BIOENERGETICS

Biologic systems are essentially​ isothermic ​and use chemical energy to power living processes.

Entropy​ = is the extent of ​disorder or randomness​ of the system and becomes maximum as equilibrium is approached.
Enthalpy​ ( Heat ) = the ​internal energy​ of a system plus the product of the pressure and volume of the system.
Gibbs change in F​ree energy (ΔG) =​ portion of the total energy change in a system that is available for doing work.
Also known as the ​chemical potential.

Law of thermodynamics:

1​st:​ ​The total energy of a system, including its surroundings, remains​ constant​.(​ “Energy is neither lost nor gained.” )

( However, energy may be​ transferred ​from one part of the system to another, or may be
transformed​ into another form of energy. )

2​nd: ​The total ​entropy of a system must increase ​if a process is to occur spontaneously.

“ΔG = ΔH−TΔS”​ ( ΔG= free-energy change, ΔH= is the change in enthalpy,

T =absolute Temperature, ΔS= change in entropy )

( This formula shows the relationship between the free-energy change (ΔG) of a reacting system
and the change in entropy (ΔS) Under conditions of constant temperature and pressure )

​If ΔG is negative​ = reaction proceeds with ​loss​ of free energy = ​Exergonic

​If ΔG is positive ​= reaction proceeds only if free energy can be​ gained​ = ​Endergonic.
​ If ΔG is zero​ = the system is at​ equilibrium​ and no net change takes place.

ENDERGONIC PROCESSES PROCEED BY​ COUPLING ​TO EXERGONIC PROCESSES

The terms exergonic and endergonic, rather than the normal chemical terms​ “exothermic”​and ​“endothermic,”​ are
used to indicate that a process is accompanied by loss or gain, respectively, of free energy in any form, ​not necessarily
as heat.

Fig 11-1 metabolite A to metabolite B occurs with release of free energy

and is coupled to another reaction in which free energy is required
to convert metabolite C to metabolite D.

The exergonic reactions are termed​ catabolism​ (generally, the​ breakdown or oxidation​ of fuel molecules), whereas the
synthetic reactions that ​build up​ substances are termed ​anabolism.​ ( Catabolism + anabolism = Metabolism )

Autotrophic organisms​ = utilize ​simple exergonic processes.​ Ex Sunlight

Heterotrophic organisms =​ obtain free energy by coupling their metabolism to the breakdown of complex
organic molecules​ in their environment.

hydrolysis of the terminal phosphate of ATP divides two groups:

1. Low-energy phosphates ​= found in the intermediates of glycolysis, have G0′ values ​smaller than that of ATP.
2. High-energy phosphates​ = the value is ​higher than that of ATP.
HIGH ENERGY PHOSPHATES ​= “​ENERGY CURRENCY​” OF THE CELL
“​ATP​” is able to act as a ​donor​ of high-energy phosphate
“​ADP​”​ accept ​high-energy phosphate to​ form ATP​ (ATP/ADP cycle)

3 Major sources ​of High energy phosphate taking part in energy conservation or energy capture:
1. Oxidative phosphorylation
2. Glycolysis
3. The Citric acid cycle

BIOLOGIC OXIDATION

Oxidation​ = the removal of electrons

Reduction​ = gain of electrons
Oxidoreductases =​ enzymes involved in oxidation & reduction

Free energy change is​ proportionate​ to the tendency of reactants to donate or accept electrons. Thus free energy
change in terms of ΔG0′, can be expressed numerically as an ​oxidation-reduction or redox potential (E′0)​.

4 groups ​of oxidoreductases:

a. Oxidases - ​catalyze the ​removal of hydrogen​ from a substrate using o ​ xygen as a hydrogen acceptor​.
Ex. Cytochrome oxidase, Flavoproteins (FMN & FAD )
b. Dehydrogenases - Cannot​ use oxygen oxygen as a hydrogen acceptor.
- 2 main functions :
​* Transfer of hydrogen​ from one substrate to another in
a coupled oxidation–reduction reaction.
* ​Transfer of electrons in the respiratory chain​ of electron
transport from substrate to oxygen.
-utilizes common coenzymes or hydrogen carriers such as ​NAD+ ​( formed from ​niacin​ )
-When a substrate is oxidized, it​ loses​ 2 H+ atoms and 2 e- then 1H+ and both electrons are ​accepted​ by NAD+
to form NADH​ and the other H+ is released. ( this occurs in glycolysis, & citric acid cycle )
-​Other Dehydrogenases ​depend on Riboflavin ,the flavin groups such as ​FMN and FAD:
*riboflavin-linked dehydrogenases​ are concerned with ​electron transport​ in (or to) the respiratory chain.
(Ex. “​NADH dehydrogenase”​ - acts as a carrier of electrons between NADH and the
components of higher redox potential
-​Cytochromes​ May Also Be regarded as Dehydrogenases. ( iron-containing hemoproteins )

