Metabolism II Flashcards
GLYCOGEN PATHWAYS
- Glycogen is a polysaccharide that is the main form of glucose storage
- Consists of a chain of glucose monomers connected by alpha-1,4-glycosidic linkages
- Also includes branches via alpha-1,6-glycosidic linkages (formed by different pathway)
- Glycogenolysis = breakdown of glycogen into glucose monomers
- Glycogenesis = glycogen synthesis = addition of glucose monomers to form polymer
Glycogenolysis 2
- Glycogenolysis = breakdown of glycogen into glucose monomers
- Glycogen is broken down into glucose-1-phosphate by glycogen phosphorylase
- Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase
- Glucose-6-phosphate can then enter glycolysis
Glycogenesis 2
= glycogen synthesis = addition of glucose monomers to form polymer
• Glucose converted to glucose-6-phosphate
- G6P converted to glucose-1-phosphate by phosphoglucomutase
- G1P converted to UDP-glucose by uridyl transferase
- UDP-glucose is added to glycogen polymer by glycogen synthase
- Glucose addition requires a primer in the form of glycogen or glycogenin protein
- Storage of glucose as glycogen reduces solute load in cells
- Less water is required to solvate glycogen than millions of glucose molecules
- Storage as glycogen prevents spontaneous degradation of glucose
Hormonal regulation of glycogen pathways
1.
- For blood-sugar homeostasis:
- Glucagon promotes glycogen breakdown
- Insulin promotes glycogen synthesis
Hormonal regulation of glycogen pathways
- fight or flight
For fight-or-flight:
- Epinephrine stimulates glycogen breakdown
Gluconeogenesis
- De novo synthesis of glucose
- Occurs mostly in liver
- Raises blood glucose levels
- Works in tandem with glycogen breakdown
- Can use pyruvate, lactate, glycerol, some amino acids as carbon sources
USED TO RAISE BLOOD SUGAR***
Not all cells do this, happens mostly in the liver. Happens at the same time probably as break down of glycogen* when haven’t eaten in a while, definitely breaking down glycogen, our next move would be to do gluconeogenesis
Gluconeogenesis Steps
Many steps are same as in glycolysis but reverse direction=
Three steps are not simply the reverse of glycolysis:
Pyruvate → PEP
Fructose 1,6 – bisphosphate → fructose 6-phosphate
Glucose 6-phosphate → glucose
Pentose Phosphate Pathway
Alternative pathway for glucose metabolism
G6P is not broken down to produce ATP
Pathway is primarily anabolic, not catabolic
Occurs in cytoplasm, especially in liver and adrenal cortex
Pentose Phosphate Pathway 2
Cells do this pathway for two main reasons:
- To generate NADPH
- NADPH differs from NADH by one phosphate group
- NADPH acts as a reducing agent
- NADPH needed as cofactor in synthesis of nucleic acids and fatty acids
- To synthesis phase to produce five-carbon (pentose) sugars
* Ribose and deoxyribose used for synthesis of nucleic acids
Protein Metabolism
Proteins can hydrolyzed into amino acids and then deaminated
Deamination = amino group removal
Deaminated amino acids can feed into glycolysis as pyruvate
Deaminated amino acids can feed acetyl CoA formation
Deaminated amino acids can feed into TCA as α-ketoglutarate or oxaloacetate
Amino groups from amino acids are incorporated into urea for excretion
Lipids
Lipids = a non-polymer class of macromolecule
Examples include fatty acids, mono-, di-, and triacylglyerols (triglycerides)
Triglycerides can be metabolized into glycerol and fatty acids
Glycerol enters glycolysis
β-oxidation breaks fatty acids into 2C pieces, then converted to acetyl CoA → TCA
Other examples of lipids: sterols and sterol esters (e.g., cholesterol); waxes; tocopherols (Vitamin E)
Fatty acid catabolism
Fatty acids are prepared for beta-oxidation in the mitochondrial matrix
In order to enter the matrix, most fatty acids require the carnitine shuttle
Carnitine shuttle
The carnitine shuttle consists of three steps:
- A fatty acid (acyl-CoA) is transferred to carnitine on outer mitochondrial membrane
- The acylcarnitine is shuttled into the matrix
- The acylcarnitine is re-converted to the fatty acid (acyl-CoA) on inner membrane
Beta-oxidation 1
Beta-oxidation = breakdown of fatty acids
- we get fats in our diet in lots of different forms, break big chunks of fat into smaller chunks of fat, chemically process them in digestion chapter
- we break down our lipids get fatty acids, triglyceride single glyercol 3 fatty acids chains, so we have these fatty acids and what we want to do is break them down and this process beta oxidation is how we harvest energy from fatty acids just like the whole pathway glycolysis and krebs, how we harvest energy from sugars* so beta oxidation takes place in mitochondira matrix, first issue of getting molecules into the mitochondrial matrix*
** beta odication puts carbonyl group on beta carbon, that is the same thing as 3-hydroxyacly-CoA, so beta-hydroxy aclycoa and 3-hydroxylacl-coa are the same thign!
