NOTES

NOTES
CARBOHYDRATE METABOLISM

CITRIC ACID CYCLE

(KREBS CYCLE)
osms.it/citric-acid-cycle
▪ Generates energy in the form of GTP, MNEMONIC: T-rex Loves
NADH, and FADH2 and Cares For Nachos
▪ Occurs in mitochondria Five required cofactors
▪ Starts with acetyl-CoA → CO2 Thiamine
Lipoic acid
Process
CoA
▪ Acetyl-CoA + oxaloacetate (via citrate
FAD+
synthase) → citrate + CoA
NAD+
▪ Citrate (via aconitase) → isocitrate
▪ Isocitrate + NAD+ (via isocitrate
dehydrogenase) → α-ketoglutarate +
NADH + CO2
▫ Rate-limiting step
▪ α-ketoglutarate + NAD+ + CoA-SH
(α-ketoglutarate dehydrogenase) →
succinyl-CoA + NADH + CO2
▫ Requires five cofactors: thiamine, lipoic
acid, CoA, FAD+, NAD+
▫ See mnemonic
▪ Succinyl-CoA + phosphate + GDP (via
succinate thiokinase) → succinate + GTP
▪ Succinate + FAD+ (via succinate
dehydrogenase) → fumarate + FADH2 Figure 1.1 Mnemonic for the five cofactors
required by α-ketoglutarate dehydrogenase.
▪ Fumarate + H2O (via fumarase) → malate
▪ Malate + NAD+ (via malate dehydrogenase)
→ oxaloacetate + NADH
▫ Oxaloacetate then enters next cycle
▪ Generates one GTP molecule, three NADH
molecules, one FADH2 molecule

OSMOSIS.ORG 1
 Figure 1.2 The citric acid (Krebs) cycle. Each acetyl-CoA molecule generates 12 ATP.

ELECTRON TRANSPORT CHAIN &

OXIDATIVE PHOSPHORYLATION
osms.it/etc-and-oxidative-phosphorylation
Oxidative phosphorylation
▪ Generates energy as ATP
▪ Occurs in inner mitochondrial membrane
Electron transport chain
▪ Series of proteins, lipids, metals that
facilitates electron movement → proton
gradient used to create ATP
▪ Starts with electron donors NADH, FADH2
▫ NADH from cytoplasm comes through
malate-aspartate shuttle
▫ FADH2 from cytoplasm comes through
glycerol-3-phosphate shuttle
▫ NADH donates electron to complex I
(contains flavin mononucleotide, iron-
sulfur centers) → NAD+
▫ FADH2 donates electron to complex II
(i.e. succinate dehydrogenase) → FAD
▫ Electrons from either complex flow into
coenzyme Q (ubiquinone)
▫ Coenzyme Q passes electrons to
cytochromes (proteins with heme

2 OSMOSIS.ORG

groups — Fe3+ + e- ↔ Fe2+): complex III
(cytochromes b and c1) → cytochrome
c → complex IV (cytochrome oxidase:
cytochromes a, a3) → oxygen
▪ Movement of electrons → electrical current
→ complexes I, III, IV use this energy to
pump protons across inner mitochondrial
membrane
Figure 1.3 The flow of electrons through the electron transport chain, which takes place in the
inner mitochondrial membrane.
Chapter 1 Biochemistry: Carbohydrate Metabolism
▪ Protons can move back into mitochondria
through F0 → proton gradient forms,
powering F1: ADP → ATP
▫ Collectively called complex V
▪ An ADP/ATP antiport pumps ATP into
cytoplasm of the cell, supplies complex V
with new ADP
OSMOSIS.ORG 3
 Figure 1.4 Oxidative phosphorylation. The passing of electrons along the electron transport
chain generates an electrical current, which provides the energy that allows complexes I, III, and
IV to pump protons into the space between the inner and outer mitochondrial membranes. This
creates a gradient across the inner mitochondrial membrane. The protons use proton channel F0
to flow down the gradient, back into the mitochondrial matrix. F0 is attached to enzyme F1, an
ATP synthase, which uses the proton gradient to phosphorylate ADP → ATP.

