Biochem Flashcards
GLUT 2 vs GLUT 4 compare and contrast
which tissues?
purpose?
Km and kinetics?
glucose uptake receptors- independant on Na+
Which tissues?
- GLUT 2= hepatocytes and pancreatic B (beta) islet cells
- GLUT 4= adipose tissue, muscle cells
Purpose:
-GLUT 2- picks up glucose after meal (high conc.) from hepatic portal vein so excess can be stored in liver. glucose [] below Km= enters peripheral circulation. Serves as glucose sensor for beta cells in pancreas- high glucose=insulin release
-GLUT 4- responsive to insulin. Stimulates movement of additional GLUT 4 to membrane via exocytosis so glucose from peripheral blood can be taken in. Muscle cells- glycogen. Adipose- glucose forms DHAP to form glycerol phosphate to store fatty acids as triacylglycerol
Kinetics/Km:
- GLUT 2= high Km= first order kinetics= glucose transport rate increases proportional to []. If glucose below Km- enters peripheral circulation
- GLUT 4= low Km close to normal glucose levels- gets saturated at slightly higher blood glucose levels= zero order kinetics- constant rate. Increase uptake of glucose with insulin- trigger more GLUT 4 to go to membrane
Hexokinase vs glucokinase
1st step of glycolysis- convert glucose to G6P to prevent it from leaving cell through transporter (specific). Requires ATP and Mg+2 as a cofactor!!!!! Kinases!
hexokinase- most tissues, low Km (saturated quickly, zero order), inhibited by G6P
glucokinase- only in liver and pancreatic B- islet cells, high Km (first order), induced by insulin in hepatocytes. Also acts as glucose sensor in B-cells along with GLUT 2
Rate limiting enzymes for: glycolysis fermentation glycogenesis glycogenolysis gluconeogenesis Pentose-Phosphate Pathway
glycolysis= phosphofructokinase 1 (PFK-1)
fermentation= lactate dehydrogenase
glycogenesis= glycogen synthase
glycogenolysis=glycogen phosphorylase
gluconeogenesis= fructose 1,6 bisphosphotase
Pentose-Phosphate= 6GP (glucose-6-phosphate) dehydrogenase
PFK 1 and PFK 2 aka Phosphofructokinases and what happens to fructose 1,6 biphosphate
please also describe regulation!!!!!
PFK 1:
F6P- fructose 6- phosphate is phosphorylated to fructose 1,6 biphosphate— requires ATP
F6P made from isomerase acting on G6P
Rate limiting step of glycolysis:
- inhibited by ATP, citrate
-activated by AMP, fructose 2, 6 biphoshpate (in liver)
fructose 1,6 biphosphate split by aldose in next step into two 3 carbon compounds- DHAP and glyceraldehyde 3-P
PFK 2:
- activated by insulin= converts F6P to fructose 2,6 biphosphate= activates PFK 1 in hepatocytes
- inhibited by glucagon—- leads to inhibition of PFK 1
- allows liver do glycolysis even when lots of ATP around for other processes
Glyceraldehyde 3-P dehydrogenase
adds phosphate to glyceraldehyde 3P and oxidizes it to become 1,3 bisphosphoglycerate (high energy). NADH made.
3-phosphoglycerate kinase
1,3 bisphoshoglycerate loses phospate, forming ATP and 3-phosphoglycerate—–substrate level phosphorylation
Pyruvate kinase+ feed forward activation
PEP- phosphoenolpyruvate (high energy) loses phosphate and becomes pyruvate= ADP to ATP!!!
activated by fructose 1,6 bisphosphate (product of PFK-1) —- feed forward activation
Fermentation process
Enzyme- lactate dehydrogenase
NADH to NAD+
pyruvate to lactate (3C)
poor oxygenation- anaerobic conditions
yeast- make ethanol (2C) and CO2 (1 C)
DHAP (two fates)
formed by aldose splitting fructose 1,6 bisphosphate.
- can be isomerized to glyceraldehyde 3P to continue glycolysis
- glycerol 3P dehydrogenase can be to convert DHAP to glycerol 3-P in liver and adipose tissue to form glycerol= triacylglycerols!
