Metabolism Small

+Glycine

-Amino-Levolinic Acid (ALA)

Porphobilinogen

Pre-Uro-Porphyrinogen

Heme +Fe

Proto-Porphyrin

Co-Pro-Porphyrinogen

Uroporphyrinogen III

ALA SYNTHETASE(Regulated Step)ALA

Mitochondria

Cytoplasm

OAA Citrate

cis-aconitate

Isocitrate

-KG

Succinyl-CoA

Succinate

Fumarate

Malate

GTP + CoA

FADH2

NADH

I-DH = ADP (low E state)

I-DH = ATP & NADH

Succinyl-CoA

NADH

ATP

CO2 + NADH

ISOCITRATE-DH

KG-DH

CITRATE

SYNTHASE

ATP

Acetyl-CoA

NADH

Acetyl-CoA

PDH

ATP

CO2 + NADH

Acetyl-CoA

CO2 + ATP

Mg

HIGH

ATP + Acetyl-CoA

State favors the

PC Reaction > PDH Rxn

in the liver

Irreversable, important in Regulation

AKG-DH

Citrate Synthase

Pyrivate Kinase

PFK

Hexo/Glucokinase

Glutamate DerivativesGlycineArginine

Histidine

Prolone

Aceto-Acetyl-CoA

Leucine

Lysine

Tryptophan

Tyrosine

Isoleucine

GABA: Via Glutamate Decarboxylation

Glutamate

ATP & NH4

Glutamine

+ NADPH + H Glutamate y-Semialdehyde Spontaneous Proline-5-carboxylateCyclicization

