Biochemistry exam 3

3 control strategies for glycolytic pathway

1. allosteric control (fast) 2. phosphorylation (fast, not as fast as allosteric) 3. transcriptional control (slow)

fatty acid synthesis steps

1. condensation (put short pieces to longer chain) 2. reduction 3. dehydration 4. reduction

3 stages of energy extraction from food

1. digestion (no atp synthesis here) 2. breakdown to simple molecules (acetyl group of acetyl CoA) - breakdown of carbs will have ATP investment but net result is more ATP generated 3. Most ATP produced from complete oxidation of acetyl group to CO2 - 4 pairs of electron transfer to electron carriers, proton gradient generated from electron flow to O2, gradient used to synthesize ATP

2 functions of carriers in metabolism

1. enzymes control the flow of free energy and reducing power - NADH and FADH2 react slowly w/ O2 in absence of catalyst - ATP and acetyl CoA are hydrolyzed slowly in absence of catalyst -- both due to high activation energy barrier, these rxns are thermo favorable 2. very few carriers required to donate or accept most activated groups in metabolism - small set of molecules carry out a wide range of tasks

where does glucose come from?

1. gluconeogenesis: glucose synthesis from precursors like pyruvate 2. enzymatic breakdown of glucose polymers (dietary starch and glycogen)

2 stages of glycolytic pathway

1. glucose enter cell passively thru transporters, then it is phosphorylated to glucose-6-phosphate (g6p) then cleaved to two 3C intermediates - needs ATP as phosphate donor (prevents escape back out, help destabilize hexose, makes highly symmetrical product 2. ATP is generated due to the 3C intermediates being further processed, making net gain this is substrate level phosphorylation

3 stages to process fatty acids

1. move TAGs in adipose, convert to fatty acids and glycerol. controlled by catabolic hormones (glucagon (low energy) or epinephrine (signal immediate energy need) 2. at destination tissue, fatty acids joined to CoA (direct entry into CA cycle) then transport to mitochondria for degradation 3. FA broken down to acetyl CoA -> processed in CA cycle

Fatty acid degradation steps

1. oxidation 2. hydration 3. oxidation 4. cleavage

3 enzymes of pyruvate dehydrogenase complex

3 roles: decarboxylation (release CO2), oxidation (transfer one electron pair to NAD+), and transfers acetyl to CoA

what is in the respiratory chain/ electron transport chain

4 protein complexes (1,2,3,4): 3 are proton pumps and 2 is a physical link to CA cycle 3 proton pumps: transport hydrogen across the inner mitochondrial membrane (1,3,4) complex 2 is not a proton pump 2 electron shuttles: Coenzyme Q (Q) and cytochrome C(CytC): pass electron through complex Fe is critical cofactor

which would be expected to positively regulate one or more citric acid cycle enzymes? a. ADP b. glucose c. NADH

ADP glucose is not right b/c it's only found in cytoplasm briefly and needs to be phosphorylated to prevent leakage

when is ATP formed?

ATP is formed from ADP and Pi when fuel molecules (carbs or lipids) are oxidized OR when light is trapped (phototrophs)

Acetyl CoA

Acetyl coenzyme A; the entry compound for the citric acid cycle in cellular respiration, formed from a fragment of pyruvate attached to a coenzyme. when something is called activated, they are linked to CoA

at the start of glycolysis, an enzyme known as hexokinase phosphorylates glucose. at which carbon does the phosphorylation occur? a. C5 b. C2 c. C6 d. C3 e. C1

C. C6 first step of glycolysis, glucose is phosphorylated at the 6-carbon (external to the ring). this happens in the cytoplasm after glucose enters the cell passively through glucose transporters. If the cell didn't 'trap' glucose inside in this way, then it would at times be able to leak back out of the cell through those same transporters down its concentration gradient, once the glucose concentration outside of the cell dropped. Adding the bulky, negatively-charged functional group (i.e. the phosphate) modifies the glucose sufficiently so that it won't be able to fit back out through the glucose transporter.

carbs and fats are catabolized into?