c. Hydroxyperoxidases ​- role in ​protecting the body ​against the harmful effects of reactive oxygen species (ROS).
-Uses hydrogen peroxide or organic peroxide a substrate
- 2 types of enzyme :
* ​Peroxidases- ​reduces hydrogen peroxide (Ex.in RBC ​glutathione peroxidase;​ catalyzes
the destruction of H2O2 )

* ​Catalase ​- can act as a peroxidase. also able to catalyze the breakdown of H2O2
formed by the action of oxygenases to H20 & O2

d. Oxygenases ​- catalyze ​direct transfer & incorporation of O2​ into a substrate molecule.
- ​2 steps​ in transfer & incorporation of O2:
1​st​ : oxygen is bound to the enzyme at the active site.
2​nd​ : the bound oxygen is reduced or transferred to the substrate

-​ 2 subgroups​:
1. Dioxygenases -​Incorporate​ Both Atoms​ of Molecular Oxygen into the Substrate
Ex. Homogentisate diooxygenase
 2. Monooxygenase ​- ( ​Mixed-Function​ Oxidases, Hydroxylases) Incorporate​ Only
One Atom​ of Molecular Oxygen Into the Substrate.
Ex. Cytochrome P450

Cytochrome P450 -​ Important in ​Steroid Metabolism​ & for the ​Detoxification​ of Many Drugs.
-​ Mitochondrial cytochrome P450​ systems are found in steroidogenic tissues and are concerned
with the biosynthesis of steroid hormones from ​cholesterol.

Superoxide Dismutase - protects ​aerobic organism against oxygen toxicity.

- single electron to O2 generates the potentially damaging​ superoxide anion free radical​ (O2 ), which gives
rise to free-radical chain reactions, superoxide dismutase (SOD), the enzyme responsible for
its ​removal in all aerobic organisms​ ,indicate that the​ potential toxicity of oxygen​ is due to
its conversion to superoxide.

RESPIRATORY CHAIN & OXIDATIVE PHOSPHORYLATION

The Mitochondrial matrix is enclosed by a​ double membrane.
- outer membrane = permeable​ to most metabolites ; enzymes = acyl-CoA synthetase and glycerolphosphate
acyltransferas

- ​Intermembrane space​= enzymes ; adenylyl kinase and creatine kinase

-​ inner membrane​ = ​selectively​ permeable ; enzymes = enzymes of the respiratory chain, ATP synthase, and
various membrane transporters. ( Phospholipid
cardiolipin​ is also found here )

Components of the Respiratory Chain are Contained in​ Four Large Protein Complexes ​Embedded in the Inner
Mitochondrial Membrane :

Electron flow
1​st​ NADH-Q oxidoreductase ​(Complex I ) - electrons are transferred from NADH t​o coenzyme Q​ (ubiquinone)
2​nd​ Q-cytochrome c oxidoreductase​ (Complex III) - which passes the electrons on to​ cytochrome c
3​rd​ cytochrome c oxidase​ (Complex IV) -​ completes the chain​, passing the electrons to O2 and causing it to be
reduced to H2O.

Some substrates with more positive redox potentials than NAD+/NADH​ pass electrons to Q ​( 2​nd​ ) via
a fourth complex, ​succinate-Q reductase​ (Complex II), rather than Complex I.

Flavoproteins​ - important components of Complexes​ I and II.

Ironsulfur proteins​ - found in Complexe​s I, II, and III.

The​ Q Cycle Couples Electron Transfer ​to Proton Transport in Complex​ III
- ​process is believed to involve:
cytochrome c1,
cytochrome bL,
cytochrome bH
Rieske Fe-S ​( (an unusual Fe-S in which one of the
Fe atoms is linked to ​two histidine​ residues rather than two cysteine residues )

Oxidative phosphorylation - ​flow of electrons through the ​respiratory chain​ generates ATP by this process.
 - The ​proton motive force ​caused by the electrochemical potential difference (negative on the matrix side)
drives the mechanism ​of ATP synthesis. ( The chemiosmotic theory )
- proton motive force drives a membrane-located​ ATP synthase​ that forms ATP in the presence of ​Pi + ADP.