GLUCONEOGENESIS
osms.it/gluconeogenesis
▪ Synthesis of glucose from non-
carbohydrate substrates
▫ E.g. amino acids, lactate, glycerol
▪ Occurs primarily in liver cells; also in
epithelial cells of kidney, intestine
▫ Inside cytoplasm, mitochondria,
endoplasmic reticulum
▪ Starts with glycogenolysis after glucose
depletion
Process
▪ Like backwards glycolysis, with three
exceptions
▪ Obtaining pyruvate
▫ Lactate (via lactate dehydrogenase) →
pyruvate
▫ Amino acids (not leucine, lysine); e.g.
alanine (via alanine transaminase) →
pyruvate
▪ Obtaining ATP, glycerol
▫ Triacylglyceride breakdown → fatty
acids and glycerol → acetyl CoA + ATP
(β-oxidation)
▪ Pyruvate (via pyruvate carboxylase) →
oxaloacetate
▪ Oxaloacetate (malate dehydrogenase) →
malate
▪ Malate leaves mitochondria; malate (via
malate dehydrogenase) → oxaloacetate
▪ Oxaloacetate (via PEPCK) →
phosphoenolpyruvate (PEP)
▪ PEP undergoes reversed glycolysis
reactions until dihydroacetone-phosphate
(DHAP)
▫ Alternatively, glycerol (via glycerol
kinase) → glycerol-3-phosphate;

4 OSMOSIS.ORG
 Chapter 1 Biochemistry: Carbohydrate Metabolism

glycerol-3-phosphate (via glycerol-3- ▪ Fructose-6-phosphate (via isomerase) →

phosphate dehydrogenase) → DHAP glucose-6-phosphate
▪ DHAP (via aldolase) → fructose-1,6- ▪ Glucose-6-phosphate (via glucose-6-
bisphosphate phosphatase) → glucose
▪ Fructose-1,6-bisphosphatase → fructose-
6-phosphate
▫ Rate-limiting step

Figure 1.5 The process of gluconeogenesis.

OSMOSIS.ORG 5
 GLYCOGEN METABOLISM
osms.it/glycogen-metabolism
▪ Polymer of glucose molecules linked by
glycosidic bonds
▪ Stores energy in skeletal muscle, liver
Glycogen synthesis
▪ Glucose + phosphate (via hexokinase) →
glucose-6 phosphate
▪ Glucose-6 phosphate (via
phosphoglucomutase) → glucose-1-
phosphate + energy (UTP)
▪ Glucose-1-phosphate + UTP (via UDP-
glucose pyrophosphorylase) → UDP-
glucose
▪ UDP-glucose added (via glycogen
synthase) to glycogen branch/glycogenin
(→ alpha-1,4-glycosidic bond)
▪ Branching enzyme cuts off part of glucose
chain, creates branch (→ alpha-1,6-
glycosidic bond)
Glycogen breakdown, AKA glycogenolysis
▪ Glucagon → liver breakdown of glycogen
▪ Epinephrine → skeletal muscle breakdown
of glycogen
▪ Glycogen phosphorylase cleaves alpha-1,4
bonds on branches; catalyzes phosphate
transfer to glucose residue → one glucose-
1-phosphate is released at a time
▫ Repeats until branch is only 4 glucose
units long
▪ Debranching enzyme: 4-alpha-
glucanotransferase moves 3 glucose units
off branch, onto main chain; alpha-1,6-
glucosidase cleaves last remaining glucose
6 OSMOSIS.ORG
▪ Cleaved glucose-1-phosphate (via
phosphoglucomutase) → glucose-6-
phosphate
▫ With glucose-6-phosphate
▪ In liver cells, glucose-6-phosphatase
removes phosphate → free glucose into
blood
▪ In skeletal muscle, glucose-6-phosphate →
glycolysis pathway
Regulation
▪ Principles
▫ Glycogen synthase: active without
phosphate
▫ Glycogen phosphorylase: active with
phosphate
▪ Hormones
▫ Insulin: binds to membrane tyrosine
kinase receptors → protein phosphatase
removes phosphates → glycogen
synthase activates, glycogen
phosphorylase deactivates
▫ Glucagon: binds to membrane G-protein
coupled receptors (in liver) → ATP
(adenylyl cyclase) → cAMP → kinase
A → adds phosphates → glycogen
phosphorylase activates, glycogen
synthase deactivates
 Chapter 1 Biochemistry: Carbohydrate Metabolism

Figure 1.6 The process of glycogen synthesis.

