Biochem Exam 3

major functions of lipids

energy storage (fully reduced so oxidize easily), membrane, wax, detergents, vitamins, coenzymes, hormones, messengers, electron carriers, pigments

basic structure of fatty acids

hydrophilic carboxyl head group and hydrophobic hydrocarbon chain, double bond (usually cis) when unsaturated

palmitic acid

16 C

stearic acid

18 C

palmitoleic acid

16 C with double bond

oleic acid

18 C with double bond

linoleic acid

18 C with 2 double bonds

alpha-linolenic acid

18 C with 3 double bonds

basic structure of wax

two fatty acids with ester linkage

structure and function of triacylglycerols

3 fatty acids in ester linkage with glycerol, neutral and used for storage

when fatty acids most energetically favorable, why

best when clustered together, H2O doesn’t need to form shell around it so entropy is increased

structure of glycerophospholipids

saturated on C1, unsaturated on C2, PO4- and some group on C3

phosphatidic acid

glycerophospholipids with H as group

phosphatidylethanolamine

glycerophospholipids with CH2-CH2-NH3+ group

phosphatidylcholine

glycerophospholipids with CH2-CH2-N+(CH3)3 group

phosphatidylserine

glycerophospholipids with CH2-CH-(COO-)(NH3+) group

phosphatidylglycerol

glycerophospholipids with CH2-CH-(OH)(CH2-OH) group

phosphatidylinositol 4,5-bisphosphate

glycerophospholipids with glucose (P attached to O on C4 and C5)

cardiolipin

glycerophospholipids with 2 glycerol groups (2 more additional fatty acids)

basic structure of ether lipids

fatty acid attached to C1 with ether linkage (no C=O), C2 is ester linkage, C3 is PO4- with random group

basic structure of sphingolipids

sphingosine with fatty acid on C2 and random group of C3

where different phospholipases cleave

A1 cuts ester linkage on C1, A2 cuts ester linkage on C2, C cuts after CH2-O on C3, D cuts between P and attached O-random group

significance of phosphatidylinositol 4,5-bisphosphate

source of intracellular signals, cut by hormone-sensitive phospholipase C in membrane into IP3 (Ca2+ entry) and diacylglycerol (activates protein kinase C)

basic structure of sterols and cholesterol

17 C in 4 rings, different side chains attached (alkyl side chain for cholesterol)

cholesterol at different temperatures

high temp - raises membrane melting point, stabilizes

low temp - prevents ordered packing, increase fluidity

isoprenoid compounds are, ex

derived from isoprene (draw it)

ex vitamins and sterols

bilayer permeable to

nonpolar lipophilic drugs, O2, CO2

different enzymes that flips fatty acids across bilayer

flippase - outside to inside, uses ATP

floppase - inside to outside, uses ATP

scramblase - swaps inside and outside

basic trend for melting point of different fatty acids

high melting point when saturated and long, low when lots of double bonds (effect of double bond > length)

membrane composition when high temperature outside

longer, more saturated

types of membrane proteins based on location

integral when firmly associated, peripheral associate with membrane or protein by electrostatic or hydrogen bonds, lipid linked / GPI anchored are part of hydrophilic head

hydropathy plot used to

estimate how many times protein passes bilayer (remember glycine or proline disrupts alpha helix)

different transport types across membrane

simple, facilitated (down gradient), primary active (uses ATP), secondary active (driven by ions moving down gradient), ion channel, ionophore mediated (moves ions in like a vesicle thing)

significance of passive transport

lowers activation energy, transporter forms noncovalent interactions and replaces shell of water

glucose transport into erythrocytes is ex of

facilitated uniport, glucose binding/unbinding changes shape of transporter

facilitated transport shows

saturability and specificity

erythrocyte chloride-bicarbonate exchnage is ex of

facilitated antiport, maintains electrical charge while moving bicarbonate out and into lungs

