DENT 730A Lecture 2: Bioenergetics and Carbohydrate Metabolism

Flashcards cover key concepts from Lecture 2: Bioenergetics, electron transport chain, and carbohydrate metabolism, including glycolysis, TCA, gluconeogenesis, glycogen metabolism, PPP, sugar digestion/absorption, and glycan-containing biomolecules.

What is Bioenergetics?

The study of energy transformations in biological systems; it PREDICTS whether a process is spontaneous (favorable) or non-spontaneous (unfavorable) based on Gibbs free energy change (ΔG).

What are the three factors that affect bioenergetics?

Enthalpy (ΔH), Entropy (ΔS), and Free Energy (energy avaiable to do chemical work) (T); ΔG = ΔH − TΔS.

Define ΔG, ΔH, and ΔS T

ΔG: change in free energy (energy available to do work); ΔH: change in enthalpy (heat released or absorbed); ΔS: change in entropy (disorder). and heat

What does a negative ΔG signify?

A spontaneous (favorable) reaction.

Difference between ΔG and ΔGo

ΔGo is the standard free energy change (@1 mol/L 298K and 1 ATM) (a baseline when comparing reactions under standard a standard state)

ΔG is free energy

Standard free energy of hydrolysis of ATP?

-7.3 kcal/mol

Explain the chemiosmotic hypothesis.

Energy from electron transport pumps protons across the inner mitochondrial membrane from matrix into INTERMEMBRANCE space creating a gradient from NADH and FADH2 donate a pair of electron protons flow back through ATP synthase (F1F0) to synthesize ATP (oxidative phosphorylation) (series of redox reaction)

Where is the electron transport chain located and Kreb Cycle?

ETC located in the inner mitochondrial membrane

Kreb Cycle - matrix

Complex 1

NADH Dehydrogenase enzyme transfer of electrons from NADH to the electron transport chain. (NADH is from Kreb Cycle)
E is transferred to CoQ

Complex 2

Does not Span the membrane but is attached

Succinate Dehydrogenase Succinate to Fumarate
Electrons from FADH2 transfered to Coenzyme Q

Coenzyme Q

Accepts E and proton from both complez 1 and 2 then transfers to Complex 3

Complex 3 and 4

E are passed to Cytochome C to complex 4 then at 4 it O2 is reduced to water. O2 is the final E acceptor

How many ATP are produced per NADH and per FADH2 in the ETC?

Approximately 2.5 ATP per NADH (1 NADH = 10 Proton and C4 = 4 Proton = 2.5 thus 10/4) and 1.5 ATP per FADH2.

What ROS are produced in the ETC and what enzymes defend against them?

Reactive oxygen species such as superoxide and hydroxyl radical can damage cells; defenses include superoxide dismutase, catalase, and glutathione peroxidase.

What is the ETC inhibited by?

Electron flow and ATP synthesis are inhibited because oxidative phosphorylation is tightly coupled to the ETC.( Amytal Rotenone, antimycin A and CN CO H2S NaN3)

Where is the normally more H+

More H+ in the intermembrance space so pumping H+ in there makes a strong proton gradient

Uncoupling Proteins (UCP)

Inner membrane allows H+ but NO ATP is made this energy is called heat and is released through a process known as non-shivering thermogenesis.

Racemases

Enzyme that can inverts D- and L-Isomers the furthest chircal carbon from hydroxl group determines the isomer

Digestion of Carbs Final Products

Final Products: Glucose, galactose and fructose are broken down to monosac and absorbed in small intest.

Where does digestion begin

Begins in mouth

Difference between Starch and Glycogen and its branches

Starch (Plants) can be in amylose (straight chain) or Amylopectin (branched)
Animal (glycogen)

How is cellouse broken down

By Salivary amylase breaking a(1’4) bonds but humans dont have B(1’4) thus we lack the enzyme endoglucosidase to break down it

How and what transport glucose into the cell

GLUT 2 found in pactreatic B cell and live and kidney transporter moving outside the cell
GLUT 4 is in adipose tissue and skelemuscle but is insulin dependent bringing it in

Sodium dependent glucose linked transporter (SGLT) pumps against concen gradient pumps fructose glucose and galatacose into epitehlia cells of the intestine

Abnormal Degradition of disaacharides

only monosac are digested and abnormalilties of dissach break down occurs leading to water being drawn causes diarreah and bacterial fermanation

Lactase Deficency

Lactase intolerance leading to lactose being unbroken into galactose + glucose which leads to bacteria fermneting this and relasing H2 which leads to methane (farts)

Carbohydrate Metabolism Chart

1st Irreversible step of Glycolysis

Hexokinase phosphorlyzes glucose turning it to G6P
Glucokinase is a derivative that has a higher vmax and km than hexokinase 1-3 allowing it handle more and lower affinity

these enzymes are inhibited by G-6-P thus preventing any feedback and committing it into cell membrane

Step 3 of glycolysis (reg. Step)

F6P into Fructose 1’6 by PFK-1 MOST important control point because it commits to glycolysis

What is the fate of pyruvate under aerobic conditions?

Pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex and enters the TCA cycle, generating NADH.

What are the components and cofactors of the Pyruvate Dehydrogenase (PDH) complex?

E1 (pyruvate dehydrogenase), E2 (dihydrolipoyl transacetylase), E3 (dihydrolipoyl dehydrogenase); cofactors include thiamine pyrophosphate (TPP), lipoic acid, CoA, FAD, and NAD+. Arsenic can inhibit lipoic acid–containing enzymes.

How does arsenic poisoning affect energy metabolism?

Affects step #6 (oxidation of G3P) where NADH is made. Asenic competes with Pi for G3P deydrogronease, which leads to 3-Phophoglveryate formation directly leading to NADH made but not ATP made losing an ATP pay off phase

Step 9 of Glycolysis

2-Phosphoglycerate is dhydrated to pep by Enolase

enolase can be inhibited by fluoride

Fate of Pyruvate

can go to aerobic metobolism and anaeorbic making lactate or ethanol

Step 10 (reg step)

Phosphoenolpyruate PEP is converted to pyruvate by the enzyme pryruatcute kinase which is irresible and ATP is made in this step too

Pyruvate Dehydrogenase

the enzyme that coverts pyruvate to acetly CoA when it enters the mitochondrial matrix NaDH is reduced and Co2 is released

PDH coenzymes deficiencies

E1 Pyruvate dehydrogenase can be deficient due to lack of TPP from B1 vitamins leading to pyruvate being shunted to lactic acid ferm which auses congential lactic acidosis

What is the rate-limiting step of the TCA cycle?

Isocitrate dehydrogenase is one of the rate-limiting steps that is irrevisble and catalyzes the conversion of isocitrate to alpha-ketoglutarate producing NADH and CO2

Oxidation of Succinate

Succinate is oxidized to fumarate by succinate dehydrogease and FAD is reduced to FADH2
ONLY Enzyme embedded in the inner mitochondrial membrane (attached to complex 2 of ETC)

What is the first committed step of the TCA cycle?

Citrate synthase catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate.

Highest regulated enzymes in TCA

Citrate synthease
Isocitrate dehydrogenase
a-ketoglutarate dehydrogenase complex

Where does gluconeogenesis predominantly occur during an overnight fast, and what percentage is in the liver?

Predominantly in the liver; about 90% in the liver and 10% in the kidneys.

What are the primary substrates for gluconeogenesis?

Glycerol, lactate, and glucogenic amino acids.

Which enzymes bypass irreversible glycolytic steps in gluconeogenesis?

Pyruvate carboxylase (REQUIRES ATP) to ooxaloacate then PEP carboxykinase bypass the pyruvate kinase step fructose-1,6-bisphosphatase bypasses PFK-1; glucose-6-phosphatase bypasses hexokinase/glucokinase.

What are the substrates for gluconeogenesis listed in the notes?

Glycerol, lactate, and amino acids.

Glycerol Kinase

Glycerol is converted to G3P and then to DHAP (both in glycolysis and glucneo) wihch is only in the liver and is not in Adipocytses because it lacks the enyzme.

Cori Cycle

Lactate is released into the blood by muscles and liver and through rbc which is converted by lactate dehydrogenase into glucose

amino acid as a substrate for gluconeogensis

Muscle protein like Alanine Serine Glycine Cysteine and Throeonine can be converted to NH3 then to glumatate to alanine which can enter gluconeo

amino acids are converted to oxaloacetate

Formation of glucose from G-6-P

Glucose 6 Phosphatase oonly found in live and kindney converts G6P to glucose

Reg. of Gluconeogensis

Horomoes such as glucagon from a-cells of pancreatic stimulate

Main stores of glycogen?

liver and skeletal muscle

fluctuation of glycogen

liver glycoen stores increase during the well fed state and are depleted during a fast

muscle glyocgen is not affected by short period of fasting and is synthesized to replensih muscle stores after a strenous excersise

What is glycogenesis and where does it occur?

syntheszizd from alpha d glucose involves G6P to G1P, UDP-glucose, glycogenin primer, glycogen synthase, and branching enzyme.and occurs in the cytosol

Phosphoglucomutase

synthesis of glucose 1-phosphate from G-6-P in glycogensis

Synthesis of UDP-glucose

UDP-glucose pyrophorylase converts glucose1-phosphate to UDP-glucose, which is more reactive than glucose

Glycogen Synthase

converts UDP-glucose to UDP which needs glycogenin as a primer and releases a glycogen

What enzyme forms branches in glycogensis

amylo a 1’4 and a(1,6)transglcosidase forms branches. 1’6 banches and removes a chain from non reduncing end after 6-8 residues added on by amylo

How is glycogen metabolism hormonally regulated in the liver and muscle?

