GLYCOLYSIS / EMBDEN MEYERHOF PATHWAY

o
Malate-Aspartate Shuttle
Major pathway for glucose metabolism in all cells, nearly universal
CYTOSOL
MITOCHONDRIA
In cytosol, non-compartmentalized, primitive
OAA ASP ASP OAA
Sets the stage for complete oxidation of glucose into CO2 and H2O (via TCA: pyruvic acid to acetyl CoA)
NADH NAD
NAD NADH ETC
Integrated into many other metabolic processes, with intermediates common to other pathways
Mal Mal
3 Types of Chemical Transformations
o
-glycerophosphate Shuttle
o
Degradation of carbon skeleton of glucose to yield pyruvate
CYTOSOL
MITOCHONDRIA
o
Phosphorylation of ADP to ATP by high energy PO4 compounds
DHAP DHAP
o
Transfer of H+ atoms or electrons to NAD NADH+H
NADH NAD
FAD FADH ETC
Glycolytic intermediates are phosphorylated
-GP -GP
o
PO4 negative charge at ph 7 traps intermediate in the cell

Energetics
o
PO4 groups essential for enzymatic conservation of energy

Aerobic: G + 2 Pi + 2 ADP 2 lactate + 2 ATP + 2 H2O;

o
PO4 binds to active site of enzymes providing binding energy to lower activation energy
o
net of 2 ATP / G; @ oxygen debt or lacking mitochondria, no net NADH+H consumption
Property
Hexokinase
Glucokinase

Anaerobic: G+ 2Pi + 2 NAD + 2 ADP 2 pyruvate + 2 ATP + NADH + 2H+ + H2O;

Tissue Distribution
Most tissues
Liver, pancreas
o
net of 2 ATP / G; 2 NADH+H / G, NADH into ETC = 2 or3 ATP
Glucose Km
Low (0.1mM)
High (10mM)
Reaction
Moles ATP produced or consumed / mole G
Vmax
Low
High
G G6P
-1
Substrate specificity
D-glucose, hexoses
D-glucose only
F6P F1,6BP
-1
Inhibition by G6P
yes
no
GA3P 1,3BPG
+4/+6
Insulin induction
no
yes
1,3BPG 3-PG
+2
Shuttle System: NADH+H not used in pyr reduction to lac transported across mitochondrial membrane
PEP

Pyr
+2
Reduction of organic molecule by NADH+H go to mito reoxidation with NAD in mito back to cytosol
+2 (+6/+8 if aerobic)
Net
Step

PAY OFF STAGE

PREPARTORY STAGE

Phosphorylation

Substrate
Glucose
(G)

Product
Glucose-6-phosphate (G6P)

Enzyme
Hexokinase,
glucokinase
Phosphoglucose
isomerase

Action
Effectively traps G
inside the cell
Aldose PO4
ketose PO4

Stimulators / Activators

Allosterically by F6P,
AMP, ADP and F2,6BP

Inhibitors / Deactivators
2-deoxyglucose

Notes
Irreversible, 1st regulatory step, requires ATP with
Mg2+

Isomerization

G6P

Fructose-6-phosphate (F6P)

Phosphorylation

F6P

Fructose-1,6-bisphosphate
(F1,6BP)

Phosphofructokinase-I

Adds another PO4

group

Cleavage

F1,6BP

Glyceraldehyde-3-phosphate
(GA3P) dihydroxyacetone
phosphate (DHAP)

aldolase

Forms 2 triose
phosphates

Reversible

Isomerization

DHAP

GA3P

Phosphotriose
isomerase

Converts DHAP to
GA3P

Reversible

Reduces GA3P

1st redox, requires NAD from NADH from pyruvate to

lactate, maybe linked to ETC if aerobic, 2,3-BPG in
RBC (Rapoport-Luebering Shunt) for O2 transfer by
mutase

Oxidation

GA3P

1,3-bisphosphoglyceric acid
(1,3BPG)

GA3P dehydrogenase
(DH)

Formation

1,3BPG,
ADP

ATP, 3-phosphoglycerate
(3PG)

Phosphoglycerate
kinase

Isomerization

3PG

2-phosphoglycerate (2PG)

Dehydration

2PG

Phophoenolpyruvate (PEP)

Phosphoglycerate
mutase
Enolase (Mg2+ at
active site)

Formation

PEP

Pyruvate (Pyr)

Pyruvate kinase

Reduction

Pyr

Lactate (Lac)