CO2, H20 and useful energy (ATP) ATP can be used for anabolic reactions

cellular respiration

Citrus acid cycle + oxidative phosphorylation respiration: ATP generating process, O2 is ultimate electron acceptor

complex 2 of electron transport chain

Complex 2 is a citric acid cycle enzyme, only entry point for electrons from FADH2 -only one that is not a proton pump, less ATP is formed from FADH2 oxidation compared to NADH oxidation

fatty acid synthase

FA are synthesized by fatty acid synthase. (anabolizing fats, normally not doing this, occurs in specific tissues) goal in FA synthesis: link 2C units together to produce palmitate (16C FA), it's a precursor for other FAs

lipolysis generates what? final products?

Fatty acids and glycerol in liver convert glycerol to pyruvate (3C) or glucose (6C) fatty acid produce ATP after converting to acetyl Coa

The electron transport chain powers the pumping of protons. Where do they go?

From the mitochondrial matrix to the inter-membrane space he majority of the reduced electron carriers (NADH, etc.) produced during catabolism are produced right in the mitochondrial matrix (by pyruvate processing, the citric acid cycle, and fatty acid oxidation); additional reduced carriers from glycolysis can be transported there from the cytoplasm. As these electrons are delivered to Complex I (in the case of NADH) and Complex II (in the case of FADH2) at the beginning of the electron transport chain, electrons favorably move through the transport chain until they reach the final electron acceptor (O2) in Complex IV. The process is so favorable that work can be done during this, and the work is the pumping of protons against their concentration gradient, from the mitochondrial matrix into the inter-membrane space. These protons can then re-enter matrix along their concentration gradient only one way, which is along a rotational path through ATP synthase. As ATP synthase spins, this is sufficient to push Pi onto ADP.

Which of the following need to be done to pyruvate before it is ready to enter the citric acid cycle? ALL of the following except: It needs to be phosphorylated. It needs to have a pair of electrons removed. It needs to have a carbon removed. It needs to get 'activated' by attachment to a carrier molecule.

It needs to be phosphorylated. All pyruvate processing is performed with one amazing enzyme - this multi-step process is oxidative decarboxylation, i.e. (1) harvesting of electrons, and (2) removal of a carboxyl group, which we then breathe out as a molecule of CO2, followed by (3) linkage of the acetyl group onto the CoA carrier. There is an extremely negative deltaGo' associated with then transferring that acetyl group into the citric acid cycle (i.e. onto oxaloacetate). This spectacular enzyme, the pyruvate dehydrogenase complex, is located in the mitochondrial matrix.

catabolism

Metabolic pathways that break down molecules, releasing energy. harvest electrons and send them over to electron transport chain. NEED empty electron carriers so can eventually be full

An extremely important product of the citric acid cycle is:

NADH

difference of NADH and FADH2 oxidation?

NADH is more thermo favorable than FADH2 but both are highly negative electron transport path for NADH is 1 -> Q -> 3-> CytC -> IV electron transport path for FADH2 is 2 -> Q ->3-> CytC-> IV

important product of glycolysis and citric acid cycle?

NADH. the reduced form goes into the electron transport chain

For FA synthesis: NADP+ or NADPH is needed as a carrier? For FA breakdown, NADP+ or NADPH is needed as a carrier?

NADPH is needed for synthesis NADP+ is needed for breakdown. biosynthetic process is reductive from point of view of carbon, electron carrier must be already in reduced form and then become oxidized during reaction. so need reduced form of carrier

what is ultimate electron acceptor in oxidation of carbon? and what is the product of oxidation?

Oxygen is the ultimate electron acceptor, and oxidation product is CO2

What inhibits PDH?

PDH converts pyruvate to AcCoA (this is irreversible). in order to enter CA it needs to be AcCoA PDH inhibited by: high NADH (energy needs have been met) , high acetyl CoA (FA are being degraded already to produce AcCoA +NADH), high ATP

what activates PDH?

PDH converts pyruvate to AcCoA (this is irreversible). in order to enter CA it needs to be AcCoA PDH is activated by reactant pyruvate and high ADP (signal we need energy)

phosphoglycerides

Phospholipids with a glycerol backbone take a phosphatidate (diacylglycerol 3-phosphate) and attach an alcohol to the phosphoric acid (using the C-OH) example is attaching alcohol of serine

Carbon oxidation level

Reduced (most energy) -> Oxidized (least energy) methane, methanol, formaldehyde, formic acid, carbon dioxide

activated intermediates

S-R'. activated malonyl group, attached to CoA. fatty acid degradation is activated because already linked to CoA before degradation.

which is favorable? FA degradation or synthesis?