Glucagon and epinephrine stimulate glycogenolysis; insulin stimulates glycogenesis. Glycogen synthase is inactivated by phosphorylation (kinases) and reactivated by protein phosphatase-1. Allosteric regulation aligns with energy/nutrient status.

Which enzyme cleaves off a(1’4) glycosidic chain

glycogen phosphorylase releases glucose at nonreudcing ends. You get glucose 1-phosphate + phosphate from it

What enzyme cleaves off 1 branch of 1’6

Amylo-a(1’6) glucosidase removes the single remaining releasing it as free glucose

How is g-6p converted in liver and muscles

g-6-p is conoverted to glucose my glucose-6-phosphatase in the liver and in the muslces g-6p cannot be dephosphoryed bc of the lack of the enzyme thus it ends glycolysis

Von gierke disease

a defienciy of glucose 6 phosphateases which cuases glycogen storage disease in type 1 diebetes leading to inability of liver to provide free glucose during a fast.

Regulation of Glycogen synthesis and degradation

Liver: Glycogenesis accelerates during periods where the body has been well fed
Glycogenolysis accelartes during periods of fasting

Muscle: glycogenolsis occurs during active exercise
glycogensis begins as soon as the muscle is again at rest

Hormonal regulation of Glycogen synthesis and degradation

glucagon stimulates glycogenlysis and inhibits glycogensis

epinephrine stimulates glycogenlysis and inhibits glycogensis

insulin stimulates glychoensis and inhibits glycogenolysis

Active Form of Glycogen synthesis and degradation

Active form of Glyocgen degradtion is when Glycogen Phosphorylase is activated by ATP

Deactive form is Glycogen phosphorlase B when Protein phosphate 1 removes the phosphate from a signal from insulin leading

how does glucose and galatose get into the cell

sodium -glucose transporter and leave by glut 2

how does fructose get into the cell

Glut 5

composition of Malatose, sucrose, lactose

malatose - two gluclose
sucrose - glucose + fructose
lactose - glucose + galatcose

what is Hexose monophosphate shunt

PP pathway

Glucose-6-Phosphate dehydroganse

Enzyme that catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate in PP pathway relasing NADPH

6-phosphateglucoante Dehydrogenase

Enzyme that catalzyed 6-phosphogluconate to ribulose 5 phosphate releasing NADPH in PPP

How is nucleic acid biosynthesis made

ribose 5 phosphate is the precurors when added with a 2c chain in PPP

NADPH function

used in fatty acid synthesis, reduction of h2O2, and reduction of one Oxygen to h2o, and maitain hemoglobin in its reduce form and protects agreats hemolysis

What is the most common disease causing enzyme abnormaily in humans

Glucose-6-phosphate dehydrogenase defiency which impairs the ability of RBC to form NADPH and this is done by glutatione reductase then go through Glutathione peroxidases to convert the oxidant stress of H2O2 and convert to 2H2o

h2o2 is detrimental to red blood cells, leading to hemolytic anemia when deficiency occurs.

What are glyococojungates

important molcules of the ECM that need to be turnover by lysosomes if not it could to defeictive degreading resultsing in storage diseases such as mucopolysacchirdoses and ologiosacchinesdose

What is the difference between GAGs, proteoglycans, and glycoproteins?

GAGs are linear, negatively charged polysaccharides in the ECM;

Proteoglycans are core proteins with GAG side chains;

Glycoproteins are proteins + oligosaccharide chains that are branched

What diseases are associated with degraded lysosomal hydrolases acting on GAGs?

Mucopolysaccharidoses (MPS) and oligosaccharidoses; accumulation of GAGs leads to skeletal/ECM abnormalities and other symptoms.

What is the Pentose Phosphate Pathway and what are its key products?

A pathway of glucose-6-phosphate in the cytosol that generates NADPH and ribose-5-phosphate; important for reductive biosynthesis and nucleotide synthesis.

Which enzymes are key in the oxidative phase of the PPP and what is the consequence of their deficiency?

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase generate NADPH; G6PD deficiency impairs RBC protection from oxidative stress.

How are NADPH and ribose-5-phosphate used in cells?

NADPH provides reducing power for biosynthesis and antioxidant defense; ribose-5-phosphate is used for nucleotide synthesis.

What are the three classes of carbohydrate-derivative structures discussed and how do they differ?

Glycosaminoglycans (GAGs) – linear polysaccharides; Proteoglycans – core protein with GAG chains; Glycoproteins – proteins with short oligosaccharide chains.

What is the role of anomeric carbon and the difference between α- and β-anomers in cyclized monosaccharides?

Cyclization creates a new chiral center at the anomeric carbon (C1 for aldoses). α- and β- refer to the position of the anomeric hydroxyl relative to the CH2OH group (α typically on the opposite side to CH2OH in Haworth projection; β on the same side).