Beta-oxidation 2
Beta-oxidation of saturated, even-chain fatty acids (as acyl-CoA’s) proceeds in 4 steps:
- Dehydrogenation by acyl-CoA dehydrogenase
- Yield: 1 FADH2
- Different isoforms of enzyme have different affinities for fatty acids of different lengths
- Hydration by enoyl-coA hydratase
- Dehydrogenation by beta-hydroxyacyl-CoA dehydrogenase
• Yield: 1 NADH
- Cleavage by acyl-CoA acetyltransferase (also called 3-ketoacyl-CoA thiolase)
- Yield: 1 acetyl-CoA and a fatty acid that is shorter by two carbons
- Acetyl-CoA can then enter the Krebs cycle
Odd Chain fatty acids
Odd-chain fatty acids are broken down to acetyl-CoA molecules and propionyl-CoA
- Propionyl-CoA is metabolized to succinyl-CoA
- Succinyl-CoA then directly enters the Krebs cycle
- Odd-chain fatty acids are rare in nature
- (if given choice of odd versus even, then you want odd!)
Ketone Bodies
An alternate energy source
Can be especially important for the brain
Produced under conditions of low caloric intake or carbohydrate restriction
Produced in the liver, in the mitochondria
Produced from acetyl coA
Excess acetyl coA cannot be used directly in Krebs because there’s not enough oxaloacetate to react with it
High levels of circulating ketone bodies make blood more acidic
Ketone bodies enter the Krebs cycle as acetyl-CoA
Where are ketone bodies produced?
Produced in the liver, in the mitochondria
Produced from acetyl coA
Excess acetyl coA cannot be used directly in Krebs because there’s not enough oxaloacetate to react with it
ketone bodies are used directly by the brain. if really really in a pinch brain has a way to use ketone bodies, prefers glucose but it can use ketone bodies plan B. CANNOT use fatty acids*** so have to have fatty acids broken down into acetyl-coa, aceyl-co gets turned into ketone bodies and that in turns supplies hte brain
Why does the body turn acetyl-CoA into ketone bodies when glucose-starved?
Acetyl CoA can’t be circulated for two reasons: it’s a high energy compound and it’s labile. So it’s not a stable form for circulation to tissues. Also acetyl coA cannot cross cell membrane.
Ketone bodies are an alternate fuel source. More importantly, they are water soluble analogs of fatty acids. This is important since, during starvation there is fat breakdown and excess fatty acids circulate in blood. However, fatty acids cannot be used by brain as fuel since, they cannot cross the blood brain barrier. Liver by producing ketone bodies helps brain cells during starvation.