Irreversible enzymes of glycolysis
PFK-1, hexokinase/glucokinase, pyruvate kinase (all the kinases push forward the process)
High energy intermediates of glycolysis- make ATP
1,3 BPG (3-phosphoglycerate kinase), PEP (pyruvate kinase)
Red blood cells- glycolysis what is produced and what is its effect
1,3 BPG is converted to 2,3 BPG by bisphosphoglycerate mutase.
Allosteric effect on hemoglobin HbA- decreases affinity for O2= hemoglobin releases O2= delivered to tissues.
Curve shifts right- for same amount in blood (PO2) less bound to hemoglobin (less saturation)
doesn’t bind to fetal hemoglobin
hemoglobin abbreviation
HbA
Galactose metabolism
lactose splits into galactose and glucose (lactase brush enzyme)
- galactokinase converts it to galactose 1-P, using ATP (traps in cell)
- Gal-1-P-uridyltransferase and an epimerase converts galactose 1-P to glucose 1-P which can be used to make G6P or glycogen
excess galactose= galactitol in lens= cataracts in eye
Fructose metabolism
sucrose disaccharide splits into glucose and fructose by sucrase (brush enzyme)
fructose from honey, fruits, etc.
fructokinase converts to fructose 1- phopshate (traps in cell)
aldolase converts fructose 1P to DHAP and glyceraldehyde— becomes glyceraldehyde 3P
Pyruvate dehydrogenase complex (PDH)
- describe reversibility
- products of reaction
- regulation( inhibition and activation)
pyruvate (3C) to acetyl CoA (2C)
irreversible
NADH made and CoA added
CO2 released
inhibited by acetyl CoA, if enough acetyl CoA, pyruvate used to make oxaloacetate or fatty acids
insulin activates it in liver, whereas brain no hormones effect
Glycogen storage and purpose in its two locations
Stored in cytoplasm of liver and skeletal muscle cells as granules
protein cores
polyglucose chains coming off of the core
- linear= highest density near core
-branched= highest density near periphery for rapid release of glucose
purpose;
liver=maintain constant blood glucose levels
muscle= energy reserve
Glycogenesis- steps and all enzymes involved + describe RDS and control on enzymes
G6P converted to G1P.
G1P coupled with UDP= UDP-glucose (made by UTP and loss of two phosphate)
glycogen synthetase removed UDP and integrates the glucose into the glycogen chain by forming alpha 1-4 glycosidic bonds
branching enzyme- hydrolyzes 1,4 bond, transfers oligoglucose chain, and attaches it via alpha 1,6 linkage to make branch
glycogen synthetase= rate limiting step.
stimulated by insulin and G6P= insulin=more glucose storage
inhibited by epinephrine and glucagon= less glucose storage
Glycogenolysis
Rate limiting enzyme= glycogen phosphorylase
- —breaks alpha 1-4 glycosidic links, releasing G1P, which is converted to G6P
- –activated by glucagon in liver and activated by AMP and epinephrine in muscle
- –inhibited by ATP
- –can’t work on 1,6– need debranching enzyme
debranching enzyme:
-made up of two enzymes. One enzyme breaks 1-4 bond closest to branch and transfers sugar to end of open chain. Other enzyme releases one monomer of glucose by breaking 1-6 bond.
Glycogen storage diseases
accumulation of lack of glycogen in one or more tisses
enzymes can be affected- activity and isoform (diff. form of same protein)
Gluconeogenesis
location, purpose, control
Done in the liver (and kidneys)
Promoted by glucagon and epinephrine- raise blood sugar levels— especially during fasting when glycogen drops and no glucose source external!!!!!
only source of glucose after 24 hours (glycogen all gone)
inhibited by insulin
Pentose Phosphate pathway (PPP)/ Hexose Monophosphate shunt (HMP)
-location, purpose, control
Occurs in cytoplasm of all cells
- production of NADPH (2)
- source of ribose-5-phosphate for nucleotide synthesis
G6P oxidized to 6-phosphogluconate by G6P dehydrogenase, making NADPH. 6-phosphogluconate oxidized and decarboxylated to ribulose 5P. (NADPH made)
fructose 6P, glyceraldehyde and ribose 5P interconverted via intermediates—– done by TPP and transaldolase
rate limiting enzyme is glucose-6-phosphate dehydrogenase
activated by NADP+ and insulin!- anabolic
inhibited by NADPH
NADPH
not same as NADH
- acts as electron donor, reducing agent
- biosynthesis- fatty acids and cholestrol
- cellular bleach production in leukocytes- bactericidal
- protects cells from free radical oxidative damage caused by peroxides like H2O2 made during respiration—- glutathione is reducing agent that reverses radical formation and NADPH is used to maintain its supply
Steps of citric acid cycle- remember mnemonic, def. of flavoprotein.
