SUMMARY OF METABOLIC PATHWAYS

Prepared by: GGNC

PATHWAY FOR OCCURS IN SUBSTRATE END PRODUCT RATE-LIMITING CLINICAL CORRELATES

GLYCOLYSIS Major pathway for Cytoplasm, in all cells glucose Pyruvate or Lactate, depending on Reaction: -Arsenic Poisoning (Pentavalent Arsenic)
glucose metabolism the presence of mitochondria and Fructose-6-phosphate  fructose-1,6-bisphosphate -Pyruvate Kinase Deficiency
that converts availability of oxygen -Muscle Phosphofructokinase Deficiency
glucose into 3 Enzyme: -Pyruvate Dehydrogenase Deficiency
carbon compounds Phosphofructokinase-1 (PFK-1) -Chronic Alcoholism
to provide energy
TRICARBOXYLIC ACID -Provides majority -in all cells with Acetyl CoA CO2 Reaction:
PATHWAY of ATP for energy mitochondria GTP Isocitrate  α-ketoglutarate
(KREBS CYCLE or CITRIC -gluconeogenesis - mitochondrial matrix NADH
ACID CYCLE) from skeletons of except for succinate FADH2 Enzyme:
AA dehydrogenase (inner Isocitrate Dehydrogenase
Building blocks for mitochondrial membrane)
AA and heme
(succinyl CoA)
CORI CYCLE -Conversion of Lactate Glucose
lactate to glucose
--lactate generated
during anaerobic
metabolism
--lactate brought to
the liver 
converted to
glucose via hepatic
gluconeogenesis
--glucose brought
back to muscles
and RBC
GLUCONEOGENESIS -Production of -occurs in the liver (90%) Pyruvate Glucose Reaction: -Glucosuria
glucose from the and the kidney (10%) fructose-1,6-bisphosphate  Fructose-6-phosphate -Alcoholism and Hypoglycemia
following -during prolonged fasting, -Hypoglycemia during Pregnancy
interactions: the kidneys contribute as Enyme: -Hypoglycemia in the Neonate
1. intermediates of much as 40% Fructose-1,6-bisphosphatase
glycolysis and the - occurs in both
TCA mitochondria and
2. glycerol from cytoplasm
triacylglycerols
3. lactate through
the Cori Cycle
4. carbon skeletons
(α-ketoacids) of
glucogenic amino
acids
GLYCOGENESIS Synthesis of new -occurs in the liver and -UDP-glucose Glycogen Reaction: Glycogen storage diseases
glycogen molecules the muscle -ATP and UTP Elongation of glycogen, addition of α (14) bonds
from α-D-glucose -occurs in the cytosol -glycogenin: a core, primer
protein Enzyme:
Glycogen synthase
GLYCOGENOLYSIS Shortening of -occurs in the liver and -Glycogen -glucose-1-P and free glucose Reaction: Glycogen storage diseases
glycogen chains to the muscle -leaves about 4 glucose -liver: can release free glucose to Removal of glucose (breaks α (14) bonds)
produce molecules -occurs in the cytosol residues before a branch circulation
of α-D-glucose point  limit dextrin -muscle: limited to glucose-6-P Enzyme:
within muscle only Glycogen phosphorylase
-free glucose  produced during
the debranching process
GALACTOSE Galactose UDP-glucose? -Galactokinase Deficiency
-Classic Galactosemia
FRUCTOSE Fructose Dihydroxyacetone phosphate -Essential Fructosuria
(DHAP) + Glyceraldehyde? - Fructose Intolerance
PENTOSE PHOSPHATE Production of Cytoplasm Glucose-6-Phosphate -Ribose-5-Phosphate Reaction: -Gluthathione
PATHWAY (HEXOSE important Fructose-6-Phosphate Glucose 6-Phosphate  6-Phosphogluconate -Glucose-6-Phosphate Dehydrogenase
MONOPHOSPHATE intermediates Glyceraldehyde-3-Phosphate Deficiency
SHUNT) -produces NADPH -NADPH Enzymes: -Chronic Granulomatous Disease
 provides Glucose-6-P dehydrogenase
