Glucose Catabolism - Glycolysis and Pentose Phosphate Pathway

significance of glycolysis

-all human cell types can generate ATP from glucose

-glycolysis generates ATP in presence or absence of O2

-glucose is major fuel for brain and is required by erythrocytes

-connects with TCA Cycle through reactions of pyruvate dehydrogenase complex

stages 1 and 2 of glycolysis

stage 1: glucose is converted into two molecules of glyceraldehyde-3-phosphate (GAP) using two ATP molecules (energy investment phase)

stage 2: two molecules of GAP are converted to pyruvate, with generation of four ATP molecules (payoff phase)

what is generated in phases 1 and 2 of glycolysis

phase 1: two ATP consumed

phase 2: four ATP generated (net 2 ATP/glucose), two NADH, two pyruvate for further oxidation through TCA Cycle

how is glucose-6-phosphate (G6P) a branch point in carbohydrate metabolism

-phosphorylation traps glucose within cell as G6P

-reaction carried out by hexokinase or glucokinase

-G6P may proceed through pentose phosphate pathway or glycogen synthesis and can be generated by glycogen breakdown or gluconeogenesis (overall it is used in multiple pathways)

three fates of pyruvate 

1. can be used aerobically where it is made through glycolysis then goes through TCA Cycle generating ATP

2. can be used anaerobically though homolactic fermentation to generate lactate or alcoholic fermentation to generate ethanol 

Note: during glycolysis NADH is generated and through TCA and fermentation NADH gets converted back to NAD+

compare amount of ATP produced from fermentation and oxidative phosphorylation

fermentation produces 2 ATP where’s OXPHOS produces as much as 32 ATP from glucose

why is rate of ATP production by glycolysis much faster than by oxidative phosphorylation

glycolysis is faster because it is more simple and doesn’t have membrane transport, electron transfer steps, proton gradients and oxygen dependence

which enzyme is the major regulatory point for glycolysis and why

also how is it activated and inhibited

phosphofructokinase-1 because it catalyzes an irreversible step committing glucose to further breakdown and energy production

activated by AMP and fructose-2,6-bisphosphate

inhibited by ATP and citrate

Ex: as ATP levels drop during exercise AMP rises to activate phosphofructokinase to generate more ATP

galactose

obtained from hydrolysis of disaccharide lactose

mannose

found in polysaccharides and glycoproteins

fructose

-converted to F1P in liver, bypassing metabolic control (phosphofructokinase)

-this means that fructose is less controlled during metabolism, which can lead to rapid conversion of pyruvate

-high levels may deplete ATP, increasing lipogenesis and uric acid levels (bad to consume as lipogenesis is converting it to fat leading to fatty liver disease)

what is the purpose of the pentose phosphate pathway

catabolic pathway of glucose metabolism to generate essential molecules: those essential molecules are NADPH for reductive biosynthesis and Ribose-5-phosphate for nucleotide biosynthesis

main location for pentose phosphate pathway

liver due to its involvement in fatty acid biosynthesis

what is the substrate for pentose phosphate pathway 

G6P, which may come from hexokinase and glucokinase action on glucose, by glycogen breakdown or through glujconeogenesis 

what is generated from pentose phosphate pathway

two molecules of NADPH and one R5P generated per each G6P

what is the control point of pentose phosphate pathway

glucose-6-phosphate dehydrogenase (G6PD) because it catalyzes rate-limiting step, which generates NADPH

how is NADPH made from PPP connected to glutathione

-glutathione protects cells from oxidative damage

-when glutathione neutralizes it becomes oxidative glutathione (GSSG) as it neutralizes harmful peroxides, converting to water and alcohol

-too much buildup not good and can generate reactive oxygen species that damage membranes, proteins, and DNA 

-to convert GSSG back to active form it needs NADPH to be reduce back to 2GSH

summary of molecules to know: hexokinase, glucokinase, phosphofructokinase 1, glucose-6-phosphate dehydrogenase, glutathione peroxidase 

• Hexokinase – Ubiquitous enzyme that phosphorylates glucose to G6P with high affinity and is inhibited by G6P.