Respiratory Control​ Ensures a Constant Supply of ATP -Most cells in the resting state are in​ state 4​, and respiration is
controlled by the availability of ADP.

Poisons​ inhibit the respiratory chain :

a. Barbiturates​ - inhibit electron transport via​ Complex I ​by blocking the transfer from Fe-S to Q.
b. Antimycin A & dimercaprol​ - inhibit the respiratory chain at C ​ omplex III.
c. H2S, carbon monoxide, and cyanide​ - classic poisons ; inhibit ​Complex IV ​and can therefore totally
arrest respiration.
d. Malonate​ - ​competitive inhibitor​ of Complex II.
e. Atractyloside​ - inhibits oxidative phosphorylation by​ inhibiting the transporter of ADP​ into and ATP
out of the mitochondrion.
f. Oligomycin​ - antibiotic; completely blocks oxidation and phosphorylation by blocking the flow of
protons through ​ATP synthase.
g. 2,4-dinitrophenol​ - most common​ uncoupler​; dissociate oxidation in the respiratory chain from
phosphorylation, causing respiration to become uncontrolled.
( ​Thermogenin ​(or the uncoupling protein) -​ physiological uncouple​r found in ​brown adipose tissue
that functions to generate body heat )

THE SELECTIVE PERMEABILITY OF THE INNER MITOCHONDRIAL MEMBRANE NECESSITATES EXCHANGE

TRANSPORTERS :
- Ionophores - ​Lipophilic molecule that permit Specific Cations to Penetrate Membranes
(Ex. ​valinomycin (K+) ​)

- Energy-linked transhydrogenase, -​protein in the inner mitochondrial membrane, couples the passage of
protons down the electrochemical gradient from outside to inside the mitochondrion.

- Oxidation of Extramitochondria​l NADH​ Is Mediated by Substrate Shuttles :

Glycerophosphate shuttle
Malate shuttle system

- ​Transport of ​High-Energy Phosphate from Mitochondria​ is facilitated by the​ Creatine Phosphate Shuttle

- ​Mitochondria maintain or accumulate cations such as K+, Na+, Ca2+, and Mg2+, and Pi.
( assumed that a primary proton pump drives cation exchange. )

CARBOHYDRATES OF PHYSIOLOGIC SIGNIFICANCE

Glucose ​- ​most important carbohydrate​; most dietary carbohydrate is absorbed into the bloodstream as glucose
formed by hydrolysis of dietary starch and disaccharides, and ​other sugars are converted to glucose ​in the
liver.
- ​major metabolic fuel​ of mammals (​except ruminants​) and a universal fuel of the fetus.

Glycobiology - ​study of the ​roles of sugars​ in health and disease.

Glycome​ - ​entire complemen​t of sugars of an organism, whether free or present in more complex molecules.
Glycomics -​ analogous term to genomics and proteomics, is the ​comprehensive study of glycomes, ​including genetic,
physiological, pathological, and other aspects.

CARBOHYDRATES ARE ​ALDEHYDE OR KETONE​ DERIVATIVES OF POLYHYDRIC ALCOHOLS

Classification of carbohydrates :
a. Monosaccharides​ - ​cannot be hydrolyzed ​into simpler carbohydrates. may be classified as trioses, tetroses,
pentoses, hexoses, or heptoses,depending upon the number of carbon atoms (3-7) and as aldoses or ketoses.

b. Disaccharide​ -​2 monosaccharide ​units ( Ex. lactose, maltose, isomaltose, sucrose, and trehalose. )
c. Oligosaccharides​ - condensation products of ​three to ten​ monosaccharides. Most are not digested by
human enzymes.

d. Polysaccharides​ - condensation products of ​more than 10 m ​ onosaccharide units. ( Ex. ​starches and
dextrins​ )
- In addition to starches and dextrins foods contain a wide variety of other polysaccharides that are
collectively known as​ nonstarch polysaccharide​s; they are not digested by human enzymes,
and are the ​major component of dietary fibe​r. (Ex​. cellulose ​from plant cell walls & ​inulin​, the
storage carbohydrate in some plants )

Sugars Exhibit Various Forms of Isomerism

Important types of isomerism found with glucose are as follows:

a. D and L isomerism ​- designation of a sugar isomer as the​ d form or its mirror image ​as the​ L form is
determined by its spatial relationship to the parent compound​ of the carbohydrates, the three-carbon sugar
glycerose.