Describe intermediates, enzymes, and what produced in each step please
Mnemonic for citric acid substrates: Please, Can I Keep Selling Seashells For Money, Officer?
P- pyruvate. Step 0= pyruvate to acetyl CoA- pyruvate dehydrogenase- NADH made. CO2 released
C- citrate (6C). Step 1= oxaloacetate (4C) and acetyl (2 C) CoA combine= citrate (6 C) and CoA- citrate synthetase
I-isocitrate (6C) Step 2= citrate isomerized to isocitrate via aconitase, requires Fe+2.
Remove water= cis-aconitate, and add water= isocitrate
K- alpha-ketoglutarate (5C). Step 3= isocitrate oxidized to oxalosuccinate by isocitrate dehydrogenase, forming NADH. Oxalosuccinate becomes alpha-ketoglutarate via a loss of CO2.
CO2 made, NADH made
S-succinyl CoA (4C). Step 4= alpha ketoglutarate dehydrogenase complex adds CoA, removes CO2, and oxidizes= NADH production.
CO2 made, NADH made
S- succinate (4C). Step 5= succinyl CoA- lose CoA and make succinate. GTP formation= direct ATP. Succinyl CoA synthetase (not synthase- require energy input to create bonds)
F- fumarate (4C). Step 6= oxidation of succinate by succinate dehydrogenase to make fumarate and FADH2 from FAD. Occurs on inner mitochondrial membrane.
Succinate dehydrogenase= flavoprotein= bonded to FAD
FADH2 passes electrons to ETC to make 1.5 ATP. Enzyme is part of complex 2 of ETC.
M- malate (4C). Step 7= fumarate to malate (alkene to alkane), requires water. — fumarase
O- oxaloacetate (4C) Step 8=malate dehydrogenase oxidizes malate to oxaloacetate. NADH formed.
Net results of citric acid cycle and glycolysis
pyruvate dehydrogenase complex= 1 NADH, 1 CO2
citric acid cycle= 3 NADH, 1 FADH2, 1 GTP, 2 CO2
4 NADH= 10 ATP (2.5 ATP each)
1 FADH2=1.5 ATP
1 GTP=1 ATP
12.5 ATP per pyruvate= 25 per glucose
dehydrogenase- formation of NADH/FADH2
glycolysis: 2 net ATP per glucose, 2 NADH made.
2.5*2=5+2=7
30-32 ATP?
Location and regulation/control of citric acid cycle
citrate synthetase- inhibited by ATP, NADH, succinyl CoA, citrate (allosteric)
isocitrate dehydrogenase- inhibited by ATP, NADH so stimulated by ADP, NAD+
alpha-ketoglutarate dehydrogenase complex- inhibited by ATP, NADH, and succinyl CoA (its product). Stimulated by Ca+2 and ADP.
both CO2 losses, and first step
Pyruvate dehydrogenase complex regulation
Phosphorylated= inactivated– done by pyruvate dehydrogenase kinase (high ATP)
Dephosphorylated= active– done by pyruvate dehydrogenase phosphatase (high ADP)
also inhibited by ATP, NADH, and acetyl CoA (which can be made from fat)
ETC- oxygen role
O2 has high reduction potential- good electron acceptor. Combines with electrons as H- to make H20.
Lipid mobilization from adipose tissue
HSL!!!! LPL
Postabsorptive state- falling insulin levels, like at night. Fatty acids are released from adipose tissue for energy
Low insulin/high epinephrine and cortisol= activate HSL= hormone sensitive lipase
Hydrolyzes triacylglycerol to glycerol (used in glycolysis/gluconeogenesis in liver when glucagon up) and fatty acids (B-oxidation in liver)
Need LPL- lipoprotein lipase to metabolize triacylglycerol in VLDL or chylomicrons into fatty acids and glycerol released into adipose/tissues
Lipid transport (free fatty acids vs cholesterol vs triacylglycerols)
Free fatty acids- transported in blood via albumin
Cholesterol and triglycerides= need lipoproteins
Lipoproteins
aggregates of apolipoproteins and lipids. Named according to protein density (more protein, less fat= high density)
HDL>LDL>IDL>VLDL>chylomicrons
Chylomicrons
transport dietary triacylglycerols, cholestrol, and cholesteryl esters in blood/lymph from intestines to adipose tissues and liver- assembly in intestines
VLDL
produced and assembled in liver- transport triacylglycerols and fatty acids from liver to tissues
liver assembles triacylglycerols
IDL
Remnants of VLDL from triacylglycerol removed from it.