Lactic acid DH (LDH1:

heart, to lactate; LDH2:
skel musc, to pyruvate)

Reversible

Arsenate, iodoacetate

Transfers high energy

group from 1,3BPG +
ADP
Shifts PO4 from C3 to
C2
Yields high energy
compound
Produces 2ATP via
Substrate level
phosphorylation

ATP, citrate, long chain fatty acids

(LCFA)

Irreversible, 2nd regulatory step, committed step,

requires ATP, PFK-II reserves excess F6P as F2,6P
for PFK-I

Reversible, substrate level phosphorylation,

produces 2 moles ATP / mole glucose

Allosterically by F-1,6BP, insulin stimulates

pyr kinase

Fluoride (binds with Mg2+)

Reversible

ATP, acetyl CoA, LCFA, covalent

modification of pyr kinase,
glucagon inhibits pyr kinase via
cAMP dependent phosphorylation

Irreversible, 3rd regulatory step

Reversible, lactic acid fermentation, anaerobic part
of EMP, major fate of Pyr in skel musc and RBC,
involves reoxidation of NADH, ensures NAD supply

TRICARBOXYLIC ACID CYCLE / KREBS CYCLE / CITRIC ACID CYCLE

ensures complete oxidation of glucose to CO2 and H2O

in mitosol, amphibolic
provides intermediates for biosynthesis of other compounds
final oxidative pathway for CHO, FA, AA
oxidation of molecules accounts for greatest fraction(2/3) of O2 consumption and ATP production
principal source of reducing equivalents that enter ETC
Energetics: acetyl CoA + 3NAD + FAD + GDP + Pi + H2O 2CO2 + 3NADH + 3H+ + FADH2 + GTP + CoASH
Reactions
Moles ATP / Mole Pyr
Moles ATP / Mole G
3 (NADH)
6
Pyr aCoA
3 (NADH)
6
Ict oxalosuccinate / KG
3 (NADH)
6
KG sCoA
1 (ATP)
2
sCoA suc
2 (FADH2)
4
Suc fum
3 (NADH)
6
Mal OAA
15
30 (+6/+8 from aerobic glycolysis)
Total

Preliminary Oxidation

Step
Oxidation
(3 Steps)
Decarboxylation
Oxidation /
Transfer
Oxidation /
Reoxidation
Condensation

TCA Cycle

Isomerization

Substrate

Product

Anaplerotic Reactions: refill / replenish depleted intermediates in TCA which have been used for biosynthetic
reactions; continuous functioning
o
Carboxylation of pyruvate

Principal anaplerotic reaction, in mitochondria

Catalyzed by pyruvate carboxylase, ATP-dependent, allosterically activated by aCoA and LCF

acylCoA
o
Reductive carboxylation of pyruvate to malate

In cytosol

Catalyzed by NADPH-linked malate enzyme (NOT identical to mitochondrial malate DH)

Provides NADPH for FA synthesis

o
Transamination of aspartic acid to OAA
o
Transamination of glutamic acid to KG
o
Degradation of C skeletons of glucogenic AAs

Met, Val, Ile sCoA

Tyr, Phe Fum

pyruvate

Acetyl CoA

pyruvate
Hydroxyethyl derivative /
Acetyl group as thioester
in lipoic acid
Sulfhydryl lipoic acid /
FADH2
Oxaloacetate (OAA),
acetyl CoA (aCoA)
Cit

Hydroxyethyl derivative

Enzyme
Pyruvate dehydrogenase (PDH) enzyme
complex (E1-3); active when
dephosphorylated (kinase / phosphatase)
E1: Pyruvate decarboxylase + TPP

Disulfide lipoic acid /

acetyl CoA

E2: Dhidrolipoyl transacetylase + lipoic

acid

Regenerated lipoic
acid / FAD

E3: Dihydrolipoyl DH + FAD, NAD,

CoASH

Citrate (Cit)

Citrate synthase

Aldol condensation

OAA, aCoA

Isocitrate (ict)

aconitase

Dehydration, hydration
Releases 1st of 3 NADH
and 1st CO2

Ca2+, ADP
Isocitrate, AMP, ADP,
Ca2+, low energy
charge

Oxidation and
carboxylation

Ict

-ketoglutarate (KG)

Ict DH

Oxidative
decarboxylation

KG

Succinyl CoA (sCoA)

-KG DH

Cleavage

sCoA

Succinate (Suc)

Suc thiokinase, sCoA synthase

Oxidation

Suc

Fumarate (Fum)

