biochem Flashcards
glycolysis production phase
G3P is ox by G3P dehydrogenase to 1,3 BPG
then PEP to pyruvate using #pyruvate kinase
** fructose 1,6 bisphosphate upregulates this, downregulated by ATP
- this one is irreversible
- made 2 ATP and NADH per pyruvate
G6P fates
- glycolysis (glucagon), PPP or glycogenesis (insulin)
- can only be undone to glucose by liver and kidneys
fates of pyruvate
- converted into acetyl coa by #pyruvate dehydrogenase
- oxaloacetate by pyruvate carboxylase
- lactate using lactate dehydrogenase
PPP irreversible ox phase (RLS?)
- makes 2 NADH ribulose 5 P
- G6P is turned into 6 phosphogluconolactone using glucose 6 P dehydrogenase RLS!!
- then 6 phosphogluconate makes ribulose 5 p using 6 phosphogluconate dehydrogenase
PPP non ox phase
- ribose 5 P makes fructose 6 p and G3P
- isomerase makes ribulose 5 p to ribose ( makes DNA)
- epimerase makes xyulose from ribulose
- transketolase transfers 2C from xyulose to ribose making sedahepulose and G3P
- transaldolase removes 3 C from sedaheptulose to make erythrose 4 P adding the last carbons to G3P making fructose 6 P
- if xs xyulose then transketolase transfers 3c from xyulose to erythrose making G3P and fructose 6 phosphate
– uses 3 ribulose!!!
gluconeogenesis
- *pyruvate in mito by pyruvate carboxylase turns to oxalo
- *then #phophoenol pyruvate carboxykinase makes PEP
- G3P made then turned to fructose 1,6 bisphosphate
- turns to fructose 6 P using fructose 1,6 bisphosphatase RLS!!!!
- limited by inuslin and on by glucagon
- then make gluc 6 phosphate to be turned to gluc in liver ER by phosphatase
**oxalo is diverted to form energy!
malate shuttle
transports oxalo across mito to cytosol using malate dehydrogenase in gluconeo
krebs
- # pyruvate dehydrogenase turns pyruvate to acetyl coa in mito
- *citrate synthetase adds it to oxalo (- reg by atp)
- RLS: isocitrate made then turns to a keto glu using isocitrate dehydrogenase (- by ATP, NADH, + by ca)
- *a keto glu turns to succinyl coa by a keto glu dehydrogenase (- by nadh, succinyl coa and atp)
- succinyl coa to succinate = GTP using succinate thiokinase
- succinate makes fumerate using succinate dehydrogenase (FADH!!!)
- malate to oxalo by malate dehydrogenase
**energy made is through substrate level phos
atp synthase structure
- f1 faces the matrix (all the a,b units)
- f0 faces intermem space with all the c1s
- upreg by adp leading to more ox consumption leading to more stim of TCA to make NADH!
anaerobic conditions
- make 2 atp and 2 lactic acid
chylomicrons
- only transport dietary fat
- not associate with fasting state
- structure is monophopholipid layer, cholesterol and TG core
- have apo b48 made in INTESTINE and allows secretion from SI!!!!!
- made in enterocyte ER, then nascent is TG rich. mature when its picked up APOc2 and ApoE from HDL
- apoc2 activates LIPOPROTEIN lipase in capillary then hydrolyze tag to FA
- remenant chylo is taken up by liver after losing apoc2 (but still apo E present E= exit thru liver)
- release TAG in enterocyte and lip sol vitamins
fa nomenclature
- first c is anomeric, last is omega
- shorthand: # of carbons: # of double bonds
- form micelles
- adding coa to fa activates it to stay in cell since hydrophilic
albumin
carries free fa that are less than 12c long
TAG, Bile things too
- usually the 2 c spot is where essential fa are! (unsat usually while the others are sat
- can’t cross enterocyte mem so must be broken down (esp if 12c+) by bile micelles
- bile recruits panc lipase to cleave at 3 and 1 pos (preserving essential FA!!). makes di glycerol then monoglycerol.
- but immediately after crossing SI mem, FA are esterified to glycerol to make TAG then make chylomicrons
omega FA
- essential fa are linoleate and linolenate since make C12 and 15 (we can’t do past 10)
- omega 3 and 6 are counted from the back end carbon!
