biochem 2 Flashcards
What is bioenergetics?
the thermodynamics of biological systems
living systems must maintain a ___ state
NON-equilibrium
What is the dynamic steady state?
describes the ability of living things to maintain a constant, steady internal environment that is NOT in equilibrium with its surroundings
What is the difference between ΔG(degree sign) and
ΔG(degree sign)’?
both represent a standard state “from-the-textbook-table” value for Gibbs free energy calculated at a point where we have the exact same concentrations of all species, both products and reactants (i.e., Q = 1). Just remember that the prime (’) symbol means it is at physiological pH too.
What is the formula for change in free energy in biological systems?
ΔG=ΔG’+RTlnQ
Q- reaction quotient
Think of ΔG’ as the fixed, unchangeable value, and of ΔG as the variable one
What is the relationship between standard free energy change and equilibrium constant?
ΔG’= -RTlnKeq
endergonic = ΔG is \_\_\_ = \_\_\_\_ exergonic = ΔG is \_\_\_ = \_\_\_
positive, non-spontaneous
negative, spontaneous
T/F? If Keq =1, ΔG=0
true (If Keq = 1 then ΔG = 0, since ΔG = -RTlnKeq, and the ln(1) = 0)
very rare case
T/F? If Keq =Q, ΔG=0
true, the reaction is in equilibrium
ΔG(degree)’ for ATP hydrolysis «_space;__
0
around -30.5 kJ/mol
AMP -> cAMP is a __ reaction
endergonic
Why is the hydrolysis of ATP so exergonic?
the bonds between phosphates are highly energetic because at a physiological pH, the oxygens are negatively charged and repel each other. resonance stabilization and repulsion make ADP and Pi more stable than ATP
What is substrate-level phosphorylation?
Formation of ATP from ADP in which the source of the necessary phosphate is a phosphate bound to another molecule (i.e., the “substrate”). To proceed, this process MUST be coupled to an exergonic reaction
Where does substrate level phosphorylation occur?
primarily in the cytosol (part of glycolysis)
BUT also in matrix of mitochondria where GTP is formed during the CAC
What is oxidative phosphorylation?
Formation of ATP out of ADP and Free Organic Phosphate (Pi) by harnessing the energy of the proton gradient across the inner mitochondrial membrane. This proton gradient is created as a result of coupling the oxidation of high- energy molecules such as NADH and FADH2 to the pumping of protons.
Where is oxidative phosphorylation located?
in mito matrix
ATP hydrolysis is almost always ___ to another reaction process
coupled
phosphorylation using ATP is a major human body _____
regulatory mechanism
(Many enzymes, proteins, and signaling molecules are turned “on” or “off” by the process of phosphorylation via a phosphoryl group transfer)
What is reduced and what is oxidized in this reaction?
GADP + NAD+ + Pi→1,3-BPG + NADH
In the reaction, GADP is the reduced form, NAD+ is the oxidized form 1,3 BPG is the oxidized form, and NADH is the reduced form. Thus NAD+ is being reduced (it is an oxidizing agent) and GAPD is being oxidized (it is a reducing agent).
When you see: NADH/NAD+, NADPH/NADP+ FADH2/FAD, FMNH2/FMN, semiquinone, ubiquinone, or cytochrome think ___
REDOX!!
What is the difference between aerobic and anaerobic respiration?
Aerobic respiration uses oxygen as the final electron acceptor
anaerobic respiration uses a molecule other than oxygen
(refer to lactic acid cycle in muscle or fermentation)
facultative anaerobes prefer __
facultative aerobes prefer __
anaerobic conditions
aerobic conditions
What are the steps for glycogen metabolism?
1) Glycogen phosphorylase removes glucose residues from the reducing ends of glycogen polymers → Glucose-1P
2) Phosphoglucomutase converts Glucose-1P → Glucose-6P (G-6P is then funneled into the 2nd step of GLY)
Where does fructose metabolism occur?
muscles, kidneys and liver
How is fructose converted to an intermediate of glycolysis in the muscles and kidneys?
