Glycolysis to ATP synthesis

Activated Carrier Molecules

Molecules that transport energy from energetically favorable reaction to unfavorable reaction (ATP,NADH, FADH2)

ATP (Adenosine Triphosphate)

Most widely used activated carrier molecule, hydrolisis makes ADP, which liberates phosphate to use as energy

NADH -—> NAD+, FADH2 —> FAD+

Carrier molecule that participates in Oxidation reduction reaction, carries H+ and electrons

Nucleotide Functions

Carry chemical energy, form coenzymes, specific signaling molecules

Carbohydrate Metabolism

Starches are broken down into oligosacharides, which are hydrolyzed into glucose by alpha glucosidase.

sucrose is broken down to glucose and fructose by sucrase

SGLT

sodium glucose co-transporter : gut to intestinal cells

GLUT2 glucose transporter 2

Low affinity, high Km

from intestinal cells into blodd

liver pancreatic beta cells, certain neurons

Enable sense to sense and response to extracellular glucose

GLUT 1/3 glucose transporter

High affinity, low km,’

High Transport

glut1: everywher except neurons

Glut3: neurons

Glut4 glucose transporter

High affinity

Insulin sensitive gluose transporte on skeletal muscle, adipocytes

impaired during diabetes due to insulin resistance

activated during excersice independently of insuline

Glut 5

fructose transporter

Glycolysis

break down of glucose to pyruvate energy obtain

Glycolysis Stage 1

Use of Energy Glucose to F-1,6-BP

Glucose + ATP → hexokinase → Glucose 6 - Phosphate

Commited step

irriversible reaction

allosterically inhibited by glucose -6 phosphate

traps glucos in the cells

Hexokinase (HK)

4 major iso form of mammalian HK

HK 1-3 km « 1mM (high Affinity)

HK 4 = glucokinase low affinity. Hk 4 found in liver

HK 4 or glucokinase is not subject to end product inhibition, mutation is linked to diabetes

glucose-6-phosphate → phosphoglucose isomerase <--- Fructose 6 phosphate

Reversible

formation of fructose 6 phosphate

rearrangement of chemical to by isomerase to form another

Phosphofructokinase reaction (PFK-1) (rate limiting Enzyme)

Fructose 6-phosphate + ATP →

→ fructose 1,6 biphosphate

Irreversible

Energy consumptio

PFK1: allosteric enzyme that regulates the pace of glycoslisis principal rate limiting enzyme

Inhibited by ATP activated bt AMP

Allosterically activated by fructose 26 biphosphate

Glycolysis: Stage 2

No energy used or extracted

two 3-carbon fragments are produced from one 6 carbon sugar

Cleavage of 6 carbon sugar

fructose 1,6 biphosphate → aldolase A <- dihidroxyacetone + glyceraldehyde 3- phosphate

fructose → fructokinase → fructose 1-p → aldolase B <- DHAP + glyceraldehyde

depending on sugar the reaction is different

Dihydroxyacetone phosphate → triose phosphate isomerase <- glyceraldehyde 3 - phosphate

salvage of three carbon fragment

Glycolysis stage 3

Energy extracted

2× 2 atp / molecule of glucose

the oxidation of three carbon fragments yields atp

How enzymes couple oxidation to energy storage

Glyceraldehyde -3 phosphate dehydrogenase, and phosphoglycerate kynase

oxidation of glyceraldehyde 3- phosphate, the reaction gives a NADH and 1,3 biphosphoglycerate

the kynase removes the phosphate group from 1,3 biphosphoglycerate and generates 1 atp and 3 - phosphoglycerate

3 -phosphoglycerate → phosphoglycerate mutase <- 2 -phosphoglycerate

reversible rearrangfe phosophate group

2 -phosphoglycerate -—> enolase <- phosphoenolpyruvate

enol is oh bonded to c=c, the removal of H2O creates a high energy enol phosphate linkage

phosphoenol pyruvate + ADP + H → pyruvate kinase → pyruvate + ATP

irreversible

ATP formation

Pk is inhibited by ATP

Glycolysis Energy generation

4 ATP generated - 2 ATP use: total 2 ATP / Glucose

2NADH molecules generated

NAD regeneration in anaerobic conditions

Fermentation leads to excretion of lactate,which is self limiting

Glycolysis overview

6-c sugar to two pyruvate molecules

2ATP net production

2NADH

Rate of glycolysis is adjusted to meet the cells need for ATP

3 allosteric controlled enzymes: hexokinase, PFK-1, Pyruvate Kinase

These 3 enzymes catalyze reaction with large negative dG regulate the entire pathway