Suc dehydrogenase (only FAD linked

enzyme in TCA)

Hydration

Fum

L-Malate (L-Mal)

Fumarase

Oxidation

L-Mal

OAA

Mal DH

Action
Links EMP to TCA

Releases 2nd NADH and

CO2
Cuts high-energy
thioester bond GTP
Produces 2 ATP via
FADH2 in ETC
Adds H2O to double
bond of Fum
Releases 3rd NADH,
regenerates OAA

Stimulators / Activators
Allosterically: AMP,
CoASH, NAD, Ca2+,
low energy

AMP, NAD+

Inhibitors / Deactivators
Allosterically: ATP, acetyl
CoA, FA, NADH, high energy

Notes
Irreversible, in mitosol

ATP, NADH, succinyl CoA,

citrate, LCF acylCoA
Fluorocitrate, ATP

Rate-limiting / regulatory
step

ATP, NADH, high energy

charge

Irreversible, rate-limiting
step

ATP, GTP, NADH, SCoA,

Ca2+, arsenite
Substrate level
phosphorylation

ATP, Pi, Suc

Malonate, OAA
Reversible

NAD+

NADH

HEXOSE MONOPHOSPHATE SHUNT / PENTOSE PHOSPHATE SHUNT

1st alternative route for glucose oxidation

Summary
o
Oxidative:
3 G6P + NADP
3 pentose5P + 6 NADPH + 6 H+ + 3 CO2
Primarily anabolic
o
Non-oxidative:
2
X5P
+
Rbs5P
GA3P + 2 F6P
In cytosol, most active in adipose, RBC, adrenal cortex, testes and lactating mammary glands
o
Balanced:
3 G6P + 6 NADP 2 F6P + GA3P + 6 NADPH + 6 H+ + 3 CO2
Regulation
o
For 1 mole G:
6 G6P + 12 NADP 5 hexose6P + 12 NADPH + 12 H+ + 6 CO2
o
Based on demands for NADPH, Rbs5P and ATP

Clinical
Disorders
o
If NADPH need, non-oxidative phase generates compounds that can be easily reconverted to G6P
o
G6PDH deficiency
o
Most important regulator: NADP for G6PDH activity; high NADPH inhibits G6PDH

NADPH production from deficiency of G6PDH, may be genetically absent or partially active variant
o
G6PDH inhibited by levels of reduced glutathione; CHO intake = G6PDH activity

failure to maintain reduced glutathione (using glutathione reductase) for RBC CM integrity =
hemolysis
Mode
Substrate
Need for

failure to maintain normal oxidation state of iron in hemoglobin = methemoglobinemia = RBC cell
1
Rbs5P
Nucleic acid synthesis
membrane weakening = hemolysis
2
NADPH + Rbs5P
Steroid and lipid synthesis
o
Wenicke-Korsakoff Syndrome
3
NADPH
Reducing agent, detox

Loss of memory, partial paralysis secondary to thiamin deficiency, vitamin B1 deficiency

4
GA3P Pyruvate
Energy production

affinity of transketolase for TPP

Non-Oxidative

Oxidative

Step
Dehydration
Hydrolysis
Oxidative decarboxylation
Conversion
(Isomerization)
Conversion

Substrate

Product

Enzyme

G6P

6-phosphogluconolactone (6PGL)

G6P DH

6PGL lactone group

6-phosphogluconic acid (6PGA)

gluconolactonase

6PGA

Ribulose-5-phosphate (Rbls5P)

6-Phosphogluconate DH (NADP-linked)

Rbls5P

Ribose-5-phosphate (Rbs5P)

Phosphopentose isomerase (ketoisomerase)

Rbs5P

Xylulose-5-phosphate (X5P)
GA3P + sedoheptulose-7-phosphate
(S7P)
Erythrose-4-P (E4P) + F6P
GA3P + F6P

Phosphopentose epimerase

Transketolation 1

X5P + Rbs5P

Transaldolation
Transketolation 2

S7P + GA3P
X5P + E4P

Action
Produces 1st NADPH

Notes
Rate-limiting step

Produces 2nd NADPH

Transketolase

Donor: Ketose, Receiver: Aldose

Transaldolase
Transketolase

Donor: Aldose, Receiver: Ketose

URONIC ACID PATHWAY / GLUCURONIC ACID PATHWAY

2nd alternative pathway for glucose oxidation

Needed for pentose formation and metabolism of non-phosphorylated sugar derivatives

