GLYCOLYSIS & GLUCONEOGENESIS

HMP SHUNT

PYRUVATE DH

FA β-OXIDATION

CITRIC ACIDCYCLE

UREA CYCLE

USM

LE S

TEP

I PAT

HW

AYS

CYTO

SOL

MIT

OCH

ON

DRI

AL

MAT

RIX

H2O

H2O

NAD

NADH + H+ + CO2

NAD + CoA

NADH + H+ + CO2

GTP + CoA

FAD

FADH2

NAD

NADH + H+

H2O

GDP + Pi

ATP

AMP + PPi

H2O + CO2 + 2ATP

NAD + H2O

NADH + H+

H2O

FAD

FADH2

NAD

NADH + H+

AMP + PPi

H2O

Pi

H2O

Pi

ATP + CO2ADP + Pi

GDP + CO2

GTP

HS-CoA

HS-CoA + ATP

Carnitine

Carnitine

ADP

ATP

ADP

ATP

NAD + Pi

NADH + H+

ATP

ADP

H2O

ATP

ADP

CO2

TPP

NAD

NADH + H+

NADP

NADPH + H+ H2O

H+

NADP

NADPH + H+

HS-CoA

Glucose

Glucose-6-phosphate

Fructose-6-phosphate

Fructose-1,6-bisphosphate

Dihydroxyacetone phosphateGlyceraldehyde-3-phosphate

1,3-Bisphosphoglycerate

3-Phosphoglycerate

2-Phosphoglycerate

Phosphoenolpyruvate

PyruvateLactate DH

Lactate

CORI CYCLE

Oxaloacetate

Hydroxyethyl-TPP

Acetyl-lipoic acid

Acetyl-CoA

Lipoic acid

TPP

HS-CoA

Dihydrolipoic acid

FAD

FADH2

NAD

NADH + H+Citrate

cis-Aconitate

Isocitrate

α-Ketoglutarate

Succinyl-CoASuccinate

Fumarate

Malate

OxaloacetateAspartate

Glutamate

Most AAs

Argininosuccinate

Citrulline

Carbamoyl phosphate

Ornithine

Urea

H2O

Arginine

α-Ketoglutarate

α-Keto acid

Most AAs

Glutamate

α-KG

α-Keto acid

α-KG

NH4+

Fatty acid

Fatty acyl-CoA

Fatty acyl carnitine

Fatty acyl-CoA

Fatty acyl-CoAC-2Δ2 trans enoyl CoA

L-3-hydroxyacyl CoA

β-keto fatty acyl CoA

Acetyl-CoA

6-P-Gluconolactone6-P-Gluconate

Ribulose-5-PRibose-5-P

Glyceraldehyde-3-P

Xylulose-5-P

Sedohetulose-7-P

Erythrose-4-P

Hexokinase

Phosphoglucose isomerase

Phosphofructokinase

Aldolase

Triose phosphateisomeraseGlyceraldehyde

-3-P DH

Phosphoglycerate kinase

Phosphoglycerate mutase

Enolase

Pyruvate kinase(AR hemolytic anemia)

Pyruvate DH

Pyruvate DH

Dihydrolipoyltransacetylase

Dihydrolipoyl DH

Citrate synthase

Aconitase

Aconitase

Isocitrate DH

α-KG DH

Succinyl-CoA Synthetase

Succinate DH(aka ETC Complex II)

Fumarase

Malate DH

Fructose-1,6-biphosphatase

Glucose-6-phosphatase

Phosphoenolpyruvatecarboxykinase

Pyruvatecarboxylase

Ornithinetranscarbamoylase

Argininosuccinatesynthetase

Argininosuccinase

Arginase

Carbamoyl phosphatesynthetase

Acyl-CoA synthetase

Acyl-CoA DH

Δ2 Enoyl-CoA hydratase

L(+)-3-hydroxyacyl-CoA DH

Thiolase

Glucose-6-P DH(X hemolytic anemia)