+ NADPH + H Proline

+ Glutamate

Ornithine + KG

UREA CYCLE

Arginine

KG + NH4 + NADPH + H

TRANSAMINASES

KetoAcid + Glu

All AAs + aKG

Asp + aKG Glu + OAA

Asn + Glu Gln + AspATP

Glutamate DerivativesReduction of AKG to Glutamate

Decarboxylation of Glutamtate to GABA

Amination of Glutamate to Glutimine

Reduction of Glutamte to Glutamate to Glutamate Semialdehyde

Tranglutamination of Glutamate Semialdehyde to Ornithine

Ornithine can enter the UREA CYCLE and produce Arginine

Spontansouse Cyclization of Glutamate Semialdehyde to Proline 5 Carboxylate

Reduction of Proline 5 Carboxylate to Proline

Phenylalanine / Tyrosine

Iso, Met, Thr, Val

Ala, Cys, Gly, Ser, Thr

Essential AAs

PVT TIM HALL

Phe

Val

Thr

Trp

Ile

Met

His

Arg

Leu

Lyse

Non-Essential AAs

3PG --> Ser Cysteine Gly

Pyruvate --> Ala

AKG --> Glu, Arg, Pro

Phe --> Tyr

OAA --> Asp --> Asn

Non-Essential AAs

Ser, Cys, Gly

Ala

Asp, Asn

Glu, Arg, Pro

Tyr

Glucose

G6P

F6P

F1,6DP

G3P #5 TPI DHAP

1,3DPG

3PG

2PG

PEP

Pyruvate

#1 HEXOKINASE

#2 PHOSPHO-GLUCOSE ISOMERASE

#3 PFK

#4 ALDOLASE

#6 GLYCERALDEHYDE-3-PHOSPHATE DH

#7 PHOSPHO-GLYCERATE KINASE

#8 PHOSPHO-GLYCERO-MUTASE

#9 ENOLASE

#10 PYRUVATE KINASE

1 ATP Used (Net = -1)

ATP

ADP

1 ATP Produced x2 = 2ATP (net = +2ATP)

NAD

NADH

Hb

Met-HbMETHEMOGLOBIN REDUCTASE

23BPG DIHYDRO-GLYCERO-MUTASE

23BPG DPG PHOSPHATASE

+ NADH LACTATE-DH Lactate + NAD

PK = F1,6BP activate

PK = Alanine + cAMP Glucagon inhibit favoring Gluconeogensis

Citrate Inhibits PFK

favoring Gluconeogensis

1 ATP Used (Net = -2)

1NADH Produced x2 = 2NADH

LDH recycles NAD under aneurobic condition

so we can continue Glycolysis and produce 2ATP/Glucose

1 ATP Produced x2 = 2ATP) (net = 0ATP)

Fructose

F1P

DHAP + Glyceraldehyde + NADH Glycerol + NAD

G3P

TRIOSE KINASE

FRUCTOKINASE

ALDOLASE B

G3PATP + Glycerol

G3P + ADP GLYCEROL KINASE

G3P SerineTHF N5N10-methyleneTHF

Glycine CO2 + NH4

N5N10-M-THF + dUMP THYMIDILATE SYNTHASE DHF + dTMP

dTTP

N5N10-M-THF + Glycine Serine + THF DIHYDROFOLATE REDUCTASE DHF

*MTX, TMPT

+ Acetyl-CoA + 2NADPH HMG-CoA Reductase Mevalonic Acid + NADP+

IPP + DPP

GPP + IPP

FPP + FPP

Squalene

Cholesterol + ErgosterolHormones

Bile Acids

VitimainD

~Sugar

~amide~Carbon Chain

C3|

C2

|C1

~Carbon ChainOH~Glycophinolipids

NH2~

OH~

C3|

C2

|C1

~Carbon ChainOH~Sphingosine

~OH

~amide

OH~~Carbon Chain

C3|

C2

|C1

~Carbon ChainCeramides

~amide

OH~

~OPO3

~Carbon Chain

C3|

C2

|C1 ~Choline

~Carbon ChainSphingomyelins

~ester

~OPO3

~Carbon Chain

C3|

C2

|C1

Glycerophosphlipids

~ester

~Choline

~Carbon Chain

C3|

C2

|C1OH~

OH~OH~

THF N5N10-methyleneTHF+H2O

Homocysteine + Serine + B6 Cystathione Cysteine Methionine

via SAM CH3

CH3-THF

Vit-B12THF

CYSTATHIONE

SYTHASE

METHIONINE

SYTHASE

Glucose

Pyruvate

Alanine (NH3)-KetoGlu

Glu(NH3)-Ketoacids

Amino Acids (NH3)

MUSCLE

Pyruvate Gluconeogenesis

Alanine (NH3)

Transamination

Glutamate (NH3)

aKG

to UREA Cycle

NH4

Oxidative Deamination

LIVERGLUCOSE

ALANINE CYCLE

to Muscle

Glucose

PYRUVATE

CARBOXYLASE

ATP + CO2

ADP + pi

Malonyl-CoA

NUCLEOTIDE

PRECURSOR

FumerateOxidative Deamination of Glu

GLUTAMATE-DH

NADH

NH4

NAD

To Urea

Cycle

Phenylalanine

(Catecolamines, Melanin, Thyroxine)

TCA

(Niacin = B3, Serotonin = 5HT, Melatonin)

Creatine, Urea, NO

pi +

G6-PHOSPHATASE

H2O +

pi +

F1,6,BISPHOSPHATASE

H2O +

CO2 + PEP

PEP-CARBOXYLASE

OAA

MALATE-DH

Malate

NADH

NAD MALATE-DH

GDP

GTP

F2,6BP AMP F1,6BP

Glucagon [cAMP] Glucagon/cAMP activate F16BPase

(F26Bisphosphatase)

PFK = F6P, AMP, F26BP

PFK = ATP, Citrate

[cAMP] Glucagon(F26Bisphosphatase)