Catabolic, produces UDP-glucuronate for:

Clinical Conditions:
o
Essential Pentosuria L-xylulose secretion, genetic absence of LX DH, no physiologic consequences
o
GAG synthesis
o
Oxalosis too much xylitol, deposition of oxalate in brain and kidneys; following parenteral xylitol
o
Glucuronide formation through conjugation
o
Some polysaccharide synthesis
administration; xylitol in carrot, plum, spinach, as sweetener

Source of ascorbic acid except for man and guinea pigs

Step
Substrate
Product
Enzyme
Action
Notes
Isomerization
G6P
Glucose-1-phosphate (G1P)
Phosphoglucomutase
Formation
G1P + UTP
UDP-glucose (UDPG)
UDPG pyrophosphorylase
Oxidation
UDPG @ C6
UDP-glucuronate (UDPGU) (active glucuronate)
UPG DH (NAD-dependent)
Conversion
UDPGU
D-glucuronate (DGU)
hydrolase
Reduction
DGU
L-gulonate (LG)
LG DH (NADPH-dependent)
Change from D- to L- isomer
Most highly oxidized C is C1 of LG
Formation (3 steps)
LG
Ascorbic acid
Dehydration
LG
L-gulonolactone (LGL)
Aldonolactonase
Oxidation
LGL
2-keto-L-gulonolactone (2KLGL)
Gulonolactone oxidase
Conversion
2KLGL
L-ascorbic acid
Spontaneous
Oxidation
L-ascorbic acid
L-dehydro-ascorbic acid
Ascorbic acid oxidase (plants), heavy metals (humans)
Oxidation
LG
3-keto-L-gulonate (3KLG)
Keto-L-gulonate DH (NAD-dependent)
Decarboxylation
3KLG
L-xylulose (LX)
Conversion (2 steps)
LX
D-xylulose (DX)
Reduction
LX
Xylitol
LX DH (NADPH-dependent)
Oxidation
xylitol
DX
Xylulose DH
Phosphorylation
DX
D-xylulose-5-phosphate (DX5P)
xylulokinase
DX5P can be metabolized in HMP shunt

GLUCONEOGENESIS (GNG)

Synthesis of glucose from non-carb sources (lac, pyr, glycerol, glucogenic AA, odd-chain FA)
Both in cytosol and mitochondria in liver (90%) and renal cortex (10%)
Not a reverse of glycolysis/EMP; but 8 out of 11 glycolysis steps are reversible and are shared
o
Direct reversal of EMP = G = +20 Kcal/mol = very unfavorable thermodynamically
o
GNG = G = -9 Kcal/mol = feasible
4 unique rxns (pyruvate carboxylase (pyr CX), PEP CX, F1,6BP 1-phosphatase, and G6Pase) w/c circumvent the 3 irreversible glycolytic rxns (Hexokinase, PFK1, pyruvate kinase)
All inhibitors of EMP are activators of GNG and vice versa
Fxn: maintains blood sugar concentration, uses lactate and glycerol (end products of glycolysis and glycerol), excretes excess protons by kidneys during metabolic acidosis, recycles C skeletons of deaminated AA
Energetics: couples cleavage of cleavage of 6 high-energy phosphate bonds per glucose molecule
Reaction
Change in ATP / Glucose
Pyr OAA
-2 ATP
OAA PEP
-2 GTP (or ATP)
3PGA 1,3BPG
-2 ATP
Total
-6 ATP
o
Summary: 2 pyr + 4ATP + 2GTP + NADH +2H+ glucose + 2 NAD+ + 4ADP + 2GDP + 6Pi
Regulation
o
Enzyme compartmentation pyr kinase (cytosol), pyr CX (mito)
o
Substrate availability glucogenic AA and lactate
o
Allosteric regulation and feedback control

Pyr CX by aCoA, ATP

Pyr kinase if inhibited directs to GNG; by F1,6BP; ATP, alanine, free FA, aCoA (high energy)

F1,6BP1Pase by citrate, ATP; by AMP, ADP, F2,6BP

G6Pase by Pi and glucose (product inhibition)

o
Hormonal control

Induction of enzyme synthesis key GNG enzymes by glucocorticoids, by insulin (also induces EMP enzymes)