electrons for:
1. FA and steroid
biosynthesis
2. reduction of
gluthathione
3. cytochrome P450
4. WBC respiratory
burst
5. Nitric Oxide
Synthesis
- produces ribose-5-
phosphate used for
synthesis of
nucleotides
-metabolic use of 5-
carbon sugars
FATTY ACID SYNTHESIS Formation of -Cytosol 1 Acetyl CoA Palmitate Reaction:
palmitate (16:0) -Major: Liver and 7 Malonyl CoA NADPH and Acetyl CoA + ATP  Malonyl CoA
Lactating Mammary ATP
Glands Enzyme:
-Minor: Adipose Tissue Acetyl CoA Carboxylase
TAGs SYNTHESIS Formation of Liver and adipose tissue -Glycerol-3-Phosphate Triglyceride
triglycerides -3 fatty Acyl CoA
BETA-OXIDATION OF -removal of Acetyl - in the mitochondria of Palmitate, NAD+ 8 Acetyl CoA Reaction: -Fatty Liver
FATTY ACIDS CoA fragments almost all cells 7 FADH2 Fatty Acyl CoA + Carnitine  Fatty Acyl Carnitine + -Carnitine Deficency
from the ends of **fatty acid activation FAD,ATP 7 NADH CoA -Medium-Chain Fatty Acyl-CoA Dehydrogenase
fatty acids occurs in the cytosol (MCAD) Deficiency
-Acetyl CoA can -exceptions are neurons, Enzyme: -Jamaican Vomiting Sickness
enter the citric acid RBC, testis, kidney Carnitine Acyltransferase I -Refsum’s Disease
cycle medulla -Zellweger’s Syndrome
-generates NADH -X-linked Adrenoleukodystrophy
and FADH2 that can
enter the ETC
KETOGENESIS Converts Acetyl In liver mitochondria Acetyl CoA Ketone Bodies Reaction:
CoA to ketone -Acetoacetate and β- Acetoacetyl CoA + Acetyl CoA  HMG-CoA
bodies hydroxybutyrate
- Acetone Enzyme:
HMG CoA synthase
KETOLYSIS Use ketone bodies Peripheral tissues with β-hydroxybutyrate Acetyl-CoA -Ketoacidosis
as fuel for mitochondria can oxidize
extrahepatic tissues ketone bodies
especially during -skeletal muscle
fasting -renal cortex
-brain
CHOLESTEROL De novo synthesis -Virtually all cells, in the Acetyl CoA Lanosterol  Cholesterol Reaction: -Statins
SYNTHESIS of cholesterol cytosol and smooth ER NADPH HMG CoA Mevalonate
- majority in the liver and ATP
intestines Enzyme:
HMG CoA Reductase
STEROID HORMONE Cholesterol is the In the smooth ER of the ff: Cholesterol Steroids hormones Reaction:
SYNTHESIS precursor of all -adrenal cortex Pregnenolone Cholesterol  Pregnenolone
steroid hormones -ovaries and testes
-glucocorticoids -placenta Enzyme:
-mineralocorticoids Desmolase
-sex hormones
(testosterone and
estradiol)
UREA CYCLE For removal of liver NH3 Urea Reaction: -Hereditary Hyperammonemia
(KREBS-HENSELEIT CYCLE nitrogenous waste Aspartate CO2 + NH3  Carbamoyl Phosphate -Acquired Hyperammonemia
or ORNITHINE CYCLE) products in the CO2
body Enzyme:
Carbamoyl Phosphate Synthetase I
HEME SYNTHESIS -In almost all tissues Heme Reaction: -Porphyrias
-initial and last three Glycine + Succinyl CoA  δ-Aminolevulinic Acid -Sideroblastic Anemia with Ringed Sideroblasts
steps: mitochondria -Iron Deficiency
-intermediate steps: Enzyme: -Lead Poisoning
cytosol ALA Synthase
-predominant sites: liver
and bone marrow
HEME CATABOLISM Heme to urobilin or -reticuloendothelial Heme Stercobilin -Unconjugated Hyperbilirubinemia
stercobilin system, particularly in the Urobilin -Conjugated Hyperbilirubinemia
liver and spleen -Van Den Bergh Reaction
DE NOVO PURINE Enzyme:
SYNTHESIS Glutamyl PRPP amidotransferase
DE NOVO PYRIMIDINE Enzyme:
SYNTHESIS Carbamoyl Phosphate Synthetase II (CPS-II)