Glucagon/cAMP inhibit PFK

Phe PHENALALANINE HYDROXYLASE Tyr TYROSINASE Melanin

Homogentisate

HOMOGENTISIC ACID OXIDASE

fumarylacetacetate

fumarate

TCA

TERTRAHYDROBIOPTERIN

*PKU here

*Alkaptonuria here

*Albinism here

NH4 + CO2

UREA

CYCLE

Argino-Succinate

Arginine

Ornithine

Citrulline

UreaH2O

NH2

CO OPO3

Carbamoyl Phosphate

ORNITHINE

TRANSCARBAMYLASE

Ornithine + Carbomyl Phosphatate Citrulline

Fumerate

Aspartate

Liver MitochondriaCytoplasm

OT

G6P

G6P-DH

6-Phospho-gluconolactone

GLUCONOLACTONASE

6-Phospho-gluconate

6PHOSPHO-GLUCONATE-DH

R5P

( xylulose )

R5P-ISOMERASE R5P-EPIMERASE

R5P

TRANSKETOLASE

TRANSALDOLASE

TRANSKETOLASE

G3P + F6P

oxidative

phase

NADP + 2GSH

NADPH + GS-SG

2GSH + HOOH

GS-SG + 2H2OScavangingGlutathion Reductase

NADPH

NADP

non-oxidative

phase

PPP/HMP Shunt

TGalactose + ATP GALACTOKINASE Gal-1P ADPGalactitol

ALDOSE REDUCTASE

URIDYL0TRANSFERASE

GAL-1P

UDP-GAL-4-EPIMERASE

UDP-Glucose UDP-Gal

Glu-1P PHOSPHOGLUCOMUTASE

GLUCOSE 1P

URIDYL TRANSFERASE4-Glu-1-OPPiO-Uridine

(4OH-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd (4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd

6OH

(Reducing End

with a free OH)

GLYCOGEN SYTHASE + (4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd +

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)

O6

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ Non-reducingEnd

Non-reducing

End

PHOSPHORYLASE

G1P

PHOSPHOGLUCOMUTASE

G6P

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH

O6

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ Non-reducingEnd

Non-reducing

End

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1)

O6

HO~4-Glu-1~

(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1) + Glucose

DEBRANCHING ENZYME (Tranferase Activity)

The glucose in -(1,6)-linkage at the branch is then removed by the action of glucosidase.

This glucose residue is uncharged

The transferase activity removes the terminal 3 glucose residues of one branch

and attaches them to a free C-4 end of a second branch.

DEBRANCHING ENZYME (GLUCOSIDASE ACTIVITY

DEBRANCHING ENZYME

Aminoglucotransferase (branching enzyme)

(+ Glygogen -1)

TYPE 1 GLYCOGEN STORAGE DISEASE = Von Gierkes disease

df @ Glucose-6- phosphatase @ Liver and kidney.

Severe fasting hypoglycemia

Lactic acidosis. Hepatomegaly (100%)

Short stature (90%). Delayed puberty.

Bleeding diathesis (especially epistaxis).

Hepatic adenomas (75%)

Renal failure and gout in 20s and 30s.

TYPE 2 GSD = Pompes disease

df @ -1,4-glucosidase (acid maltase) @ All organs (enzyme is in lysosomes).

Progressive muscle weakness.

Breathing and feeding difficulties.

Hyporeflexia or areflexia due to glycogen accumulation in spinal motor neurons.

Cardiomegaly leading to congestive heart failure

death before the age of 2

TYPE 3 GSD = Coris disease

df @ Debranching enzyme (-1,6-glucosidase) @ Muscle and liver.

Similar to type I without lactic acidosis

Hypoglycemia

Hepatomegaly

Delayed (ultimately normal) growth.

Symptoms usually regress in adulthood

Type 5 GSD = McArdles disease

df @ Myophosphorylase @ Muscle.

Muscle weakness and cramps after exercise

Myoglobinuria (burgundy urine) after exercise

OVERVIEW OF METABOLISM

TRIOSPHOSPHATE ISOMERASE

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