Covalent modification

Glucagon pyr kinase by phosphorylation, F2,6BPase by phosphorylation

Insulin GNG by cAMP levels = phosphorylation of F2,6BPase

Step
Conversion
Carboxylation
***Reduction
*** Reoxidation
Conversion
Conversion

Substrate
Lac
Pyr
OAA
Malate
OAA
PEP

Product
Pyr
OAA
Malate
OAA
PEP
F1,6BP

Dephosphorylation
Isomerization
Dephosphorylation

F1,6P
F6P
G6P

F6P
G6P
Glucose

Enzyme
LA DH, NADH
Pyr CX, biotin, aCoA, ATP, Mg2+, Mn2+
Mito mal DH
Cytosol mal DH
Cytosolic PEP CX, GTP, Mn2+
Enolase, phosphoglycerate mutase, 1,3-BPglycerate kinase, GA3P
DH, Phosphotriose isomerase, aldolase
F1,6BP 1-phosphatase
Phosphoglucoisomerase
G6Pase

GNG from Glycerol

o
Glycerol (product of TAG hydrolysis) phosphorylated + ATP by glycerokinase (not found in adipose) to
Glycerol-3P
o
Gly3P oxidized to DHAP by Gly3P DH + NAD
o
DHAP enters EMP
GNG from AA
o
C skels of glucogenic AA are degraded into pyr and TCA intermediates
o
Mito malate diffuses into cytosol then converted to OAA
GNG from Odd-# FA
o
Forms propionyl CoA (proCoA) after -oxidation
o
proCoA methylmalonyl CoA succinyl CoA TCA

Action

Notes
In mitochondria, circumvents conversion of pyr to PEP

Translocates mito OAA to cytosol

Liberates CO2
Reversal of glycolysis

Circumvents conversion of pyr to PEP

Allosterically activated by ATP, inhibited by AMP

Absent in skel musc, brain to trap free glucose

o
succinyl CoA malate
Cori cycle
o
Lactic acid reaches kidney and liver via blood
o
Lactate glucose
o
Glucose is released to blood glycolysis pyruvate
Glucose-Alanine Cycle
o
Muscle Alanine transaminates with KG = Glutamate, pyr in liver
o
Liver pyr glucose
o
Glucose leaves liver, used by extrahepatic tissues in glycolysis, forming pyr
o
Alanine may also be released directly by muscles in muscle protein breakdown

GLYCOGEN METABOLISM

synthesized and stored in cystolic granules in liver and muscle, higher conc in liver, greater % in muscle
polymeric nature easier sequestration of energy stores (unlike glucose)
liver glycogen maintains blood glucose via breakdown; 10% of weight is glycogen (higher in well-fed state), lasts 12-24 hours
muscle glycogen for fuel reserve; 2% weight as glycogen

GLYCOGENESIS (Synthesis)
Step
Substrate
Isomerization
G6P
Formation
G1P + UTP
Hydrolysis
UPDG + PPi
Formation
Old glycogen fragment or glycogenin
Elongation via
G from UDPG + primer
Transfer
Branching
7G chain

GLYCOGENOLYSIS (Degradation)
Step
Substrate
Phosphorolysis
Terminal 1,4 glycosidic bonds at
non-reducing end
Debranching
Glycogen chain
Glycogen chain

Product
Glucose-1-phosphate (G1P)
UDP-glucose (UDPG) + PPi
Glycogen primer
Elongated primer with G, UDP
Connects to C6

Product

Enzyme
Phosphoglucomutase
UDPG pyrophosphorylase
Pyrophosphatase
Glycogen initiator synthase
Glycogen synthase (GlyS)

Notes / Action

free G cannot accept a molecule of G from UDPG to initiate chain synthesis

Forms 14 glycosidic bonds,

Branching enzyme (-D-glucsyl-4:6 transferase /

oligo 1,41,6 glucantransferase)

Forms 16 glycosidic bonds, irreversible, at least 11G before transfer (4G

remains between branching), solubility, non-reducing ends = synthesis

G1P

Enzyme
Glycogen phosphorylase

Notes / Action
Rate limiting step, ends if 4G remaining on chain before branch

Shorter branch
G, glycogen chain

Glucose 4:4 transferase

Amylo 1,6 glucosidase

Transfers outer 3G of 4G of a branch to non-reducing end of another chain

Breaks 1,6 linkage, makes chain available for glycogen phosphorylase

Regulation

Glycogenesis

Glycogenolysis

Enzyme

Activity

GlyS D
GlyS I
cAMP-dependent protein kinase
Phosphoprotein phospatase
Phosphoprotein phospatase inhibitor
GlyP a
GlyP b
Phosphorylase kinase
cAMP-dependent protein kinase

