated acyl chains are shortened to 8 carbons

2.rather than entering the ETS, electrons from the first oxidation reaction are transferred to )2 and generate H2O2

how is peroxisomal oxidation induced and why is it important?

-by a high-fat diet

-required for normal brain development and function, and formation of myelin

what syndrome is due to the absence of functional peroxisomes, resulting in death?

Zellweger Syndrome

when there is excess acetyl CoA, what is it converted to and the advantage of that?

converted to ketone bodies that is soluble in aqueous solution

how is acetoacetate activated?

it is activated by transfer of CoA from succinyl CoA to Acetoacetate then is converted to two acetyl CoA by thiolase

elongation reactions of fatty acid synthase

1.condensation

2.reduction

3.dehydration

4.second reduction

phosphatidate synthesis

two activated fatty acids (acyl CoA) are esterfied to hydroxyl groups of glycerol phosphate to form phosphatidate

triacylglycerol synthesis

phosphatidate is hydrolyzed to DAG then the third fatty acid is added using acyl-CoA to form triacylglycerol

phosphoglyceride synthesis

involves a CDP-activated intermediate that is formed either by diaclyglycerol or the alcohol being activated

phospholipid synthesis from an activated diaclyglycerol

phosphotidate reacts with CTP to form an activated intermediate (CDP-Diacylglycerol) with a reactive phosphoanydride bond which then reacts with the alcohol to form a phospholipid

phospholipid synthesis from an activated alcohol

the alcohol reacts with ATP to form an intermediate with a phosphoester bond then reacts with CTP to form an activated intermediate with a reactive phosphoanydride bond then is cleaved when reacted with diaclyglycerol to form the phosphoglyceride

what are the five staged of cholesterol synthesis?

1. synthesis of 6-carbon molecule (mevalonate) from acetyl CoA

2.conversion of mevalonate to activated 5-carbon isoprene building blocks (isopentenyl pyrophosphate and dimethyllallyl pyrophosphate)

3.condensation of activated isoprene building blocks to sequentially form a 1- carbon (geranyl), 15 carbon (farnesyl), and 30 carbon (squalene) intermediates

4.cyclization of squalene to form a steroid (ianosterol)

5.conversion of ianosterol to cholesterol

synthesis of bile acids

addition of acidic groups gives the molecule soap-like properties that allows it to emulsify dietary lipids

synthesis of cholesterol esters

esterification of fatty acids to the cholesterol hydroxyl group eliminates the amphipathic nature of cholesterol and forms the solid core of lipoprotein particles such as LDL

inorganic forms of nitrogen

glutamate, glutamine, and carbamoyl phosphate

what are the two enzymes to reduce nitrate to ammonia

1.nitrate reductase (uses NADH and NADPH as reductant)

2.nitrite reductase (uses ferredoxin as reductant)

glutamate synthesis

-catalyzed by glutamate dehydrogenase

-does not involve ATP hydrolysis; NADPH oxidation drives the reaction

-enzyme holds substrates such that only L stereoisomer of glutamate is synthesized

glutamine synthesis

-catalyzed by glutamine synthetase

-involves generation of a phosphoryl intermediate with reactive anhydride bond

carbamoyl phosphate synthesis

-catalyzed by carbamoyl phosphate synthetase