Hexokinase converts Fructose → Fructose-6P (F-6P is then funneled into the 3rd step of GLY)
how does fructose get converted to an intermediate of glycolysis in the liver?
1) Fructokinase converts Fructose → Fructose-1P
2) Fructose-1-phosphate aldolase converts Fructose-1P → Glyceraldehyde-3P + Dihydroxyacetone-P (DHA-P)
3) Triose phosphate isomerase converts DHA-P → Glyceraldehyde-3P (GA-3P is then funneled into the 5th step of GLY)
What is the steps of galactose metabolism?
In multiple steps (UDP = coenzyme) Galactose is converted → Glucose-1P
• Phosphoglucomutase converts Glucose-1P → Glucose-6P
(G-6P is then funneled into the 2nd step of GLY)
Give an explanation for the fact that erythrocytes use fermentation to convert pyruvate into lactate, even in the presence of oxygen
RBCs dont have mitochondria
What is unique about ethanol fermentation?
pyruvate is broken down into ethanol and CO2
In lactic acid fermentation what is produced and what is the final electron acceptor?
lactate is produced and is the final electron acceptor
Why is fermentation important?
it regenerates NAD+ so that glycolysis can continue. NAD+ regeneration is necessary for both human fermentation during oxygen debt and yeast/bacterial fermentation.
What is gluconeogenesis?
reversal of glycolysis to produce glucose from pyruvate. However, three glycolytic enzymes are substituted for four unique enzymes specific to gluconeogenesis.
gluconeogenesis occurs in the __, in response to ___
liver, low blood sugar
The four enzymes specific to gluconeogenesis replace three glycolytic enzymes which all catalyze _________ reactions.
catalyze irreversible reactions. Those three steps that are replaced are all phosphorylation reactions.
When you see the pentose phosphate pathway think __
1) NADPH synthesis and 2) Ribose-5-Phosphate (R5-P).
What is NADPH?
reducing agent (NADPH → NADP+) used during “Reductive Biosynthesis”—a general term referring to a large number of reactions used to synthesize fatty acids and sterols. NADPH is also necessary for the production of Glutathione, the most important antioxidant in counteracting the damaging impact of the peroxide and radical byproducts of oxidative respiration.
What is R5-P?
used to synthesize nucleotides. It is the oxygen-bearing ring of all nucleotides, including the famous deoxy-ribo-nucleic acid.
What happens in the oxidative phase of PPP?
Glucose-6-P → 6-Phosphogluconate → Ribulose-5-P
The two steps outlined above are both coupled to the conversion of NADP+ to NADPH.
NADPH is used to: 1) reduce glutathione disulfide (GSSH) to glutathione (2GSH) and 2) act as a cofactor for reductive biosynthesis.
What happens in the non-oxidative phase of the PPP?
Ribulose-5-Phosphate→R5-P SUGARPOOL Glucose-6-Phosphate
SUGAR POOL = Erythrose-4-P, Sedoheptulose-4-P, Xylulose-5-P, and a number of other carbohydrates you do NOT need to know by name for the MCAT.
R5-P is funneled into nucleotide synthesis. (Note that R5P and Ribulose-5-Phosphate are two different molecules).
How many NADPH are produced per glucose-6-P molecule by the PPP? How many glutathione molecules are produced per glucose-6-P?
For each glucose 6-phosphate, two NADPH molecules are generated
four glutathiones are generated
What is the PDH complex?
Pyruvate → Acetyl-CoA Think of the PDH complex as the linkage between glycolysis and the Citric Acid Cycle. It is a set of three enzymes that convert pyruvate to acetyl-CoA, which is the first substrate of the Citric Acid Cycle.
What are the 3 destinations for pyruvate?
PDH Complex → Acetyl-CoA
Lactate Dehydrogenase → Lactate
Pyruvate Carboxylase → Oxaloacetate
How many Co2 are produced in the CAC?
2 CO2 per cycle
What is the starting and ending product of the CAC?
2 Acetyl CoA 6 NADH 4 CO2 2 FADH2 2 ATP
How many ATP molecules will 1 NADH generate? FADH2?