Reasborbed by liver
Picks up cholesteryl esters from HDL to become LDL
transition between triacylglycerol transport and cholestrol transport
LDL
deliver cholesterol to tissues for biosynthesis and cell membranes (and also to make bile and hormones)
HDL
synthesized in liver and intestines.
- Cholesterol recovery- cleaning excess cholesterol from blood vessels for excretion!!!!!!!
- transfer apolipoproteins to other lipoproteins
- delivers cholesterol to steroidogenic tissues
Apoproteins/Apolipoproteins
receptor molecules- involved in signaling
apoA-1- activates LCAT for cholesterol esterification
apoB-48- chylomicron secretion
apoB-100- uptake of LDL by liver
apoC-2- lipoprotein lipase (LPL) activation
apoE- uptake of chylomicron remnants and VLDL by liver
Cholesterol sources/synthesis
LDL and HDL.
De novo synthesis of cholesterol occurs in the liver driven by acetyl CoA and ATP
citrate shuttle carries acetyl CoA to cytoplasm. NADPH acts as a reducer.
Synthesis of mevalonic acid in SER is rate limiting step catalyzed by HMG CoA reductase
Regulation of cholesterol synthesis
high cholesterol= inhibit
insulin- promotes cholesterol synthesis
regulation of HMG-CoA reductase
Enzymes involved in transport of cholesterol
LCAT- activated by HDL apoproteins. Adds fatty acid to cholesterol= cholesteryl esters.
HDL can distribute these esters to IDL– becomes LDL, facilitated by CETP (cholesteryl ester transfer protein)
Bioenergetics- thermodynamic considerations for biological systems
open system- biology
cellular/subcellular= closed system
delta U= Q-W
W= zero- deltaV=0
Q mostly considered
delta G= deltaGstandard + RTlnQ
delta G standard- 25 C, 1 atm, standard concentrations of 1 M. However, 1 M of H+ too acidic for body, so use modified delta G with ph 7 as standard 10-7 M H+
(delta G standard)’
ATP as energy carrier
mid level energy carrier- can’t get back lost energy
30 kj/mol
so if rxn requires only 10 kj/mol, 20 kj wasted- can’t get it back. Thats why not too much energy
very negative delta g- neg charges and resonance stabilization for loss of phosphate (-30 kj/mol)
cAMP, creatinine phosphate- even higher energy
G6P, AMP lower energy
Electron carriers name
high energy electon carriers
NADH, NADPH, FADH2, ubiquinone, cytochromes, gluthathione
soluble electron carriers, membrane bound ones
FMN- membrane bound, complex 1 of ETC
proteins with iron sulfer prosethetic group= good electron carriers
Flavoproteins
modified B2= modified riboflavin
nucleid acid derivatives—– FAD/FMN
mitochondria and chloroplasts as electron carriers
other roles:
- modify other B vitamins to be active
- function as coenzymes of oxidation of fatty acids, deccarboxylation of pyruvate, reduction of glutathione
Which steps of glycolysis make ATP
1,3 BPG to 3PG done by 3 phosphoglycerate kinase
PEP to pyruvate by pyruvate kinase (irreversible step also)
Which steps of glycolysis use ATP
PFK-1 : also irreversible and RDS
F6P to F1,6P
glucokinase/hexokinase : also irreversible
glucose to G6P
Metabolism of lactose and sucrose leads to which intermediates of glycolysis
galactose—- glucose 1P to G6P
fructose—– DHAP and glyceraldehyde—– G3P
Which steps of glycolysis make NADH
3GP to 1,3 BPG
glycerol 3 phosphate dehydrogenase
Where does G1P (glucose 1 P) come from?