• Glucokinase – Liver and β-cell isoform of hexokinase with low affinity and no G6P inhibition, acting as a glucose sensor.

• Phosphofructokinase-1 (PFK-1) – Rate-limiting enzyme of glycolysis that converts F6P to F1,6BP and is tightly regulated by ATP, AMP, and F2,6BP.

• Glucose-6-phosphate dehydrogenase (G6PD) – First and rate-limiting enzyme of the oxidative pentose phosphate pathway that generates NADPH.

• Glutathione peroxidase – Antioxidant enzyme that uses reduced glutathione (GSH) to detoxify hydrogen peroxide into water.

summary of terms to know: ATP/ADP/AMP, NAD+/NADH, NADP+/NADPH, glucose, galactose, mannose, fructose, G6P, pyruvate, lactate, citrate, R5P, glutathione

• ATP – Primary cellular energy currency.

• ADP – Lower-energy ATP precursor regenerated during ATP use.

• AMP – Sensitive indicator of low cellular energy.

• NAD⁺/NADH – Redox pair used mainly for catabolic energy production (ETC).

• NADP⁺/NADPH – Redox pair used mainly for biosynthesis and antioxidant defense.

• Glucose – Main blood sugar and universal fuel molecule.

• Galactose – Milk sugar component converted to glucose in the liver.

• Mannose – Hexose used largely in glycoprotein synthesis.

• Fructose – Dietary sugar metabolized primarily in the liver via fructolysis.

• Glucose-6-phosphate – Key metabolic branchpoint directing glucose into glycolysis, glycogenesis, or PPP.

• Pyruvate – End product of glycolysis and major metabolic crossroads.

• Lactate – Reduced form of pyruvate used to regenerate NAD⁺ during anaerobic glycolysis.

• Citrate – TCA cycle intermediate that signals high energy and inhibits PFK-1.

• Ribose-5-phosphate – PPP product used for nucleotide synthesis.

• Glutathione (GSH) – Major cellular antioxidant that detoxifies reactive oxygen species.

what are anabolic processes and examples

definition- larger molecules synthesized from simpler components, energy input required

biosynthetic and fuel storage pathways

what are catabolic processes

large-complex molecules converted into smaller metabolites

conversion of metabolic fuels into energy to power metabolic processes

three phases of energy transformation in cells

1. fuel oxidation

2. conversion of energy from fuel into ATP

3. use ATP to enable processes requiring energy

what is cellular respiration and its phases 

definition- uses energy from fuels, usually together with O2, to make ATP

phase 1: fuels oxidized and electrons transferred to cofactors

phase 2: cofactors are oxidized and ATP is synthesized 

ATP is a high-energy molecule due to its what

phosphoanhydride bonds

structural basis of high phosphoryl transfer potential of ATP

electrostatic repulsion- released electrostatic repulsion as two negative oxygens are separated lowering energy in products compared to reactants

resonance- more resonance in products (blue and pink arrows can happen at same time)

is electron transfer from metabolic intermediates to O2 direct? 

no, substrates transfer electrons to special carriers, which are either pyridine nucleotides or flavones 

characteristics of NAD(P)+ and NAD(P)H

made from niacin (vitamin B3)

two electron acceptors

O2 can only accept electrons 1 at a time

characteristics of FAD and FADH2

flavins must be obtained in diet as riboflavin (vitamin B2)

can accept 1 or 2 electrons

summary of terms: phosphocreatine, Acetyl CoA, riboflavin, niacin

• Phosphocreatine – Rapid-release energy buffer that donates phosphate to regenerate ATP in muscle.

• Acetyl-CoA (assuming this is what you meant by “acetylcholine CoA”) – Central metabolic intermediate that carries two-carbon units into the TCA cycle.

• Riboflavin (Vitamin B₂) – Precursor of FAD/FMN used in redox reactions.

• Niacin (Vitamin B₃) – Precursor of NAD⁺/NADP⁺ essential for metabolic redox reactions.