Also, these ketone bodies, as such, can be used by other tissues as well. There by other tissues refrain from using glucose. Hence, ketone bodies have a glucose-sparing effect. This glucose will be available for tissues like brain and red cells for use.
ketoacidosis
Extreme form → ketoacidosis (also called ketosis)
Seen in uncontrolled diabetes
Identifiable as the smell of acetone on the breath
three kinds of ketones bodies are:
acetoacetate, beta-hydroxybutyrate, and acetone
= made from acetyl coa, issue say someone eats a very high fat diet, ton of acetyl coa waiting to get into krebs cycle, but not a lot of acetyl coa can enter krebs cycle immediately, each acetyl coa needs an oxoloactate! So oxoloactate is limiting, so only so much acetyl coa waiting in line to enter krebs cycle, huge traffic jam and then coenzyme A, big molecule not good to have a lot of that soaked up acetyl coa sitting there twiddling thumbs to get into krebs cycle, so from that body makes ketone bodies instead*
acetone
acetoacetate
beta-hydroxybutyrate
Fatty acid biosynthesis
Fatty acid biosynthesis is a non-template phenomenon
Carbohydrate synthesis is also non-template
By contrast, RNA and DNA synthesis and protein translation depend on templates
Non-template synthesis depends on several variables:
- Expression levels of relevant enzymes
- Availability of substrates
- Localization of enzymes
Biosynthetic pathways 1
Straight-chain fats can be built up using acetyl-CoA as a precursor
Process occurs in the cytosol
Acetyl-CoA can come from pyruvate
Acetyl-CoA is converted to malonyl-CoA
Enzyme is acetyl-CoA carboxylase
Reaction requires ATP and CO2
Malonyl-CoA is spontaneously decarboxylated
This drives condensation with the elongating fatty acid chain
Biosynthetic pathways 2
Condensation reactions are catalyzed by fatty acid synthase (multi-enzyme complex)- reaction in which a water is removed, very general term but if put together 2 amino acids and make a peptide bond you are kicking out water molecule* in some bio classes people refer to it as dehydration synhtease, a lot of examples make a polymer, put two things togehter and kicking out a water* JUST TAKING OUT A WATER MOLECULE* goes with building things up, can build up an individual fatty acid as well*
Elongation results in the 16-carbon FA, palmitate
Pathway uses NADPH, converting it to NADP+
NADPH is mainly produced by pentose phosphate pathway
Further elongation can be achieved by enzymes on the smooth ER
Synthesis of lipids that are essential in structural and signaling roles in the cells and tissues may be accomplished through pathways involving phosphatidic acid
it requires NADPH becuase enzyme is requiring NADPH* so particular nezyme that does this job evolved to require NADPH as opposed to some other energy source*
Within a eukaryotic cell, the β-oxidation of fatty acids takes place in:
A.the cytosol.
B.the rough endoplasmic reticulum.
C.the mitochondria.
D.the ribosomes.
C.
the mitochondria.
β-oxidation is the process by which fatty acids are broken down two carbons at a time to produce acetyl-CoA. This process is carried out within the mitochondria.
The first step of fatty acid synthesis is depicted below. In this process, an activated acetyl-CoA molecule reacts with a unit of malonyl-CoA to form an intermediate product.
Which sequence of reaction types, if catalyzed by appropriate enzymes, could convert this intermediate into the corresponding fatty acid product?
A.Reduction → reduction → hydration
B.Reduction → dehydration → oxidation
C.Reduction → dehydration → reduction
D.Reduction → hydration → double dehydration
C.
Reduction → dehydration → reduction
This intermediate must first be reduced at the carbonyl farthest from the CoA substituent, producing a hydroxyl group. The resulting species will then be dehydrated, forming a double bond, which will finally be reduced in the last step. This is the exact opposite of the process by which fatty acids are oxidized.
In which of the following locations can ketolysis NOT occur?
A.
The brain
B.
The liver
C.
Skeletal muscle
D.
Cardiac muscle
A.
The brain
Ketolysis can occur in the brain in situations of low blood glucose.
B.
The liver
Ketolysis, or the breakdown of ketone bodies, is a metabolic process that can provide energy. The liver lacks a particular enzyme required for this process.
C.
Skeletal muscle
Ketolysis can occur in skeletal muscle in situations of high activity and/or low blood glucose.
D.
Cardiac muscle
Ketolysis can occur in cardiac muscle in situations of ischemia and/or low blood glucose.
In gluconeogenesis….. fact about PEP=
for PEP Alanine can be converted to pyruvate in the liver, then fed directly into the pathway.