b. Asymmetric​ carbon atoms also​ confers optical activity​ on the compound - rotates to the​ right
dextrorotatory (+) , ​to the ​left, levorotatory (−).

c. Pyranose and furanose ring structures ​- pyran (a​ six​-membered ring) or furan (a ​five ​membered ring)
glucose in solution,​ more than 99%​ is in th​e pyranose​ form.

d. Alpha and beta anomers

e. Epimers​ - Isomers differing as a result of variations in configuration of the —OH and —H on carbon
atoms 2,
3, and 4 of glucose are known as epimers.
f. Aldose-ketose isomerism
 Glycosides​- formed by condensation between the​ hydroxyl group of the anomeric carbon of a monosaccharide​, and a
second compound that may be another monosaccharide or, in the case of an ​aglycone, not a sugar.

Polysaccharides:
- ​Starch - ​homopolymer of glucose forming an α-glucosidic chain, called a glucosan or ​glucan​.
-the ​most important dietary carbohydrate​ in cereals, potatoes, legumes, and other vegetables.
- two main constituents are amylose & amylopectin

-​ Glycogen​ - is the​ storage ​polysaccharide in animals and is sometimes called animal starch.
- ​Inulin​ - polysaccharide of ​fructose​ (a fructosan) found in tubers and roots of dahlias, artichokes, and dandelions.
-readily soluble in water and is​ used to determine the glomerular filtration rate.

- Glycosaminoglycans (mucopolysaccharides) - ​are complex carbohydrates containing amino sugars and uronic
acids.
- ​Glycoproteins​ (also known as ​mucoproteins​) - protein containing branched or unbranched oligosaccharide chains
including fucose

Glycemic index​ measure of its digestibility, based on the extent to which it​ raises the blood concentration of glucose.
Glycophorin​ is a ​major integral membran​e glycoprotein of human ​erythrocytes.

THE CITRIC ACID CYCLE

The citric acid cycle​ (the Krebs or tricarboxylic acid cycle) - a sequence of reactions in mitochondria that oxidizes the
acetyl moiety of​ acetyl-CoA to CO2 ​&​ final common pathway​ for the oxidation of carbohydrate, lipid, and
protein because glucose, fatty acids, and most amino acids are metabolized​ to acetyl-CoA.

“ Acetyl CoA​ --> enters cycle by becoming ---> ​Citrate​---> oxidized ---> ​CO2 ​w/ the reduction of coenzymes --->
Reoxidation of coenzymes ​----> Phosphorylation of ADP to ​ATP”

​( in 1 turn of the cycle = ​9 ATP are generated ​via oxidative phosphorylation & ​1 ATP ​from the conversion of succinyl
CoA to succinate w/c = 10 )

“Initial reaction” ​= Acetyl CoA + Oxaloacetate =​ ​CITRATE!

​(​ citrate synthase​ )
Citrate​ ​is ​isomerized ​=​ isocitrate
( ​aconitase )

Isocitrate is dehydrogenated = oxalosuccinate ---eventually-->​ a-ketoglutarate

(​ isocitrate dehydrogenase​ )

a-ketoglutarate undergoes ​oxidative decraboxylation​ =​ Succinyl-CoA

( ​a-ketoglutarate dehydrogenase complex​ )

Succinyl-CoA converted to = ​succinate

( S​uccinate thiokinase / Succinyl-CoA synthase )

Succinate undergoes 1​st​ dehydrogenation reaction = ​fumarate

( ​succinate dehydrogenase ​)

Fumarate added w/ H20 =​ Malate

( ​Fumarase ​)

Malate is oxidized = ​Oxaloacetate!

( ​malate dehydrogenase ​)

1 mol​ of Acetyl-CoA =​ 3 mo​l of NADH &​ 1 mol ​FADH2 is produce ​per cycle

( 1 NADH = ​2.5 ATP​ , 1 FADH2=​ 1.5 ATP​ )

NADH 2.5 x 3 = 7.5 ATP

FADH2 1.5 x 1 = ​1.5 +
9

In addition,​ 1 ATP​ is formed by phosphorylation catalyzed by ​succinate

Thiokinase.