- omega 6 is linoleic, 3 is linolenate
- high ratio of omega 3 to 6 is best
- 3 is anti inflam, 6 is pro
trans fat
- behave like saturated FA since can stack well
- worst fats mostly in margarine, dessert, creamer etc
- labels say 0 trans fat if less than 0.5!!! so serving add up
- 2 g per day increases cardio disease by 20%
olestra
- man made where fats are linked to sucrose backbone!! CAN’T BE DIGESTED so pooped out
- stop abs of fat sol vitamins
fat sol vitamins
- vit a, d, e, K
- stored in fat so can be toxic
- A can be made from diet
- vit D made from sterol. xs leads to kidney stones and weak muscles
- vit E diet is antiox and decreases cardio and cancer
- vit K diet and made is made for clotting
FA digestion
lingual lipase would digest fa less than 12 c. gives energy to mouth cells
gastric lipase does some TAG digestion in stomach
CCK made by small intestine to stim release of bile to emulsify fat also release panc enzymes like lipase, colipse, cholesterol esterase and phospholipase A2mi
- CCK also stim release of secretin that release bicarb to raise pH for optimum Digest in SI
Km and lipase
muscle: has high affinity low km so can take up free FA even when chylomicron is low. esp cardiac
adipocytes have high Km low affinity so only chylomicron take up for storage (in insulin)
* liver has high afffinity, low km
cholesterol esterase and phopholipase A2
- ester digests partially cholesterol in animal products
- A2 is for both animal and plant. cleavage at cc2 from phospholipid!!
how are fa moved from fat to blood
GPCR CAMP and PKA turn on hormone sensitive lipase and phosophorylates perilipin. perilipin breaks adipose shell so lipase can cleave tag to FFA and glycerol
- only RBC don’t have FA transporter (into cell)
FA oxidation
- activation by adding acyl coa using acyl coa synthetase. uses 2 ATP (diff for peroxisome and mito)
- enter into inner mito mem using carnitine by carnitine acyl transferase. (then removed using carnitine palmitoyl transferase) - by malonyl coa from FA synth
- palmitoyl coa gets dehydro using acyl coa dehydrogenase to make FADH2
- isomer by ADDING WATER HYDRATION
- dehydrogenation: make an NADH
- acyl coa acetyltransferase (THIOLASE) makes acetyl coa (2c) and acyl coa (that is 2C shorter) – by ATP, NADH, FADH, acetyl coa
** to use these acetyl coa, must have oxalo from pyruvate, this we need carbs!!!
of C and cycles of b ox
- if 14 c, then 6 cycles leads to 7 acetyl coas
- each cycle makes 1 NADH (2.5 ATP) and 1 FADH2 (1.5 ATP)
if 16 C then what is b ox yield
- 8 acetyl coa, 7 nadh, 7 fadh
AMPK
- activated by high AMP to upregulate catabolic process like fa ox, less gluconeo and downreg anabolic like fa, choles, and protein synth
- inhibit hmg coa reductase and decrease choles synth
- this is in the cytosol!!! whereas the NADH sensor are in mito
peroxisome
- 20c+ fa ox here
1. gives H2o2, not FADH like mito ox broken by catalase
5. dehydrogenation: make an NADH
4. acyl coa acetyltransferase (THIOLASE) makes acetyl coa (2c) and acyl coa (that is 2C shorter) – by ATP, NADH, FADH, acetyl coa
2. stops when reach 4-6 C then go to mito then do b ox using carnitine etc
FA ox disorders
- bad mito: means less energy so muscle breakdown, heart grows in size, less capacity to exercise. INCREASED acylcarnitines in blood
- primary/secondary carnitine def: can’t bring FA inside so same symptoms. secondary is caused by dialysis, AIDS
lipogenesis
- FA are made in liver CYTOSOL in fed state, but acetyls are made in mito. get NADPH from PPP and malic enzyme process
1. ***turn acetyl coa into malonyl using acetyl coa carboxylase and biotin (ATP) - by AMP, acetyl coa (to let fa enter mito) + by insulin, citrate - malonyl also inhibits carnitine palmitoyl transfase so no FA enter mito for ox!!