Inactive
Active

State (Phosphorylated/
Dephosphorylated)
P
D

Active/Inactive
Active
Inactive
Active/Inactive

P/D
P
D
P/D

Action/Notes
G6P dependent
G6P independent
Interconverts GlyS D/I
Dephosphorylates GlyS D
Liver: dimer with pyridoxal PO4; Muscle: allosterically activated by ATP, G6P ( energy)
By phosphatase; Muscle: allosterically activated by AMP ( energy)
Activates GlyP b to a
With cAMP activates phosphorylase, 2R/2C tetramer

Phosphorylation Cascade and Hormonal Control

Hormonal status influences glycogen metabolism by affecting cAMP levels

cAMP activates cAMP-dependent protein kinase [1] activates phosphorylase b kinase phosphorylase b to a = glycogenolysis; [2] GlyS I GlyS D = glycogenesis

phosphorylated phosphoporotein phosphatase inhibitor inhibits phosphoprotein phosphatase GlyS I maintained

blood G insulin glucose use (EMP, TCA)

blood G glucagon create glucose (glycogenolysis, gluconeogenesis)

cAMP cascade promotes glycogenolysis / energy use

o
pro-cAMP: glucagon / epinephrine
o
anti-cAMP: Insulin is stimulates phosphodiesterase cAMP 5AMP

FRUCTOSE METABOLISM

Product of sucrose hydrolysis; 2nd most abundant dietary sugar

Pathway

Step
Phosphorylation
Cleavage

Major Pathway
(F1P Pathway)

Minor Pathway
Sorbitol
Pathway

Phosphorylation
Oxygenation
Reduction and
Phosphorylation
Phosphorylation
Reduction
Oxidation

Substrate
Fructose, ATP
F1P
DHAP
Glyceraldehyde, ATP
Glyceraldehyde
Glyceraldehyde
Glycerol
Fructose, ATP
Glucose
D-sorbitol

Product
Fructose-1-phosphate (F1P)
DHAP, glyceraldehyde
G3P
D-glycerate
Glycerol
Glycerol-3-phosphate
F6P
D-sorbitol
D-fructose

Enzyme
Fructokinase
Aldolase B
Triokinase
Glyceraldehyde DH (NAD linked)
Glyceraldehyde DH (NADH linked)
Glycerol kinase
Hexokinase

Notes / Action
Isoenzyme of aldolase A of EMP
For glycolysis
For glycolysis or gluconeogenesis
Serine production via hydroxypyruvate
For triglyceride synthesis or gluconeogenesis
In adipose & muscle, during fructose conc, enters EMP (pyruvate), or GNG (glucose)
For spermatozoa nutrition, eye lens, Schwann cells
Sorbitol impermeable to cell membrane, step impaired in diabetics soribtol = osmotic pressure,
cataract formation, peripheral neuropathy

Clinical Disorders

Hereditary Fructose Intolerance genetic deficiency of aldolase B = F1P = inhibits fructokinase, hepatic glycogen phosphorylase, aldolase A

Essential Fructosuria deficient hepatic fructokinase blood/urine fructose

Fructosemia deficient F1,6BP1P = F1,6BP in blood and urine

GALACTOSE METABOLISM

Product of lactose hydrolysis, from complex carb digestion

Step
Substrate
Product
Enzyme
Notes / Action
Phosphorylation
Galactose (Gal), ATP
Gal1P
galactokinase
Transfer
Gal1P + UDPG
UPDGal, G1P
uridyltransferase
UDPGal may donate Gal in synthetic pathways
Isomerization
UPDGal
UPDG
Gal-4 epimerase
UDPG used in uridyltransferase again
Disorders

Galactosemia excessive Gal; autosomal recessive

o
Galactokinase Deficiency - blood/urine/tissue Gal, in lens: reduced to galactilol cataract formation
o
Gal1P uridyltransferase Deficiency classic galactosemia, Gal1P and galactilol; liver cirrhosis, mental retardation, cataracts; omit milk @ infancy

LACTOSE METABOLISM

Synthesis

Degradation

Step
Conversion
Transfer
Degradation

Substrate
UDPG
UDPGal, glucose
UDPGal, N-acetyl glucosamine
lactose

Product
UDPGal
1,4 linkage
N-acetylgalactosamine
G, Gal

Enzyme
Gal-4 epimerase
Lactose synthase (galactosyl
transferase)
lactase

Notes / Action
In mammary gland
In intestinal brush border