galactose 1P
G6P to G1P during glycogenesis
G1P to G6P—glycogenolysis
Gluconeogenesis important intermediates
glycerol 3 phosphate (from glycerol of triacylglycerols)
——— converted to DHAP by glycerol 3 dehydrogenase, make NADH
——DHAP can be converted to G3P (glyceraldyhde 3P)
lactate (from fermentation)
—lactate dehydrogenase, lactate to pyruvate, make NADH (Cori Cycle)
glucogenic amino acids (alanine)
————-alanine to pyruvate via alanine aminotransferase
make stuff like pyruvate, oxaloacetate, others
glucogenic vs ketogenic amino acids
and how proteins catabolized
glucogenic– all amino acids besides lysine and leucine
(can be converted to intermediates feeding into gluconeogenesis)- glucose
ketogenic- W, F, Y, I, T, L, K (can be converted to ketone bodies)
proteins unlikely since so important for other shit
deamination/transamination must happen and then carbon skeleton used for energy
amino groups toxic- must be excreted- urea cycle
pyruvate carboxylase
gluconeogenesis, mitochondrial enzyme
converts pyruvate to oxaloacetate, uses ATP and one carbon dioxide to do so
OAA eventually leads to glucose production
activated by acetyl CoA
acetyl CoA inhibits pyruvate dehydrogenase- no more acetyl CoA needed, satiated cell- no more burning glucose, need to make more glucose so activates pyruvate carboxylase
in times of no glucose—- high fats— acetyl CoA made!!!.
acetyl CoA—– pyruvate carboxylase activate— OAA made— eventually leads to gluconeogenesiss
PEPCK — phosphoenolpyruvate carboxykinase
cytoplasm enzyme, gluconeogenesis
oxaloacetate made by pyruvate carboxylase from pyruvate
to enter cytoplasm—–malate aspartate shuttle
OAA to malate—-cytoplasm— malate to OAA
OAA converted by PEPCK to PEP
(requires GTP)
PEP can go all the way back to F1,6BP (rest of rxns reversible)
requires GTP. Induced by glucagon and cortisol to raise glucose levels
PEPCK and pyruvate carboxylase together accomplish the pyruvate to PEP process since that is irreversible
Fructose 1,6 Biphosphatase
converts F1,6 BP to F6P
rate limiting step of gluceoneogenesis
- —oppose PFK (kinase)
- —activated by ATP (high levels so can make glucose, not burn)
- —inhibited by AMP and F2,6BP
F2,6 BP- made by PFK 2- inhibited by glucagon- which promotes gluconeogenesis while insulin stops by increasing F2,6 BP levels
Summary of gluconeogenesis
pyruvate made (alanine dehydrogenase, lactate dehydrogenase)
OAA made
- from pyruvate (pyruvate carboxylase)— high acetyl CoA levels
- glucogenic AA
OAA to PEP (PEPCK)— high glucagon and cortisol levels
F 1,6 BP made
—–reversible reactions from PEP and DHAP (made from glycerol 3 phosphate from triacylglycerol using glycerol 3 phosphate dehydrogenase)
F1,6 BP to F6P—— fructose 1,6 biphosphatase—– rate limiting step of gluconeogenesis
- —oppose PFK (kinase)
- —activated by ATP
- —inhibited by AMP and F2,6 biphosphate
G6P made (from FGP) G6P converted to glucose by glucose 6 phosphatase
Finally have glucose—- gluconeogenesis done in liver. Now, can give glucose to other tissues if blood glucose levels are really low.
Not done as energy source for liver.
Requires lots of energy/ATP- provided by B-oxidation of fatty acids to acetyl CoA (done when low blood sugar)
adipose tissue to liver with fatty acids
during starvation- acetyl CoA- ketone bodies used too
acetyl CoA activates pyruvate carboxylase also
Glucose 6 phosphatase
lumen of ER of liver cells
G6P transported to ER, acted upon by enzyme, and glucose transported to cytoplasm and can leave cell to raise blood sugar
enzyme not used in muscles- can’t convert G6P to glucose to raise blood sugar, only liver can. G6P in muscles—- used only for muscle energy
oppose glucokinase/hexokinase
Ketone bodies
- purpose
- names
during starvation! fasting state
fatty acids to acetyl CoA in liver mitochondrial matrix (B-oxidation)
-excess acetyl CoA converted to ketone bodies via ketogenesis
Ketone bodies= acetoacetate and 3-hydroxybutyrate
Ketone bodies are transported to mitochondrial matrix various tissues- cardiac and skeletal muscle, brain, and renal cortex where they can be metabolized to acetyl CoA and put in citric acid cycle to make energy
—- via ketolysis
brain—- prolonged fasting only. 2/3 of energy from ketone bodies. glucose uptake decreases and so does glycolysis
Ketogenesis
-HMG-CoA synthase converts acetyl CoA to HMG-CoA.