Which phase of the pentose phosphate pathway would be most affected if this enzyme were to become nonfunctional?
A.
Oxidative
B.
Initiation
C.
Non-oxidative
D.
Termination
The protein structure for transketolase is shown below, along with the molecular structure of its cofactor, thiamine pyrophosphate……
Question 14- QBank 11-25
Which of the following is FALSE about ATP and its hydrolysis?
A.
The ΔG for ATP hydrolysis is nearly equal to the ΔG for ADP hydrolysis.
B.
Two rounds of ATP hydrolysis yield AMP.
C.
The ΔG for ATP hydrolysis is pH-dependent.
D.
ATP contains two high-energy phosphate bonds.
A.
The ΔG for ATP hydrolysis is nearly equal to the ΔG for ADP hydrolysis.
Both phosphate bonds are very high energy bonds, and release a similar amount of energy when broken.
B.
Two rounds of ATP hydrolysis yield AMP- Two rounds of hydrolysis, with each round removing one phosphate group, would result in AMP, with one remaining phosphate group attached.
C.
The ΔG for ATP hydrolysis is pH-dependent- CORRECT
∆G is not affected by pH. The remaining choices are accurate – one high-energy bond can be hydrolyzed to yield ADP, and the second can be hydrolyzed to form AMP. Interestingly, the ∆G value for ATP hydrolysis is almost identical to that for ADP hydrolysis, with both reactions being highly exergonic (negative ∆G).
D.
ATP contains two high-energy phosphate bonds.
A high-energy phosphate bond is formed when one phosphate binds to another phosphate group. There are two such bonds in the structure of ATP, with the innermost phosphate bound to a carbon atom on the sugar.
Carnitine shuttle 2
Beta- oxidation 3 (how the mechanisms work)
- The top molecule on fatty acid beta oxidation page- not technically a carboxylic acid, hydrocarbon chain going on left side of molecule, S-CoA, technically a fatty acyl coA, that is the starting material for break down, so if have an actual fatty acid from something you have eaten have to turn it into a fatty acyl coa* then have to use this big complex of proteins and all kinds of fancy footwork to get the fatty acyl coa into the mitochdornia matrix, so transport issues!
- The name to know for that don’t think have to know all the details, but the process is called the Carnitine shuttle* and any enzyme you come across that is a carinitine acyl transferases or anything with transferases in it in this context means it is involved in bringing fatty acyl coa into mitonchondria matrix so it can be very chopped up for energy*
Beta- oxidation 4 (how mechanism works cnt.)
So once inside cell in mitochondira matrix, probably in much bigger form something we ATE went to blood stream, digeative tract mitochondria of cell… so now ready for real metabolic pathway to take plce, all the other stuff just alluded to quickly will fill in when talk about digestion* how do these moelcuels get ot cells from stuff that we eat, how does it go from mouth all the way to cell of body, form is changing but what we wnt to talk about now metabolism part of it
- what happens when have fatty acyl-coa in mitochondria*
1. so the first reaction, involves creating a double bond between the alpha and the beta carbons, so to review that nomenclature, C=0 has c to its left, one away, so that is refered to as alpha carbon, one more over is the beta carbon–>FAD gets reduced to FADH2 no surprise that involves a dehydrogenase* - As FAD is reduced something else needs to be oxidized* that represents an oxidation* with carbon skeleton, FADH2 is reduced*
3. Add water across double bond, OH on beta carbon, then another oxidation of C skeleton, OH turns into ketone group, and while the carbon skeleton is oxidized, NAD+ is reduced to NADH, and that is the other dehydrogenase step*
Beta-oxidation 5 (how it works cnt.)
- Then we have a substution reaction that happens ; yellow arrows, CoASH, nuc lone pair on sulfur, it is attacking the carbon, electrons go up then go down and the structure boxed in orange is the leaving group!
That is acetyl coa!