They are both favorable HOWEVER only when ATP investment in synthesis.

which of these is a polymer of glucose that we can convert back into glucose monomers if needed? a. glycogen b. fructose c. fructose 6 phosphate d. fructose 2,6 biphosphate e. cellulose

a. glycogen glycogen is a polymer of glucose that animals make to store glucose for later use. plants make starch as their glucose storage. can consume glycogen and hydrolyze linkages between the glucose monomers to release free glucose

regulation for glycolysis

activated by low ATP (high AMP or ADP) inhibited by high ATP inhibited by high conc of immediate products inhibited by high conc of downstream products

coenzyme A (CoA)

activated carrier of 2 carbon fragments, coenzyme A is a very large carrier of acetyl groups acetyl CoA hydrolysis is very exergonic

FA synthesis require what

activated intermediate: activated malonyl group (2C unit work w/ neg delta G)

ATP

activated phosphoryl group, carriers of pair of electrons for fuel oxidation

NADH says that electrons _____ delivered to electron transport chain a. are ready to be b. have already been

are ready to be (signals catabolism)

Our figure that compared fatty acid synthesis and degradation shows several molecules ending in -S-R'. What does -S-R' refer to? a. an acetyl group b. CoA c. an enzyme covalently linked to the substrate d. NADH e. a long hydrocarbon

b. CoA This is indicating CoA, and we see its structure in Ch.15. It could be easy to get confused here, because there is an R on the molecule as well, indicating a hydrocarbon (the fatty acid 'tail'). The sulfur is to help distinguish between the sulfur-containing carrier and the fatty acid tail. The CoA is added before fatty acid degradation, and means that the product that is released from fatty acid degradation (acetyl CoA) is ready for direct entry into the citric acid cycle. Similarly, in fatty acid synthesis, the malonyl group already has CoA added. Malonyl CoA is a version of acetyl CoA that has been modified, in an ATP-requiring process, to be ready for fatty acid anabolism.

What feedback could you give if you see a cartoon image of a phospholipid bilayer that shows every head group having a +1 charge? a. Head groups have a net charge of -1. b. Head group charge is variable, and net positive charge is not necessarily the most likely c Head groups have a net charge of zero. d. Head groups have a net charge of +2. e. Head groups have a net charge of -2.

b. Head group charge is variable, and net positive charge is not necessarily the most likely

In the second step of glycolysis, the cyclized form of glucose (now phosphorylated) is converted to a cyclized form of fructose. What is the purpose? a. The fructose has fewer carbons. b. The fructose is more symmetrical. c. The fructose has more carbons. d. The fructose has more oxygens. e. The fructose has fewer oxygens.

b. fructose is more symmetrical The major objective in glycolysis is to break one 6-carbon glucose into two 3-carbon pyruvate molecules. Part of the strategy that is employed is to, early on, make the molecule as symmetrical as possible. Cyclized glucose has only one carbon external to the ring; by contrast there are several possible forms of cyclized fructose (as shown in Ch.11), including a form that has four carbons internal to the ring and both the 1-C and the 6-C external to the ring. That last form is superior to glucose in terms of symmetry and potential for being split into nearly identical 3-C units (which through a bit of processing will indeed become identical 3-C pyruvates).

Which one of the following is a signal that acetyl CoA carboxylase should perhaps be active? a. high palmitoyl CoA b. high ATP c. high glucagon d. high AMP e. high epinephrine

b. high ATP Carboxylases effectively add a carboxyl group onto molecules; look closely at the difference between acetyl CoA and malonyl CoA to see that this is the result of acetyl CoA carboxylase performing its work on acetyl CoA during the process of acetyl CoA 'activation'. This enzyme is considered critical in fatty acid metabolism - its regulation is essential to how we decide whether or not to anabolize fats. Metabolic pathways are complicated, but in with respect to fats, when ATP is plentiful, then we have no need to break down any more carbon skeletons, and can favor anabolism. (Whether that will be in the form of fats or carbohydrates is a more complicated matter.) All of the other signals indicated here are consistent with turning off acetyl CoA carboxylase, because ATP stores are depleted, fat stores are high, and/or the body has detected that a 'fight or flight' response may require unusually high resource consumption in the near future.