NADH- 3 ATP
FADH2 - 2 ATP
Why is the malate aspartate shuttle needed?
NADH cannot pass through the inner mitochondrial membrane. Therefore, NADH produced from glycolysis cannot enter the ETC without the help of this shuttle.
How does the malate - aspartate shuttle transport NADH across the inner mito membrane?
NADH donates two electrons to oxaloacetate (OAA) converting it to malate. Malate passes into the matrix via the MALATE-alpha-KETOGLUTARATE ANTIPORTER. Inside the matrix, malate is converted back into OAA, regenerating NADH. OAA is then converted into aspartate so that it can be pumped back into the cytosol via the GLUTAMATE-ASPARTATE SHUTTLE.
Why do we need a G3P shuttle?
NADH can’t enter the mitochondria to participate in ETC
How does the G3P shuttle work?
donates two electrons to dihydroxyacetone phosphate (DHAP) to form Glycerol-3-Phosphate (G3P). G3P is converted back into DHAP by Mitochondrial G3P dehydrogenase, an enzyme bound to the cytosolic surface of the inner mitochondrial membrane. The enzyme passes the electrons to FAD to form FADH2.
Why do we need the carnitine shuttle?
fatty acids can’t pass through the inner mito mem to go through beta-oxidation
How does the carnitine shuttle work?
The enzyme carnitine acyltransferase attaches the fatty acyl group from an acyl-CoA to the hydroxyl group of carnitine. A translocase enzyme on the inner mitochondrial membrane moves one acyl-carnitine into the matrix and one carnitine back out.
Why is the citrate-acetyl-CoA shuttle important?
during periods of energy abundance, acetyl-coA groups in the mitochondria are redirected from the CAC to fatty acid synthesis. (acetyl-CoA can’t pass thru inner mito mem)
how does the citrate acetyl-CoA shuttle work?
Acetyl CoA is combined with OAA to form citrate. citrate passes through inner mito mem, and is converted back to OAA and acetyl-coA in the cytosol
What is chemiosmotic coupling in terms of ATP synthase?
The direct coupling of the energy inherent in the electrochemical gradient across the inner mitochondrial membrane to the phosphorylation of ADP (to form ATP).
Suppose a localized change in temperature decreased the free energy released by a proton traveling through the F0 moiety of ATP synthase. What would be the likely effects on: a) ATP production, b) ETC function, c) the strength of the electrochemical gradient, and d) the Citric Acid Cycle
a) decrease ATP production bc the equilibrium shifted so phosphorylation of ADP happens at slower rate
b) ETC will slow down bc there wont be as many protons to be pumped by complexes 1,3 and 4
c) electrochemical gradient will slightly increase bc ATP synthase is slower
d) CAC will not be affected
__ is an allosteric inhibitor of Phosphofructokinase-1
ATP
allosteric regulator molecules ALWAYS bind __
away from the active site
Where is cortisol produced?
adrenal cortex
glucocorticoids have a ___ effect on metabolism
“glucagon-like”
also reduce inflammation
What are examples of catecholamines?
dopamine, epinephrine and norepinephrine
epinephrine and norepinephrine have a ___ effect on metabolism
“glucagon-like”
rapid mobilization of energy stores necessary for the fight or flight response
What effect does T3 and T4 have on metabolism?
increase basal metabolic rate; both are secreted by the thyroid in response to TSH from anterior pituitary
What molecules up regulates and down regulates glycolysis?
PFK-1 inhibited by ATP
Hexokinase is inhibited by glucose-6-P
pyruvate kinase is inhibited by ATP and alanine
AMP is the upregulator
What molecules upregulate and down-regulate gluconeogenesis?