Net result of these 4 steps is to split off an acetyl coa from the fatty acid chain* not an accident that most fatty acids in our bodies have an even number of carbons, because we build them up and break them down two carbons at a time, typical scenario that maybe the molecule at the top of this page had a total of 14 carbons or 16 or 18 carbons, and then after we go through all the steps all the way down this page, split off an acetyl coa have a leftover molecule that has 12 carbons. Then we go back around to the top and the 12 carbon moelcule goes through this algorithm we split off another acetyl coa, then we have a 10 carbon remained fatty acyl coa and then we do it again and again, until we have broken down our fatty acid unit, a whole bunch of aceyl coa
Beta- oxidation 6 (how it works cnt.)
So you get really a lot of fadh2 and nadh frm this process
Imagine 14 carbon fatty acyl coa =7 nadhs make 7 rounds, if 14 chopping up to 14 c units gives us 7 acetyl coa molecules, 6 rounds* of beta oxidation will always be one fewer cut mark, each red cut mark represents a round fo beta oxidation! Everytime we go thrugh a round fo beta oxidation, get an fadh2 and an nadh, in this process get 6 nadhs and 6 fadh2*
ON TOP OF everything we get from acetyl coas, also made 7 acetyl coas, and each one of those acetyl coas in theory may be able to enter the krebs cycle!
Overall very high yield per gram of fatty acid you can make more atp then you can per gram of glucose**- every round of beta oxidation get nadh and fadh2 adds, take that and go into krebs so technically making a LOT MORE- fat stores are our ultimate energy reserves, glucose fat is our real energy store* it is a very efficient way to store energy voer longer periods of time*
overall very high yield per gram of fatty acid can make you more atp then you can per gram of glucose know that fact
Acetyl coa can enter krebs cycle, CANNOT ENTER GLUCONEOGENESIS can’t take fatty acids break down to aceyl coa then go backwards to pryvuate then pryuvate ot go up through gluconeogenesis to glcusoe, that doesn’t happen in mammals, very important because it means that we can’t get glucose from fats*
Lipid synthesis
If think about fatty acids being built up, they are built up two carbons at a time by an enzyme called fatty acid synthase, malonyl coA two carbons of malonyl coA that get loaded onto fatty acid chain, keep cycling around with fatty acid synthase adding two more carbons, two more carbons, want to make a 14 c fatty acid
Really really important to understand two carbons being added on are not coming from acetyl coa coming from slightly bigger molecule called malonyl CoA, meaningful when two carbons added onto growing fatty acid chain, carboxyl group on left gets driven off as Co2 that process of releasing co2 provides enormous forward drive for this reaction
Entropy point of view producing a gas and driving it off, why adaptive for malonyl coa to be source of these two carbons rather than acetyl coa, this whole process requires nadph* so remember nadph can be generated through PPP and then you need it for lipid synthease, this is where it is needed for this reaction*
Odd Chain fatty acid synthesis 2
Not really relevant so much in real life context thought experiment that comes up a lot in biochem classes, the question is that if you are only to eat fats all fat diet it is better to have some odd chain fatty acids then even if only eating fats
In beta oxidation process chopping up fatty acids splitting up two carbons and two carbons, 15 c total get down to end 3 carbon molecule left, instead of last acetyl coa so the 3 carbon molecule you have left is called propinyl coA
Propinyl coA through a whole other pathway you don’t need to know about can be converted to succinyl coa intermediate in krebs cycle that can be turned into oxolacate, so that means can supply one more oxolaoacateate so can take one more acetyl coa into krebs cycle so making one fewer ketone body!
- Consider a pyruvate molecule during aerobic respiration. After this molecule enters the mitochondrial matrix, its full metabolism will generate how many ATP?