PfKase is a kinase that is also negatively allosterically regulated by ATP. thinking about PFKase's two ATP binding sites, which can be true? a. allosteric negative regulatory site has higher affinity for ATP b. substrate binding site has higher affinity for ATP c. both must have equal binding affinity for ATP

b. substrate binding site has higher affinity for ATP because priority is to use ATP for the process of glyolytic pathway. so if there's 1 ATP left it's better to have a high affinity for ATP

glycolysis

breakdown of glucose (6C) to 2 pyruvate (3C) producing small amount of ATP (2) and NADH (2) - ATP investment before ATP production - NADH is produced (reduced form)

cholesterol

built from 4 hydrocarbon rings (3 hexagon, 1 pentagon and hydrocarbon tail) stays in membrane (gets stuck, very hydrophobic), in animal absent in prokaryotes the OH interacts with phospholipid head, hydrocarbon interact with phospholipid HC tails

Our textbook figure does not show how permeable a gas like O2 is across a phospholipid bilayer. Which one of the following best summarizes its likely permeability? a. Better than Cl-, but worse than a steroid hormone. b. Better than glucose, but worse than glycerol. c. Better than anything that we saw in our figure. d. Better than Na+, but worse than glucose. e. Better than tryptophan, but worse than indole.

c. Better than anything that we saw in our figure. Gas molecules are in very rapid motion, and are able to ease their way between the phospholipid molecules readily. Molecules that are fairly hydrophobic can diffuse across the phospholipid bilayer if needed, while polar and charged substances require the assistance of membrane-embedded proteins (channels, pumps, etc.). Gases do not require any assistance to move across the membrane. Be sure to review the other options, consulting the figure, to see why they are incorrect. Keep in mind that steroid hormones (unlike cholesterol) are just hydrophilic enough to pass through the membrane and out the other side because they lack the hydrophobic tail and instead tend to have one additional polar functional group.

Which one of the following is most thermodynamically favorable? a. Using an inorganic phosphate from water to phosphorylate ADP. b. Complete oxidation of three glucose molecules. c. Complete oxidation of one 18-carbon fully saturated fatty acid. d. Linkage of two acetyl CoA molecules to each other to extend the acyl chain length to four carbons. e. Linkage of one oxaloacetate molecule to one acetate molecule.

c. Complete oxidation of one 18-carbon fully saturated fatty acid. Fats (lipids) are such an incredible store of energy for two reasons: they are hydrophobic and so are stored with very little water, and also because they are an exceptionally reduced form of carbon. As a result, there is a lot to be done in order to convert each carbon (oxidize it) to carbon dioxide. Carbohydrates, by contrast, are a moderately reduced form of carbon, and therefore there is less to be done to convert each carbon to carbon dioxide. More electron pairs are harvested during the oxidation of each carbon in a lipid, and therefore more electron pairs are delivered to the electron transport chain, and therefore more ADP molecules are rephosphorylated when lipids are oxidized.

FA synthesis is highest when

carbs and energy are plentiful and FA is scarce

rate of glucose to pyruvate conversion is regulated to meet what 2 needs

catabolism: break down glucose to generate ATP anabolism: provide building blocks for synthesis reactions

what happens in the mitochondrial matrix?

citric acid cycle, pyruvate processing, fatty acid oxidation

first step in glycolysis does what: produces NADH, consumes NADH, produces ATP, consumes ATP

consumes ATP

oxidative phosphorylation

convert electron transfer potential of NADH or FADH2 into ATP highly exergonic sets up proton gradient that can be used to power highly endergonic ATP synthesis. coupling thermodynamically favorable and unfavorable reaction electrochemical potential of ion gradients across membranes powers most of cellular ATP synthesis

At a certain step in either fatty acid synthesis or degradation a carbon-carbon single bond is converted to a carbon-carbon double bond. This is a redox reaction. When the carbon skeleton gains a double-bond, this is a/an ________ reaction, indicating that a a/an ________ reaction is taking place. a. oxidation; anabolic b. reduction; catabolic c. reduction; anabolic d. oxidation; catabolic

d. oxidation; catabolic

PFKase catalyzes which step in glyolysis?