-HMG lyase breaks HMG-CoA to acetoacetate
(byproduct of it is acetone)
-acetoacetate reduced to 3-hydroxybutyrate with NADH
Ketolysis
Thiophorase activates acetoacetate, becomes acetoacetyl CoA to 2 acetyl CoA to be used in citric acid cycle to make ATP
enzyme only present in tissues outside liver so it can’t use its own ketone bodies
Ways to make acetyl CoA Summary
pyruvate dehydrogenase complex
fatty acid (beta) oxidation
ketogenic AA catabolism
ketone body (reverse rxn of making them)]
alcohol
——alcohol dehydrogenase and acetaldehyde dejhydrogenase used to make acetyl CoA from alcohol
—–accompanied by NADH buildup so block citric acid cycle
—–acetyl CoA made by this only used for fatty acid synthesis
Problems with using alcohol to make acetyl CoA
- —–alcohol dehydrogenase and acetaldehyde dejhydrogenase used to make acetyl CoA from alcohol
- —-accompanied by NADH buildup so block citric acid cycle
- —-acetyl CoA made by this only used for fatty acid synthesis
Pyruvate dehydrogenase mechanism
complicated shit, not feeling it bro
look at damn pic and pg 342/341 in kaplan BC
What all is acetyl CoA used for
- citric acid cycle (muscle and adipose)
- fatty acid synthesis
- ketone bodies
- activates pyruvate carboxylase (gluconeogenesis)
- inhibits pyruvate dehydrogenase
- cholesterol synthesis
muscle and adipose- actyl CoA from fatty acids) enters citric acid cycle
liver-
fasting state: acetyl CoA stimulates gluconeogenesis and in fasting state more present than used in citric acid cycle so excess converted to ketone bodies
nonfasting state: fatty acid synthesis
Fatty acid synthesis
- location
- purpose
occurs in liver– then transported to other tissues
excess carbs and protein converted to adipose for storage
stimulated by insulin
end product is palmitate
acetyl-CoA shutting- fatty acid synthesis
major enzyme
acetyl CoA accumulates post meal in mitochondria,
citrate thus accumulates as acetyl CoA+ oxaloacetate combine-slowing of citric acid cycle once satisfied energtically.
citrate diffuses into cytosol and citrate lyase splits into acetyl CoA (cytoplasm) and oxaloacetate (goes back to mitochondria)—–
OAA in cytoplasm to pyruvate can happen- gluconeogenesis (but this happens when starving)- high acetyl CoA levels!
OAA to PEP though needs high glucagon!- won’t happen
acetyl CoA carboxylase
-importance to fatty acid biosynthesis
RDS for fatty acid biosynthesis
enzyme- requires biotin and ATP
activated by insulin and citrate
acetyl CoA + CO2= malonyl CoA
fatty acid synthase/palmitate synthase
multienzyme complex
high insulin levels stimulate
requires B5
NADPH required
NADPH made from pentose phosphate pathway and also from malate to pyruvate!
malonyl CoA , remove CO2= palmitate!