15
means after all is said and done will generate 15 atp after ETC
- one significant feature of fermentation in human muscle cells is that it:
a. releases Co2
b. regenreates NAD+
c. yields alcohol as an end product
d. produces ATP by oxidative phosphorlyation
b. regenerates NAD+****
does not release CO2 because bacteria and humans do not release co2 through fermentation** unlike with others like yeast*
ethanol end product in yeast
under aerobic conditions when there isnt enough oxygen present we do glycolysis* we cannot do more than that, so under anaerobic conditions get all atp from glycolysis* pretty low yield than if had O and id whole aerobics conditions to the end with oxidative phosphorylation, but couldn’t keep doing lgylocisys unless had some way of regernatign NAD**** with fermentation* All fermentation runs produce NAD+ as a product, that is important b/c glycolysis uses NAD+ and turns it into NADH, under aerobic conditions NADH is oxidized in complex I*
GLYCOLYSIS= NAD+ is converted to NADH***
Under aerobic conditions: NADH—> NAD+ at complex I of the ETC* under anaerobic conditions NADH goes back to NAD+ through fermentation** but the point iS YOU NEED NAD+ FOR GLYCOLYSIS**** if no way to regenerate NADH do not get ATP from glycolsis anymore*
only version that occurs in yeast that releases CO2
- A proton-uncoupler like dinitrophenol does which of the following?
a. Prevents the oxidation of NADH at the bginning of the electron transport chain
b. inhibits the release of heat from the electron transport chain
c. makes the intermembrane space more acidic
d. Reduces the amount of ATP produced per glucose
d. Reduces the amount of ATP produced per glucose*
REMEMBER a proton uncoupler pokes holes in membrane, creating channels that H+ can go through* and so basically that allows the protons to slide back down into the matrix so a proton uncoupler allows H+ to get back to the matrix without going through ATP synthase* big deal becuase then do not get same atp yield with another way back through matrix
c- no makes it less acidic becuase allowing H+ to leave. Cyanide acts on Cytochrome C, but dinitrphenol works along the membrane all the way down making holes it allows the membrane to become veyr leaky*
- The enzyme glucose 6- phosphatase catalyzes the hydrolysis of glucose 6-phosphate to glucose. Which of the following is true statement about that reaction?
a. it involves the hydrolysis of a phosphoester bond
b. it involves positive free energy change
c. it occurs in muscle cells
d. it occurs early in the process of glycogenesis
a. it involves the hydrolysis of a phosphoester bond- TRUE this bond links two sugars of a nucelic acid*
b. it involves positive free energy change- no it is not positive it is negative delta G free energy change
c. it occurs in muscle cells- no occurs mostly in the liver
d. it occurs early in the process of glycogenesis- no occurs at the end**
A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The “bond” involves this linkage C-O-PO2−-O-C. Discussion of phosphodiesters is dominated by their prevalence in DNA and RNA, but phosphodiesters occur in other biomolecules, e.g. acyl carrier proteins.
Phosphodiester bonds make up the backbones of DNA and RNA. The phosphate is attached to the 5’ carbon. The 3’ carbon of one sugar is bonded to the 5’ phosphate of the adjacent sugar.Specifically, the phosphodiester bond links the 3’ carbon atom of one sugar molecule and the 5’ carbon atom of another (hence the name, 3’, 5’ phosphodiester linkage).
Gluconeogenesis Steps 2
The big thing you can’t use for glucogeneosis is acetyl-co a or immediate breakdown products of that, but you can use carbs, oxaoloacate some amino acids if take the amino group off then can use them* definitely don’t need to memorize which amino acids have right carbon skeleton to feed into this too much detail, but just know some amino acids if deaminate them take off amino group can do this to
Key beginning difference besides cannot start with acetyl-Coa= start with pyruvate to phosphoenolpyruvate step, very very negative delta G reaction highly exothermic, energetically really really expensive to climb back up hill to phosphoenolpyruvate, so cells have evolved to do it in two steps, first made into oxaloacetate then oxaloacetate then made into phosphenolpyruvate*
- When ppl talk about gluconeogenesis being energetically expensive pointing to this, need 2 atps for that first step and 2 gtps for second step, that is a BIG energy investment*
condensation rxns vs hydrolysis
lipases break apart bonds by adding a water molecule across bonds, so do this in small intestine*
proteases break down things through hydrolysis by adding a water molecule BIG PICTURE TERM THEY LOVE TO USE** be aware of all the things that fall under these umbrellas* hydrolsis anytime add a water to break one of these bonds, condesnation anytime take away a water molecule
glycerol forming…
lipases fundamentally adding H20 across double bond to break fatty acids and make glycerol