does NOT catalyze the first step catalyzes the first committed glycolytic step

why does ATP have a high phosphoryl potential?

due to it's structure. differences between ATP and it's reactants. ATP has high tendency to transfer phosphoryl group to water. 1. resonance stabilization: Pi has greater resonance stabilization than ATP 2. electrostatic repulsion: ph7 ATP has 4 negative charges which are near each other, this repels each other which can be relieved by ATP hydrolysis 3. stablization due to hydration: water molecules have stabilization effect, more water molecules can bind the negatively charged ADP+ Pi than ATP

what is driving force of oxidative phosphorylation?

electron transfer potential of NADH/ FADH2 relative to O2 significant energy released by reducing O2

pfkase

enzyme catalyzing irreversible reaction in glycolysis. converts fructose 6 phosphate to fructose 1 6 biphosphate. it adds a phosphate makes the fructose super symmetrical, making it easier to cleave afterwards into 2 equal 3 carbon products

ATP hydrolysis is exergonic or endergonic?

exergonic

carbs or fats have more reduced carbon?

fats have more reduced carbon, they are a more efficient fuel source look at glucose figure vs. fatty acid figure. more C-O = more oxidized More C-H = more reduced

triacylglycerol (TAGs)

fatty acids that are being stored, FA are oxidized from TAG for energy note the ester linkage, glycerol backbone

In the absence of an enzyme, hydrolysis of ATP is thermodynamically _______ and kinetically _______.

favorable; unfavorable

for fatty acid breakdown, we need the blank form of an electron carrier as a reactant

for fatty acid (highly reduced) breakdown we need the oxidized form of the electron carrier as a reactant

citric acid cycle

fuel enters as acetyl CoA (acetyl group is fully oxidized to CO2) during oxidation, electron is lost and passed to NAD+ and FAD then the electrons are used in oxidative phosphorylation (O2 reduced to H20 and proton gradient established) 2C acetyl enters, 2C exit (CO2) and 4C acceptor is regenerated before new acetyl is transferred in

what happens in the mitochondrial cytoplasm

glycolysis, fatty acid synthesis

inhibit acetyl CoA carboxylase (inhibited by conditions that signal energy need or FA abundance)

high AMP (low ATP), high palmitoyl CoA (signal FA abundance), catabolic hormones like glucagon (low energy) and epinephrine (immediate energy need).stimulate release of FAs from TAGs

activate acetyl CoA carboxylase signals: (activated by conditions that signal energy abundance)

high ATP, high cirtrate (1st intermediate in CA cycle, signal raw materials and energy for FA synthesis), high insulin

since glycolysis is inherently favorable, the reverse process of gluconeogenesis (creating glucose from pyruvates) is *not* favorable and would require the use of 'activated' intermediates that were created through the use of ATP. Another prediction is that a signal that would favor gluconeogenesis is: high ADP high citrate high fructose 2,6-bisphosphate low acetyl CoA

high citrate

why are TAGS highly concentrated stores of metabolic energy?

highly reduced and anhydrous (like associated w/ like)

what regulated acetyl CoA carboxylase?

hormones, ATP, citrate, insulin, catabolic hormone (glucagon)

phospholipid chemical structure

hydrophillic head, hydrophobic tail has a phosphate, glycerol, and fatty acid

what is permeable and impermeable to lipid bilayers?

impermeable to ions and most polar molecules size of # of atoms doesn't predict permeability. ex. trp is huge and can cross membrane compared to Na+, cholesterol is huge and can also cross gases pass through easily, it's permeable to gases

oxidation of carbon fuels

important source of cellular energy. carbon in fuel molecules (glucose or fats) is oxidized into CO2 => the electrons captured are used to make ATP from ADP and Pi The more reduced a carbon is, the more free energy is released ( so oxidation of lipids > carbs)

Trp is a bulky hydrophobic amino acid and has an indole-containing side chain so ______ blank___ passes through lipid bilayer more readily. Indole or Trp?

indole is very hydrophobic, Trp is more polar, has alpha amino and carboxyl indole will pass the bilayer more readily