Na+/K+ ATPase is ex of

primary active

glucose into intestinal epithelial cells is ex of

secondary active, glucose moves in with 2 Na+

how glycerol enters glycolytic pathway

glycerol → L glycerol 3-phosphate → dihydroxyacetone phosphate → D glyceraldehyde 3-phosphate

fatty acid must be _ first, how

activated

PPi kicked off and fatty acid attaches to AMP → AMP replaced by CoA-SH → fatty acyl-CoA

how fatty acyl-CoA moves into mitochondria

turned into acyl carnitine then transported, carnitine moves back to cytosol

significance of acyl carnitine formation step

rate limiting, inhibited by malonyl-CoA

4 steps of beta oxidation

double bond between C2 and C3 → alcohol on C3 → alcohol turned to C=O → CoA-SH attaches to C3 and C1 and C2 released as acetyl-CoA

significance of step 1 of beta oxidation

makes FADH2, similar to complex II and pumps 6 H+

beta oxidation of 16 C fatty acid makes, total ATP made

8 acetyl-CoA, 7 FADH2 (step 1), 7 NADH (step 3) -> 108 ATP

106 ATP made bc 2 equivalents used initially

why fatty acid better than glucose

makes more ATP per carbon than glucose, storage of glucose requires water

beta oxidation when double bond between C3 and C4

enoyl-CoA isomerase moves double bond to between C2 and C3

beta oxidation when double bond between C2 and C3 AND C4 and C5

2,4-dienoyl-CoA reductase uses NADPH to get rid of double bond and moves it to between C3 and C4 → enoyl-CoA isomerase

beta oxidation when odd number fatty acid

CO2 added to 3 C compound, converted to succinyl-CoA (fed to TCA cycle)

last step of odd numbered fatty acid pathway requires

coenzyme B12, crazy step that swaps group on one carbon with H on neighboring carbon

different fates for fatty acid after beta oxidation

acetyl-CoA can either be fed into TCA cycle or into ketogenesis when starving

3 types of ketone bodies

acetone, acetoacetate, D beta hydroxybutyrate

ketogenesis mechanism

2 acetyl-CoA → acetoacetyl-CoA → another acetyl-CoA added to form HMG-CoA → acetyl-CoA removed to form acetoacetate → can be converted to acetone or D beta hydroxybutyrate

catabolism of D beta hydroxybutyrate

D beta hydroxybutyrate → acetoacetate → acetoacetyl-CoA → 2 acetyl Co-A

why ketone body synthesis occurs when starving

more gluconeogenesis which means TCA intermediates are depleted → less TCA cycle so acetyl-CoA accumulates → ketone body synthesis

first step in fatty acid synthesis, how, ATP used

acetyl-CoA transported to cytosol

citrate is exported and then cleaved to acetyl-CoA and oxaloacetate → malate → back to mitochondria as malate or pyruvate (makes NADPH in cytosol) → malate or pyruvate back to oxaloacetate and then citrate in mitochondria

2 ATP used

commitment step in fatty acid synthesis

formation of malonyl-CoA from acetyl-CoA and CO2, by acetyl-CoA carboxylase

regulation of acetyl-CoA carboxylase

activated by insulin and citrate

inhibited by glucagon, epinephrine, palmitoyl-CoA

fatty acid synthesis carried out by

fatty acid synthase (7 active sites)

4 steps of fatty acid synthesis, redox thing used

two groups attach → C=O reduced to alcohol → water removed to form double bond → double bond reduced to single bond

2 NADPH used

where carbons for fatty acid comes from, how it binds to fatty acid synthase

first 2 C from acetyl-CoA and rest from malonyl-CoA

forms ester bond to -SH group of 2 active sites

fatty acid synthase makes, requirement

palmitate (7 cycles, 16 C)

uses 21 ATP (3 per cycle, 2 for transportation, 1 by biotin) and 14 NADPH

how unsaturated fatty acid made from palmitate

by fatty acyl-CoA desaturase, uses electron transport chain where oxygen is electron acceptor and becomes water (H from NADPH)

fatty acid breakdown regulation

lipase - inhibited by insulin, activated by glucagon and epinephrine

how triacylglycerols and glycerophospholipids are synthesized

glucose and fructose -> L glycerol 3 phosphate -> phosphatidic acid -> triacylglycerol or glycerophospholipid

2 strategies to form phosphodiester bond between group and diacylglycerol

1\. activate phosphatidic acid with CDP → head group with alcohol attacks it → CMP off