8 acetyl CoA for palmitate (16C)
beta oxidation
location, regulation
mostly in mitochondria, some in perioxisomes
insulin=inhibits
glucagon= stimulates
Beta oxidation process
name enzyme involved/overall job
activation
entry into mitochondria
beta oxidation
activation- fatty acyl CoA synthetase (attach acetyl CoA)
short and medium chains diffuse to enter mitochondria
long chain fatty acids require transport by carnitine shuttle, important enzyme= CPT1
RDS- carnitine palmitoyltransferase 1
beta oxidation- make acetyl CoA and lots of NADH and FADH2- produce ATP via ETC
beta oxidation process
- oxidation of fatty acetyl CoA to form double bond between alpha and beta carbons
- hydration of double bond to form hydroxyl on beta carbon
- oxidation of hydroxyl on beta carbon to form carbonyl
- Splitting of fatty acid into acyl CoA (fatty acyl CoA) + acetyl CoA with addition of CoA-SH
- – beta carbon sticks with acyl CoA and alpha and carbonyl carbons + S-CoA= acetyl CoA
even number fatty acids vs odd number fatty acids
at end:
even #= two acetyl CoA
odd #= one acetyl CoA + one propionyl CoA
proponiyl CoA to methylmalonyl CoA (propionyl CoA carboxylase- biotin)
methylmalonyl CoA to succinyl CoA (methylmalonyl CoA mutase- B12)
succinyl CoA to citric acid cycle/gluconeogenesis also
enoyl CoA isomerase
2,4 dienoyl CoA
B oxidation with unsaturated fatty acid
enoyl CoA Isomerase:
moves double bond to 2,3 position - mononsaturated
2,4 dienoyl CoA:
-converts conjugated double bond to single one so enoyl CoA isomerase can act- polyunsaturated
ETC complex 1
NADH to coenzyme Q (ubiquinone)- 4 protons pumped
NADH + FMN (flavoprotein coenzyme)= NAD+ + FMNH2
FMNH2 + 2iron sulfur cluster= FMN + 2reduced Fe-S
2Fe-S reduced + CoQ (ubiquinone)= 2Fe-S + CoQH2
ETC complex 2
no proton pumping, succinate to coenzyme Q
succinate+ FAD (covalently bound to compelx 2)= fumarate+ FADH2 (succinate dehydrogenase- rxn from citric acid cycle is the enzyme that is complex 2)
FADH2+ Fe-S cluster= FAD+ +Fe-S reduced
Fe-S reduced +CoQ+ 2 H+= Fe-S + CoQH2
ETC Complex 3
cytochrome reductase- other name
coenzyme Q to cytochrome C— Q cycle
4 protons pumped
cytochromes involved- have Fe+2 reoxidized to Fe+3
happens twice for 2 CoQH2 molecules
CoQH2+ 2 cytochrome c (Fe+3)= CoQ + 2 cytochrome c (Fe+2)+ 2H+
ETC Complex 4
cytochrome c to oxygen
2 protons pumped
cytochrome oxidase- becomes oxidized, oxygen reduced to make water
cyanide= inhibitor of cytochrome a and a3 which does this!!!!!
4 cytochrome c (Fe+2) + 4H+ + O2= 4 cytochrome c (Fe+3) + 2H2O
ETC proton motive force
established as protons pumped into intermembrane space
energy from transferring electrons to things with higher and higher reduction potentials- used to pump protons against gradient
NADH shuttle mechanisms purpose
NADH can’t cross into matrix. Electrons from NADH must be transferred to a carrier that can cross membrane–
two mechanisms, each differ in amount of ATP per NADH
Glycerol 3-phosphate shuttle
1.5 ATP, FADH2
glycerol 3 phosphate dehydrogenase
DHAP to glycerol-3P
uses NADH to do so
—-done in cytosol
glycerol 3P to DHAP- another glycerol 3P dehydrogenase on inner mitochondrial membrane that is FAD dependant
FAD to FADH2
then FADH2 to ETC complex 2
1.5 ATP
Malate aspartate shuttle
cytosolic oxaloacetate reduced to malate
malate dehydrogenase— NADH to NAD+
when malate crosses membrane into matrix,
malate dehydrogenase converts malate to oxaloacetate= NAD+ to NADH
NADH in matrix, sent electrons to complex 1—- 2.5 ATP
oxaloactate- transamination to form aspartate
asparate crosses into cytosol—– converted back to oxaloacetate- cytosolic
Chemioosmotic coupling vs conformational coupling
chemioosmotic:
protons flow through F0 ion channel of ATP synthase into matrix
F1 portion of ATP synthase harnesses energy released to do ADP to ATP
conformational:
- indirect relationship between gradient and synthesis
- F1 is like a turbine- harnesses gradient energy, then ADP to ATP done- conformational change
Regulation of oxidative phosphorylation
O2 limited- rate decreases, NADH FADH2 concentration increase= inhibit citric acid cycle
respiratory control