= so 9 + 1 = 10 ATP per turn of the citric acid cycle

4 of the B vit. Are essential in the TCA:

a. Riboflavin ( ​FAD ​) = cofactor of ​succinate dehydrogenase
b. Niacin ( ​NAD ​) = electron acceptor for isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, & malate
dehydrogenase
c. Thiamin/B1 ( ​thiamine diphosphate ​) = coenzyme for decarboxylation in the​ α-ketoglutarate dehydrogenase
reaction
d. Pantothenic acid ​= part of ​coenzyme A​, the cofactor esterified to “active” carboxylic acid residues: acetyl-CoA
and succinyl-CoA.

citric acid cycle is not only a pathway for oxidation,​ but is also a major pathway for interconversion of metabolites
arising from transamination and deamination of amino acids and providing the substrates for amino acid
synthesis by transamination.
 Oxaloacetate-------decarboxylation----->​ phosphoenolpyruvate
​( ​phosphoenolpyruvate carboxykinase​ ) =​ key enzyme​ that catalyzes net transfer out of the cycle into
gluconeogenesis.

Pyruvate ​------ carboxylation -------> Oxaloacetate ( “This rxn is ​impt in maintaining an adequate concentration
(pyruvate carboxylase) of oxaloacetate ​for the condensation reaction with acetyl-CoA”)

Lactate​ ( impt substrate for gluconeogenesis ) ---enters cycle via---> oxidation--->

Pyruvate--->--carboxylation--->oxaloacteate

Glutamate and glutamine​ ( impt. Anaplerotic substrates ) --- yields--> α-ketoglutarate

AMINOTRANSFERASE ​rxn example:

a. Alanine = pyruvate
b. Aspartate = oxaloacetate
c. Glutamate = a-ketoglutarate

Fatty acid synthesis:

Acetyl-CoA​, formed from​ pyruvate by the action of pyruvate dehydrogenase​ ,​ is the ​major substrate ​for long-chain
fatty acid synthesis in nonruminants.

fatty acid synthesis is a​ cytosolic pathway​; the mitochondrial membrane is​ impermeable​ to acetyl-CoA.

For acetyl-CoA to be available in the cytosol​, citrate is transported from the mitochondrion to the cytosol, then
cleavedi n a reaction catalyzed by​ citrate lyase.

Regulation of the Citric Acid Cycle Depends Primarily on ​a Supply of Oxidized Cofactors.

Hyperammonemia, -​ occurs in ​advanced liver disease​ and a number of (rare) genetic diseases of amino acid
metabolism, leads to loss of consciousness, coma and convulsions, and may be fatal.
- largely because of the ​withdrawal of α-ketoglutarate​ to form glutamate and then glutamine leading to
lowered concentrations of all citric acid cycle intermediates, and hence r​educed generation of
ATP​.

GLYCOLYSIS

Glycolysis​- p​rincipal route for carbohydrate metabolism​. The ability of glycolysis to provide ATP in the absence
of oxygen is especially important, because this​ allows skeletal muscle to perform​ at very high levels of work output
when oxygen supply is insufficient, and it allows tissues to survive anoxic episodes.

Glucose ---enters glycolysis by phosphorylation into -----> G6P

( ​HEXOKINASE ​) = uses ATP as phosphate donor

Liver cells also contain an isoenzyme of hexokinase, ​glucokinase.

Glucokinase = remove glucose from the hepatic portal blood​ following a meal, so regulating the concentration of
glucose available to peripheral tissues.

Under anaerobic conditions​, the ​NADH cannot be reoxidized​ through the respiratory chain, and pyruvate
is reduced to lactate catalyzed by lactate dehydrogenase.

Under aerobic conditions​, pyruvate is​ transported into mitochondria​ and undergoes
oxidative decarboxylation to acetyl-CoA then oxidation to CO2 in the citric acid cycle.
Pyruvate dehydrogenase​ complex - is ​analogous to the α-ketoglutarate​ dehydrogenase complex of the citric acid
cycle.
- ​Pyruvate​ is decarboxylated by the pyruvate dehydrogenase component of the enzyme complex to a
hydroxyethyl derivative of the thiazole ring of enzyme-bound ​thiamin
diphosphate​.
- The reaction is completed when the reduced lipoamide is reoxidized by a flavoprotein, dihydrolipoyl
dehydrogenase, ​containing FAD. ​Finally, the reduced flavoprotein is​ oxidized by
NAD+​, which in turn transfers reducing equivalents to the respiratory chain.
​( Pyruvate + NAD+ + CoA → Acetyl-CoA + NADH + H+ + CO2 )

Inhibition of Pyruvate​ Metabolism Leads to​ “Lactic Acidosis”

Ex - Arsenite and mercuric ions =​ inhibit pyruvate dehydrogenase, as does a dietary deficiency of thiamin allowing
pyruvate to accumulate.

