Ch. 14: Alt Pathways of Glucose Metabolism & Hexose Interconversions Flashcards
What is glucuronic acid? Essential part of what?
Glucose w/oxidized C6
GAGs
What reactions are glucuronic acid needed for?
Highly polar ➡️ detox rxns of insoluble compounds (bilirubin, steroids, drugs)
Enzymes used to synthesize glucuronic acid?
1) UDPG-dehydrogenase (UDP glucose ➡️ UDP glucuronic acid)
2) Glucuronyl-transferase (UDP glucuronic acid ➡️ glucuronides)
2 main products from conversion of D-glucuronic acid?
L-ascorbic acid (not in humans)
D-Xylulose 5-P (➡️ PPP)
Disorders of glucuronic acid metabolism:
L-gulonolactone oxidase deficiency?
Unable to convert L-gulonolactone ➡️ L-ascorbic acid
Requires Vitamin C in diet
Disorders of glucuronic acid metabolism:
NADP+ dependent xylitol dehydrogenase deficiency?
No conversion of L-xylulose ➡️ xylitol
Causes essential pentosuria (⬆️ L-xylulose in urine)
Why is metabolism of fructose important?
Unable to regulate fructose blood levels
Major pathway of dietary fructose metabolism?
D-fructose ➡️ fructose 1-P (fructokinase)
Fructose 1-P ➡️ D-glyceraldehyde (aldolase B)
Minor pathway of dietary fructose metabolism?
D-fructose ➡️ fructose 6-P (hexokinase)
Blocking which enzyme occurs in essential fructosuria? Hereditary fructose intolerance?
Fructokinase
Aldolase B
Which enzymes convert D-glucose ➡️ D-sorbitol ➡️ D-fructose? Cofactors for each rxn?
1) Aldose reductase, NADPH (when ⬆️ glucose)
2) Sorbitol dehydrogenase, NAD+
Characteristics of essential fructosuria?
Benign
⬆️ fructose in urine
Characteristics of hereditary fructose intolerance?
Traps fructose 1-P in cells
Hypoglycemia, jaundice, hepatomegaly, liver failure, hyperuricemia, lactic acidemia
Steps in metabolism of galactose? Enzymes at each step?
Galactose ➡️ galactose 1-P (galactokinase)
Galactose 1-P ➡️ glucose 1-P or UDP galactose (galactose 1-P uridyl transferase)
Disorders of galactose metabolism:
Galactosemia? Characteristics?
Galactose 1-P uridyl transferase deficiency
Galactosemia, galactosuria, liver damage, cataracts, intellectual disability
Disorders of galactose metabolism:
Galactokinase deficiency, characteristics?
Galactosemia, galactosuria
Galactose ➡️ ⬆️ galactitol (aldose reductase
Can cause cataracts
How is lactose synthesized?
UDP-galactose + glucose ➡️ lactose (lactose synthase)
Which 2 proteins make up lactose synthase?
Beta-D-galactosyltransferase (protein A)
alpha-lactalbumin (protein B)
Metabolism of amino sugars:
How is fructose 6-P ➡️ glucosamine 6-P?
Aminotransferase, with gln ➡️ glu
Metabolism of amino sugars:
End products of metabolism of glucosamine 6-P?
GAGs (chondroitins, heparin)
glycoproteins
Sialic acid
Gangliosides
Where does pentose phosphate pathway occur?
Cytosol
3 function of PPP?
1) supply NADPH
2) supply ribulose 5-P
3) generate glycolysis intermediates
PPP:
Steps from glucose 6-P ➡️ ribulose 5-P? Enzymes for each step?
1) Glucose 6-P ➡️ 6-phosphogluconate (G6P dehydrogenase)
2) 6-phosphogluconate ➡️ ribulose 5-P (6-phosphogluconate dehydrogenase)
1 NADPH generated at each step
2 diff pathways for ribulose 5-P?
1) ➡️ ribose 5-P (ribose 5-P isomerase) ➡️ nucleic acid biosynthesis
2) ➡️ xylulose 5-P ➡️ glycolysis intermediates
What is the important fxn of NADPH?
Provides reducing power ➡️ detox harmful by-products
3 examples of harmful oxidized by-products in mitochondria?
Superoxide
Hydrogen peroxide
Hydroxyl radical
3 enzymes NADPH brings back to normal state in mitochondria? (After they handle ROS)
Superoxide dismutase
Catalase
Glutathione peroxidase
What enzyme is important in liver for detox of drugs?
Cytochrome P450 reductase (uses FAD, FMN)
General pathway for phagocytic cell to attack bacteria?
1) Attachment of pathogen to phagocytic cell (IgG + cell receptor)
2) Ingestion of pathogen ➡️ lysosome + phagosome = phagolysosome
3) Pathogen destroyed w/ROS
How is nitric oxide (NO) synthesized? What is needed for the rxn?
L-arginine ➡️ L-citrulline (NO synthase)
Needs NADPH & BH4
What is the most common inherited enzyme deficiency known to cause human disease? What disease results from this deficiency?
G6PD deficiency
Hemolysis (occurs from impaired ability of erythrocytes to produce NADPH ➡️ can’t recycle oxidized enzymes)
What are causes of oxidant stress in erythrocytes ➡️ increases demand for NADPH?
Certain drugs
Infections
Fava beans
What are Heinz bodies?
Aggregates of damaged RBCs
What happens to G6PD function as RBCs age?
Compare normal enzyme to G6PD Mediterranean & A-
RBC age ➡️ G6PD fxn ⬇️
Normal: Oldest cells still have enough G6PD activity to protect against oxidative damage &a hemolysis
Abnormal: ⬇️ in G6PD A-, ⬇️⬇️ in G6PD Mediterranean
Which nucleotides can sugars be coupled to ➡️ activated sugars?
UDP
GDP
CMP
Which activated sugars make up the sugar-nucleotide pool? (Involved in glycoconjugate biosynthesis)
UDP-GlcNAc, UDP-Gal, UDP-GlcUA,
UDP-GalNAc, UDP-xylose, CMP-sialic acid,
GDP-fucose, GDP-mannose
4 sugar-nucleotide pool defects?
1) Type I CHO-deficient glycoprotein syndrome (CDGs I)
2) Gal-1-P uridyltransferase deficiency
3) Gal-4 epimerase deficiency
4) Leukocyte adhesion deficiency type II (LAD II)
5 steps of N-linked glycosylation?
1) pro synthesis starts (ribosomes) ➡️ polypeptide extruded into RER
2) branched oligosaccharides synthesized on dolichol pyrophosphate
3) oligosaccharide transferred to asparagine residue of pro
4) as pro moves through RER, CHO chain trimmed
5) Further trimming and/or adding monosaccharides in Golgi
What is I-cell disease?
Deficiency in enzyme needed to phosphorylate mannose of glycoprotein (usually used to target glycoproteins to be sent to lysosomes ➡️ instead, sent to surface)
Characteristics of I-cell disease?
Skeletal abnormalities
Restricted joint movement
Coarse facial features
Severe psychomotor impairment
What does GPI stand for? Where are GPI-anchored proteins?
Glycosylphosphatidylinositol
Anchored to cell membrane
3 stages of peptidoglycan synthesis?
1) Synthesis of N-Acetylmuramic acid (MurNAc) peptide chain
2) Synthesis of GlcNAc-MurNAc repeating units
3) Cross-linking of polymer side chains (via transpeptidase)
How do penicillins & cephalosporins function?
Inhibit transpeptidation rxn in cross-linking (acts as suicide substrate)
Has similar structure to substrate for enzyme ➡️ forms inactive, stable penicilloyl-enzyme complex