high ADP- allosterically activates isocitrate dehydrogenase—- increase rate of electron transport
Postprandial absorptive state
shortly after eating
anabolism and fuel storage> catabolism
high blood glucose levels- insulin released by Beta cells of pancreatic iselts of Langerhans
insulin secretion directly proportional to plasma glucose
——-enter B cells, increases ATP levels, leads to exocytosis of insulin
Insulin effects:
- glucose uptake in liver and skeletal muscle
- —–doesn’t affect uptake in nervous tissue, RBCs, beta cells of pancreas, intestinal mucosa, kidney tubules
- glycogen synthesis in liver and muscle
- after glycogen done, excess sugar converted to fatty acids by liver- lipid biosynthesis
- VLDL and chylomicron fatty acid deposit via lipoprotein lipase and triacylglycerol synthesis, and supress fatty acid release - adipose tissue
- protein synthesis - muscle tissue
postabsorptive (fasting) state
fasting state
catabolism— need energy
low blood sugar
glucagon, cortisol, epinephrine, norepinephrine, growth hormone, low insulin
fastest response (immediate)
- glycogenolysis in liver to increase blood sugar- glucagon
- release of amino acids from skeletal muscle
- release of fatty acids from adipose tissue (hormone sensitive lipase in liver)—— boxidation
- AA and fats go to liver—- energy for gluconeogenesis (acetyl CoA needed for pyruvate carboxylase, AA for glucogenic!)
later responses (12 hours)
- gluconeogenesis- liver - glucagon
- ——OAA to PEP up (PEPCK) and also F2,6BP decrease so F1,6BP to F6P
- excess acetyl CoA- ketone bodies
glucagon- liver actions (alpha cells—-acts on liver and secreted with low blood sugar )
cortisol-stress–inceased lipolysis and AA degredation and increases blood glucose through gluconeogenesis and enhaces activity of other above
catecholamines- promote glycogenolysis (muscle and liver), lipolysis
prolonged fasting (starvation)
- high glucagon levels and epinephrine
- gluconeogenesis primary source of glucose
- high levels of lipolysis + beta oxidatio
- ketone bodies from excess acetyl CoA
once fatty acids and ketone bodies heavily prevalent in blood, muscles and brain will use
brain shift to ketone (2/3 use)—- reduces need for gluconeogenesis– preserves necessary proteins
thyroid hormones
increase basal metabolic rate
T4- long lasting, slow acting
T3- fast acting, short lived
epinephrine needs them, also help increase rate of intestinal glucose absorption cholesterol clearance
liver- fuel source + role
preferred fuels:
- glucose and excess amino acids (well fed)
- fatty acids (fasting)
role:
- after meal, takes in extra glucose from hepatic portal vein and makes glycogen
- excess glucose= fatty acid synthesis, which are converted to triacylglycerol and released into blood as VLDL
- gluconeogenesis and glycogenolysis during fasting
- forming ketone bodies!
adipose tissue- fuel source and role
preffered fuels
well fed= glucose
fasting= fatty acids/ketones
well fed:
- takes in glucose and triggers fatty acid release rom VLDL and chylomicrons
- ———-lipoprotein lipase induced by insulin
- reesterified fatty acids for storage and glycerol 3P from DHAP from glycolysis with glucose helps make triacylglycerols
- prevents fatty acid release from tissue
fasting
- hormone senstivie lipase- releases fatty acids into circulation
- epinephrine
skeletal resting muscle- fuel source and role
well fed: use glucose + excess AA for energy
–build up protein and glycogen
fasting: use free fatty acids in blood for energy + ketone bodies
skeletal active muscle- fuel source and role
short fast energy- creatinine phosphate
short bursts- anaerobic respiation from stored glycogen
moderate intensity, continous– oxidation of glucose and fatty acids
——if glycogen stores deplete, then fatty acids!
cardiac muscle- fuel source
well fed state+ fasting: prefer fatty acids as fuel and also ketones if present
brain- fuel source
well fed= glucose
between meals- glucose from hepatic glycogenolysis or gluconeogenesis
prolonged fasting= ketone bodies
insulin useless
fatty acids can’t cross blood brain barrier
red blood cells
all states- glucose- anaerobic
insulin useless
BMI
> 30 is obese
mass/height^2
25-30= overweight
Ph
protonated
Ph>pka
deprotonated