(OPPOSITE OF GLYCOLYSIS)
F-1,6-BP is inhibited by AMP and stimulated by ATP
both pyruvate carboxylase and PEP inhibited by ADP
What molecules up-regulate and down-regulate the process of glycogenolysis?
glycogenolysis (the breakdown of glycogen into G6P)
stimulated - glucagon and epinephrine in bloodstream (both stimulate a cAMP cascade, which activates protein kinase A, which phosphorylates phosphorylase kinase, which activates glycogen phosphorylase
inhibited - w/out epinephrine and glucagon
What molecules up-regulate and down-regulate glycogen synthesis?
inhibitors - glucagon and epinephrine (bc pka phosphorylates glycogen synthase -inactivating it)
stimulate- cAMP cascade is withdrawn, protein phosphorylase 1 will dephosphorylate glycogen synthase
what molecules stimulate and inhibit the CAC?
pyruvate dehydrogenase complex is the entry point of CAC
PDC is inhibited by acetyl-CoA and NADH, ATP
stimulated - low levels of ATP and NADH
isocitrate dehydrogenase is stimulated by ADP and inhibited by ATP and NADH
alpha-ketoglutarate dehydrogenase is inhibited by its products, succinyl-CoA and NADH, and ATP
What molecules stimulate and inhibit the ETC?
stimulate - ADP
inhibited - ATP
What molecules stimulate and inhibit the pentose phosphate pathway?
stimulate - low level of NADP+
inhibit - high level of NADP+
where does beta-oxidation of fatty acids occur?
mito matrix (exception - extra long chain fatty acids first enter a peroxisome)
what molecules does beta-oxidation require?
1 FAD
1 H2O
1 NAD+
1 CoA-SH
What are the net results of each 2-carbon cycle of beta-oxidation?
1 FADH2 (2 ATP) 1 NADH (3 ATP) 1 Acetyl-CoA (12 ATP)
How many cycles of β-oxidation will be required to completely oxidize a 14-carbon fatty acid? How many cycles will be required to oxidize a 17-carbon fatty acid?
To determine how many rounds of β-oxidation is required to oxidize an even numbered fatty acid, simply divide the number of carbons by 2 and subtract 1. So for a 14-carbon fatty acid, 6 rounds of β-oxidation are needed. This is because every round cleaves 2 carbons off. At the end, a final round cleaves the 4-carbon fatty acid into two 2-carbon fatty acids, finishing the oxidation.
For an odd numbered fatty acid, subtract 1 to get to an even number. Then divide by 2, subtract 1. So for a 17-carbon fatty acid, 7 rounds of β-oxidation are needed (17-1=16. 16/2=8. 8-1=7). This is because every round cleaves off two carbons, but at the end of an odd numbered fatty acid, the final round cleaves the 5-carbon fatty acid into one 2-carbon fatty acid and one 3-carbon fatty acid.
What is the difference between beta-oxidation in unsaturated fatty acids?
enoyl-CoA isomerase catalyzes the movement of double bonds to the 2-3 position
if there is a conjugated bond, a pair of enzymes will delete one of the two double bonds and then enoyl-CoA isomerase moves the remaining double bond to the 2-3 position
what are the 3 ketone bodies?
acetone, acetoacetate (energy), 3-hydroxybutyrate (energy)
Why are ketone bodies formed?
formed by liver during prolonged fasting periods as byproducts of increased fatty acid metabolism
cause KETOACIDOSIS (excess acidity of blood)
what is transamination?
A key step in protein metabolism for energy is transamination of amino acids—or the exchange of an amine group on one molecule for a carbonyl group on another.
what amino acids are ketogenic? What amino acids are both ketogenic and glucogenic?
keto - leucine and lysine
both - isoleucine, phenylalanine, tryptophan, tyrosine, and threonine
What is the difference between ketogenesis and ketolysis?
ketogenesis is the process by which ketone bodies produced through the breakdown of fatty acids (occurs in liver)
ketolysis - utilization of ketone bodies by converting them to acetyl CoA for energy (occurs in heart and brain)
brain only uses ___ as fuel
glucose (ketones if fasting)
cardiac muscle uses __ as fuel
fatty acids (ketones in starvation)
RBCs use what as fuel?
ONLY glucose
threshold for weight gain is __ than for weight loss
lower
How many calories are in one gram of a) fat, b) protein, c) carbohydrate?
fat - 9 kcal/g
carb - 4 kcal/g
protein - 4 kcal/g
fatty acid synthesis is always the construction of a __
palmitic acid