2\. activate head group with CDP → attacks C3 with alcohol → CMP off

how sphingolipids made

palmitoyl CoA and decarboxylated serine combine → another fatty-acyl CoA added via amide bond → N-acylsphinganine → head group added

how spingomyelin made

N-acylsphinganine → head group added using UDP → double bond added

how cholesterol made

make mealonate (6 C) from ketone bodies (commitment step) → decarboxylation to make activated isoprene (5 C), 3 ATP used → make squalene (30 C) → cyclization to make cholesterol, catalyzed by cyclase

regulation of cholesterol metabolism

cholesterol synthesis - activated by insulin, inhibited by glucagon

cholesterol derivative inhibits synthesis and uptake of cholesterol into cells from diet

transamination by, how

aminotransferase that uses PLP

alpha-ketoglutarate gains NH3+ and becomes glutamate, amino acid loses NH3+ adn becomes alpha-keto acid

function of PLP

amino group carrier; mediates transamination, racemization, and decarboxylation

basic mechanism of transamination

forms keto acid first → reverse steps to transfer NH3+ to another alpha keto acid

how NH4+ transported to liver

glutamate can’t pass through membrane and NH4+ is toxic so transported via glutamine (back to glutamate in liver)

NH4+ transportation from active muscle

alanine used for transportation in active muscle, also replenishes glucose in liver, glutamate loses NH3 and becomes alpha-ketoglutarate, pyruvate gains NH3 and becomes alanine (back to glutamate in liver)

what happens to glutamate in liver, enzyme

turns to alpha-ketoglutarate, NADPH made, NH4+ released

by glutamate dehydrogenase

ways to excrete nitrogen

breath out for aquatic, urea (high water loss), uric acid for small animals

how NH3 enters urea cycle, enzyme

CPSI in mitochondria forms carbamoyl phosphate

ATP activates bicarbonate → NH3 replaces phosphate group → phosphorylated again

urea cycle

ornithine and carbamoyl phosphate form citrulline in mitochondria → citrulline moves out → combines with aspartate to form argininosuccinate → arginine and fumarate → arginine becomes urea and ornithine → ornithine back to mitochondria

aspartate argininosuccinate shunt

fumarate to malate which goes into mitochondria, oxaloacetate to aspartate which exits out, 4 ATP used per urea, NADH made

CPS I activated by, significance of these molecules

N-acetylglutamate (made from acetyl-CoA and glutamate, activated by arginine)

acetyl CoA - TCA slow, need alpha-ketoglutarate

glutamate - ammonia buildup

arginine - urea cycle intermediates are present

role of THF

one carbon transfer in intermediate oxidation states

role of AdoMet

one carbon transfer (CH3)

ketogenic aa that becomes acetyl-CoA

isoleucine, leucine, threonine, tryptophan

ketogenic aa that becomes acetoacetyl-CoA

leucine, lysine, phenylalanine, tryptophan, tyrosine

glucogenic aa that becomes pyruvate

alanine, cysteine, glycine, serine, threonine, tryptophan

glucogenic aa that becomes oxaloacetate

asparagine, aspartate

glucogenic aa that becomes fumarate

phenylalanine, tyrosine

glucogenic aa that becomes succinyl-CoA

isoleucine, methionine, threonine, valine

glucogenic aa that becomes alpha-ketoglutarate

arginine, glutamine, histidine, proline → glutamate

pyruvate from glucogenic aa

threonine → glycine → serine

tryptophan → alanine

serine, alanine, cystein directly becomes pyruvate

catabolic pathway for phenylalanine and tyrosine, unique

phenylalanine → tyrosine →→ both fumarate and precursor for acetoacetyl-CoA

difficult steps done by dioxygenase enzymes that use O2

diseases like PKU, tyrosinemia, alkaptonuria caused by

defects in Phe/Tyr metabolism enzymes, buildup of intermediates

catabolic pathway for valine, isoleucine, leucine

all become different alpha-keto acids → acyl-CoA derivatives → succinyl CoA, acetoacyl0CoA, acetyl-CoA

catabolic pathway for asparagine and aspartate

asparagine → aspartate → oxaloacetate

how NH3 added to molecules

through glutamate and glutamine, by glutamine synthetase (uses ATP) then glutamine amidotransferase

glutamine synthetase inhibited by

amino acids, AMP, carbamoyl phosphate

covalent modification - more active at high alpha-ketoglutarate and ATP, less active at high glutamine and Pi

how nitrogen transferred to -OH compounds

by glutamine amidotransferase, glutamine becomes glutamate

essential amino acids are, ex

can’t be made in body, must be obtained from diet

methionine, threonine, lysine, valine, leucine, isoleucine, tryptophan, phenylalanine, tyrosine, histidine