OSMOSIS.ORG 7
 Figure 1.7 Glycogen breakdown. The process is completed differently in the liver and skeletal
muscles due to the respective presence and absence of glucose-6-phosphatase in each.

8 OSMOSIS.ORG
 Chapter 1 Biochemistry: Carbohydrate Metabolism

Figure 1.8 The role of insulin in the regulation Figure 1.9 The role of glucagon in the
of glycogen levels. regulation of glycogen levels.

GLYCOLYSIS
osms.it/glycolysis
▪ Energy-producing breakdown of glucose glucose-6-phosphate
into pyruvate ▫ Uses one ATP molecule
▪ Occurs in cytoplasm of all cells ▪ Glucose-6-phosphate (via
phosphoglucoisomerase) → fructose-6-
PROCESS phosphate
▪ Glucose transporter (GLUT) carries glucose ▪ Fructose-6-phosphate (via
into cell phosphofructokinase-1) → fructose-1,6-
bisphosphate
▪ Kinases (hexokinase, glucokinase)
phosphorylate glucose → conformational ▫ Rate-limiting step
change, i.e. glucose can’t diffuse out) → ▫ Uses one ATP molecule

OSMOSIS.ORG 9
 Enzyme activation
▪ Fructose-6-phosphate (via
phosphofructokinase-2) → fructose-2,6-
bisphosphate
▫ Up-regulated by insulin; down-
regulated by glucagon
▫ Fructose-2,6-bisphosphate activates
phosphofructokinase-1
▪ Fructose-1,6-bisphosphate (via aldolase)
→ glyceraldehyde 3-phosphate (G3P) +
dihydroacetone-phosphate (DHAP)
▫ DHAP (via isomerase) → G3P → 2x
G3P molecules per glucose
▪ G3P (via G3P-dehydrogenase) →
1,3-diphosphoglycerate (1,3-BPG); H+ +
NAD+ → NADH (x2)
▫ 2x NADH enter electron transport chain
▪ 1,3-BPG + ADP (via phosphoglycerate
kinase) → 3-phosphoglycerate + ATP (x2)
▫ Creates two ATP molecules
PENTOSE PHOSPHATE PATHWAY
osms.it/pentose-phosphate-pathway
▪ Synthesis of ribose, NADPH from unused
glucose
▪ Occurs in cytoplasm of all cells
Irreversible oxidative phase
▪ Glucose-6-phosphate + NADP+ (via
glucose-6-phosphate dehydrogenase) →
6-phosphogluconate + NADPH
▫ Rate-limiting step
▪ 6-phosphogluconate + NADP+
(6-phosphogluconate dehydrogenase) →
ribulose-5-phosphate + NADPH + CO2
10 OSMOSIS.ORG
▪ 3-phosphoglycerate (via mutase) →
2-phosphoglycerate (x2)
▪ 2-phosphoglycerate (via enolase) →
phosphoenolpyruvate (PEP) + H2O (x2)
▪ PEP + ADP (via pyruvate kinase) →
pyruvate + ATP (x2)
▫ Creates two ATP molecules
▫ Up-regulated by fructose-1,6-
bisphosphate (feed-forward regulation)
▫ Down-regulated by ATP, alanine
▪ In total, process generates two ATP
molecules
▪ In cells with oxygen, pyruvate enters citric
acid cycle, electron transport chain to make
more ATP
▫ 30–32 in total
Reversible non-oxidative phase
▪ Two options:
▫ Ribulose-5-phosphate (via isomerase)
→ ribose-5-phosphate
▫ Ribulose-5-phosphate (via epimerase)
→ xylulose-5-phosphate
 Chapter 1 Biochemistry: Carbohydrate Metabolism

Figure 1.10 Glycolysis.

OSMOSIS.ORG 11
 Figure 1.11 Pentose phosphate pathway.

12 OSMOSIS.ORG