Phosphatidate (diacylglycerol 3-phosphate)

key intermediate to make phosphoglycerides carboxyl group of 2 fatty acids (green), glycerol backbone (black), phosphoric acid (pink)

acetyl CoA carboxylase

key regulator of FA synthesis and degradation. catalyses committed step in FA synthesis (production of activated 2C malonyl CoA), ATP is required to make malonyl CoA

pyruvate dehydrogenase (PDH)

links glycolysis and citric acid cycle in aerobic condition: pyruvate transported actively (use ATP) into mitochondrial matrix, then oxidatively decarboxylated by PDH to form AcCoA in anaerobic condition: pyruvate converted to lactate or ethanol, doesn't allow entry into CA or oxidative phosphorylation but does regenerate NAD+

which is more reduced? lipids or carbohydrates?

lipids are more reduced than carbohydrates

which is more reduced form of carbon? carbohydrates or lipids?

lipids. pasta more oxidized than butter.

fatty acids

long hydrocarbon chains with different lengths an different degrees of cis unsaturation (cis is double bond), ending w/ carboxyl groups

acetyl coA carboxylase should be inhibited by: high atp or low atp

low ATP

steroid hormones (estrogen, testosterone)

made from cholesterol but LACK hydrocarbon tail and has a polar group nonpolar enough to leave and diffuse through blood, polar enough to leave interior of membrane membrane lipid, also very nonpolar

control of citric acid cycle

negative regulator: ATP, NADH, immediate products positive regulator: ADP and NAD+

fatty acid characteristics: how many carbon, branch or unbranch, charged?

normally even number of carbons, always add 2 carbons from activated acyl group normally unbranched, charged at physiological pH (carboxyl group pka 3-4)

when does citric acid cycle begin?

occurs after conversion of pyruvate to acetyl CoA

permeability of outer vs inner mitochondrial membrane

outer: quite permeable to small molecules and ions b/c of high level of porin expression inner: impermeable to ions/ polar molecules, transporters needed for pyruvate, citrate, atp

Fatty acid degradation

oxidative reaction, convert FA to activated acetyl unit (ex. acetyl coA) because acetyl group alone can't enter CA cycle. activated FA is oxidized and introduces a double bond, double bond is hydrated introduce OH group, alcohol oxidized to ketone, FA is cleaved to yield acetyl CoA and FA chain. FA has even # of C's it's saturated until converted into acetyl CoA units

sphingomyelin

phospholipid with no glycerol backbone, has a sphingosine backbone. it's an amino alcohol, the fatty acid is attached by amide bond the blue is sphingosine

what is the reduced form of NAD/NADH, FAD/ FADH2

reduced form: NADH and FADH2 reduced= carry electrons

reduction of blank, the final electron acceptor, is highly blank a. NAD+/NADH; exergonic or endergonic b. H20; exergonic or endergonic c. O2; endergonic or exergonic

reduction of O2, the final electron acceptor, is highly exergonic

if you have an organelle that is designed to contain lipid, the membrane would be:

single layer of membrane lipids, tail on inside (near lipid), head on outside (near cytoplasm) like attracts like (polar head + polar water) (lipid + tail)

what happens when phospholipid + water?

spontaneous and rapid,form lipid bilayers. self-assembly due to hydrophobic interaction, vderw attractive forces between hydrocarbon tails, electrostatic and H bonding attraction

glycolipid

sugar containing lipids, no phosphate, sugar facing extracellular side of membrane, backbone will either be sphingosine or glycerol image is an example of a glycolipid, cerebroside

What does S-R' stand for?

sulfur-containing (-S-R') indicates a large carrier molecule which is CoA in the breakdown reaction

which is more favorable thermodynamically? a. hydrolyzing ATP b. transfer pair of electron from NADH to oxygen

transfer pair of electron from NADH to oxygen. this is oxidative phosphorylation

what turns glycolysis on and off? what turns gluconeogenesis on or off?

turn off glycolysis: high ATP turn on glycolysis: high F2, 6BP Turn off gluconeogenesis: high F2, 6BP turn on gluconeogenesis: high ATP

unsaturated vs saturated fatty acids

unsaturated: has double bonds, it is always cis NEVER trans saturated: no double bonds (if fully)

anabolism requires ATP investment? T/F

yes. anabolism requires ATP investment, build fuel molecule

which has a higher yield from completed oxidation? carbohydrates, fats or proteins?

yield from complete oxidation of FAs is more than 2x of carbs and proteins. because glycogen is more oxidized than fats.