2. FAS: - condensation by adding acetyl to malonyl on ACP, then reduction by using NADPH, dehydration making double bond then reduction with NADPH to make it fully unsaturated
- grows 2 c at a time
3. palmitate is cleaved by thioesterase (16 C reached)
– needs 14 NADPH and 7 ATP
4. can be stored in adipose, made into phospholip, or packaged into VLDL
VLDL
- carries de novo synth FA!!
- has Apob100 from liver. its a ligand for LDL receptor and picks up apoc2 (activate LPL on capillary) and apo E from HDL
lipogenesis regulation using glucose pathways
more acetyl coa inhibits #pyruvate dehydrogenase (makes acetyl coa) and activates pyruvate carboxylase (makes oxalo)
- OAA condensing with acetyl to make citrate increases PDH activity and decrease PC
- when high flux of TCA leads to NADH, citrate is transported to cytosol!!
malic enzyme pathway
- when citrate booted to cytosol, we make NADH by turning it into OAA using citrate lyase (ATP) then malate using malate dehydrogenase and NADPH using malic enzyme
- back to pyruvate for TCA
FAS complex
- makes reaction faster, stops dilution of reactants, protect surface from competing rxns
- homodimer aligned antiparallel and 7 catalytic sites
- has ACP and CE, thioesterase, transferase
- malonyl always on ACP!!
where is biotin
in all carboxylases, even pyruvate carboxylase!
regulation of b ox
- AMPPK inhibits malonly coa (from fa synthesis) so it can make carnitine
- acetyl coa stops thiolase
regulation of acetyl coa carboxylase
- fa synth and makes malonyl coa
– by palmitoyl (0 feed) and AMPK
+ by citrate and insulin
also acyl coa stops it, allows fa to enter mito for ox
cholesterol
- can’t be broken down!! either made into esters, excreted, used to form bile, steroid hormones or vit d
- 4 rings
- low choles leads to alzhiemers, depression, memory loss, suicide and violent behavior
- made in liver (makes HIGH BMR!)
- 25% in brain
high cholesterol clinical
- xanthoma is where fats build up
- white eye patch
- hyperlipidemia in plasma and white ring around iris
choles uptake from diet
- enter enterocyte using neimann pick NPc1L1 protein using micelle
- esterified by ACAT then into chylomidron to lymph
OR comes back out of cell using ATP binding cassette ABCG5 and 8 (form sterolin complex) that couples ATP hydrolysis to transport choles back to lumen
cholesterol synthesis
- all cells do it, but mostly liver cytosol and ER
1. ***3 acetyl coa units via thiolase enzyme to make acetoacetyle coa - HMG coa synthase to make HMG Coa
**cytosol - HMGcoa reductase makes mevalonate and anchor to ER!!
2. polymerization of 6 5C isoprene units dephos and decarb - uses 3 ATP
3. head to tail condensation forms geranyl pyrophos then farnesyl (geranyl geranyl) to make squaline
3. cyclization of squaline to form sterol ring (irreverse) - lanosterol is first closed ring
statins
- block HMG Coa reductase so less choles made
- also block formation of geranyl and farnesyl which are needed to form lipid anchors on membranes
- also no formation of ubiquinone (CoQ) so less energy from ETC. need supplement
- no dolichol (for glycosylation of proteins)
- muscle weakness
- this also makes cells constantly need to pick up choles, so decrease xcell choles!!! good since take up LDL (and less ox time to make plaque)
fate of choles after synthesis
- added to plasma mem, esterified by ACAT to make choles ester (stored), transported in lipoproteins, precursor for other comps
- often contains linoleic!! can use this to store essential FA!!!
HMG coa reductase regulation
+ insulin
- glucagon, choles stim proteolysis of the enzyme!!! (- feed)
- THIS IS upreg BY glucagon STEROLS!! the proteolysis (this is longer term control)
- by AMPK
SREBP regulation
SREBP: sterol regulatory element binding protein increase anabolic process and synth of choles
- enhance HMGCOA transcription binding to reg element
- SREBP is bound to SCAP in ER when choles is high
- when low, SREBP: SCAP is transported into golgi, where proteolysis to release DNA binding domain
- binding domain activates SRE allowing transcription