Lactonase

6-P-gluconate DHPhospho-pentoseisomerase

Phosphopentoseepimerase

Transketolase

Transketolase

Transaldolase

Glutamate DH

Galactose-1-PFructose-2,6-bisphosphate

2,3-Bisphosphoglycerate

Glucose-1-P

Sorbitol Fructose

GalactoseGalactokinsase

(m

ild galactosemia)

Gal-1-P URIDYLTRANSFERASE

(severe galactosemia)

Fructose

Fructose

Ketone bodies

Orotic acid

UMP

UDP

dUDPCTP

PRPP

IMP

AMP GMP

Ribose-5-P

dUMP

dTMP

THF

DHF

Acetoacetate

β-hydroxybuterate

Acetoacetate Acetoacetyl-CoA

β-hydroxybuterate

Methylmalonyl-CoA

Propionyl-CoA

Odd-chain fatty acidsand branched chain amino acids: Valine Isoleucine Threonine Methionine

F1P

Glyceraldehyde

Fructokinase

(essential fructosuria)

Aldolase B

(fructo

se in

tolerance

)

Aldose reductase Sorbitol DH

Glucokinase in pancreatic β-cells & liver.

gestational diabetes. Acts as a glucose sensor.

Phosphofructokinase 2

Fructose bisphosphatase 2

Bisphosphoglyceratemutase

Phosphatase

Ribonucleotide Reductase

PRPP synthase

PRPPamidotransferase

Thymidylatesynthase

Propionyl-CoA carboxylase (Propionic acidemia)

Methylmalonyl-CoA isomerase (Methylmalonic acidemia)

Thiophorase

- X-linkedrecessive: buildup of carbamoyl phosphate -> increased orotic acid w/ hyperammonemia (vs. ortic aciduria)

Purine base production orreuse from salvage pathway.De novo requires aspartate,glycine, glutamine, and THF.

Orotic aciduria (AR) - can’t convert ortic acid to UMP due to a defect in orotic acid phosphoribosyltransferase or orotidine 5’-phosphate decarboxylase.

NO hyperammonemia (vs OTC

in urine, megaloblastic anemia that doesn’t improve with B12 or folic acid.

+allosteric activator ofgluconeogenesis

lysine and leucine (the only two pure ketogenic AA)

Used by RBCs to make 2,3-BPGused in hemoglobin. Bypasses ATP production.

B 5 -

Pantothenic

a

cid (CoA)

B

BMITOCHONDRIA

2 Acetyl-CoA

Succinyl-CoA Succinate

No mitochondria in RBCsso they can’t use ketones for energy.

B1

B1

B6

B1

B1

B12

VITAMINSB1 (Thiamine) - α-KG DH Transketolase Pyruvate DH

B2+) - Succinate DH

Pyruvate DH (via Dihydrolipoyl DH) Acyl-CoA DH

(Pyridoxine) - Transamination rxn - also used in synth of cystathionine, heme, niacin, GABA, histamine,dopamine

Poor feeding, vomiting, hypotonia,lethargy, dehydration, ANION GAPACIDOSIS.

Maple syrup disease?Requires all the cofactors of pyruvate DH?

N-acetylglutamate

Insulin

Glucagon

Hydroxyurea

Creatinine NO

6-mercaptopurine

DihydrofolatereductaseMethotrexate

(Trimethoprim inbacteria)

+Alosteric activator of carbamoyl phosphatesyntetase

Medium chain acyl-CoA dehydrogenase

- Hypoglycemia - Hypoketonemia - Hyperammonemia - decreased ATP leads to shut down of urea cycle

Skeletal muscle carnitine:

- Myoglobinemia - Weakness following exercise - Elevated muscle triglycerides (oil droplets in muscle on histo) - Hypoketonemia

B5 - Pantothenic acid (CoA)

32 ATP via malate-aspartate shuttle (liver and heart)30 ATP via glycerol-3-phosphate shuttle (muscle)

Mannose

Hexokinase