Metabolism of Glycogen

Glycogen = ​the​ major storage carbohydrate​ in animals, corresponding to starch in plants; it is a branched polymer of
α-d-glucose.
= ​occurs mainly in​ liver ​and ​muscle​, with modest amounts in the brain.
= Muscle glycogen provides a ​readily available source of glucose-1-phosphate​ for glycolysis within the muscle
itself.
= Liver glycogen functions as a​ reserve to maintain the blood glucose concentration​ in the fasting state.

Glycogenesis ​occurs mainly in muscle & liver.

Glycogenin​ - protein involved in the​ initial steps of glycogen synthesis.
Glycogen synthase - ​catalyzes the formation of a glycoside bond between C-1 of the glucose of ​UDPGlc​ and C-4 of a
terminal glucose residue of glycogen, ​liberating uridine diphosphate (UDP).

Glycogen phosphorylase-​ catalyzes the​ “rate-limiting step” in glycogenolysis.

Lysosomes ​- can engulf glycogen granules where acid maltase catalyzes the hydrolysis of glycogen to
glucose.
(
use diagram for guide )
cAMP​ =activates glycogen phosphorylase
Protein Phosphatase-1 =​Inactivates Glycogen Phosphorylase
Epinephrine​ and ​norepinephrine = ​stimulates α1 adrenergic receptors of the liver and there will be
cAMP-independent activation of glycogenolysis.
Gluconeogenesis & the Control of Blood Glucose
Explain the importance of gluconeogenesis in glucose homeostasis.
■ Describe the pathway of gluconeogenesis, how irreversible enzymes of
glycolysis are bypassed, and how glycolysis and gluconeogenesis are regulated
reciprocally.
■ Explain how plasma glucose concentration is maintained within narrow limits
in the fed and fasting states.

Gluconeogenesis - ​process of synthesizing glucose or glycogen from ​noncarbohydrate precursors.

Liver and kidney - ​are the ​major gluconeogenic tissues​; the kidney may contribute up to​ 40%
of total glucose synthesis in the fasting state and more in starvation.

( Failure of gluconeogenesis is usually fatal, ​Hypoglycemia ​causes brain dysfunction, which can lead to coma and death.
Glucose is also important in maintaining adequate concentrations of intermediates of the citric acid cycle )

Pyruvate carboxylase -​ catalyzes the carboxylation of​ pyruvate to oxaloacetate​, an ATP-requiring reaction in which the
vitamin​ biotin is the coenzyme.

phosphoenolpyruvate carboxykinase - ​catalyzes the decarboxylation and phosphorylation of oxaloacetate to

phosphoenolpyruvate​ using GTP as the phosphate donor.

Fructose 1,6-bisphosphatase -​ Its presence ​determines ​whether a tissue i​s capable of synthesizing​ glucose
(or glycogen) not only from pyruvate, but also from triose phosphates.

Glucagon​ and​ epinephrine ​- ​inhibit glycolysis ​and stimulate gluconeogenesis in the liver by​ increasing ​the
concentration of cAMP.
- This in turn ​activates cAMP-dependent protein kinas​e, leading to the phosphorylation and ​inactivation​ of
pyruvate kinase.
- responsive to a​ decrease in blood glucose.

Phosphofructokinase (phosphofructokinase-1) - key​ position in ​regulating glycolysis​ and is also subject to feedback
control.
 - inhibited by citrate and by normal intracellular concentrations of ATP and is activated by 5′
AMP.

fructose 2,6-bisphosphate - most potent​ positive allosteric activator of phosphofructokinase- 1 and inhibitor of
fructose 1,6-bisphosphatase in liver.

(Please do understand the diagram for the cori cycle )

( impt to remember: GLUT1, GLUT4 & SGLT1 )

Glucosuria​ Occurs When the Renal Threshold for Glucose Is Exceeded.

Diabetes mellitus​ type 1 (insulin-dependent diabetesmellitus;​ IDDM​) - is characterized by decreased glucose
toleranceas a result of d​ecreased secretion of insulin​ because
ofprogressive destruction of pancreatic β-islet cells.

Diabetes mellitus type 2​ (noninsulin-dependent diabetes, ​NIDDM​) - as a result of ​impaired sensitivity​ of tissues to
insulin action.

( PLEASE REFER TO THE SUMMARY SECTION FOR MORE INFORMATION THAT HAVE BEEN SKIPPED OR IF LACKING
THANK YOU)