Nucleotide Metabolism - Lecture 4

Catabolism

set of reactions by which simple molecules (biomolecules or monomers) undergo combustion to generate energy

Metabolic pathways

these pathways are both interdependent and tightly regulated

Metabolic pathways - shared intermediates

many of these among many pathways

Metabolic pathways - distinct regulatory enzymes

these enzyme(s) are used for each metabolic pathway

intermediates for cellular respiration

majority of pathways generate these for cellular respiration

Cellular respiration

series of metabolic pathways that convert carbon fuels into CO2 and H2O to generate energy

Cellular respiration - ATP

Energy used from carbon fuels to power ___ regeneration

Cellular respiration - biomolecule monomers

biomolecule ________ (or components) enter cellular respiration at different points

Where Nitrogenous Base Metabolism Occurs

occurs within liver mitochondria

Nitrogenous Base Metabolism

pathway differs depending on the type of nitrogenous base (purine or pyrimidine)

Nitrogenous Base Metabolism - urine

final products from either pathway can be excreted from body into _____

Nitrogenous Base Metabolism Pyrimidine Four steps

Deamination

Dehydration

Hydraulic ring opening

Hydrolysis

Schematic of the pyrimidine pathway!

What happens to B-alanine

converted into malonyl CoA or excreted into urine

can also be converted to acetyl CoA for citric acid cycle

malonyl CoA

an intermediate of fatty acid synthesis

What happens to Β-aminoiosbutyrate

converted into succinyl CoA or excreted in urine

Succinyl CoA

intermediate of the citric acid cycle

Acetyl CoA and succinyl CoA

both major metabolic intermediates

Steps of Nitrogenous Base Metabolism: Purines

1. Deamination

2. Inosine cleavage

3. Oxidation

Schematic pathway of purine catabolic pathway

Uric acid destination

this acid is sent to kidneys via bloodstream, then excreted in urine

Normal plasma levels

between 2.4 and 7 mg/dL

- if higher, crystallized and precipitates out, depositing into joints

Allantoin

most animals oxidize uric acid into _________ - improves stability

Regulation of nitrogenous base metabolism

impacted by nitrogen availability; sensing glutamate and glutamine

Regulation of nitrogenous base metabolism - Rate limiting enzynme

primarily controls the pathway of nitrogenous base metabolism

Dihydropyrimidine dehydrogenase

Rate limiting enzyme for pyrimidine

- transcription factor p53 suppresses gene expression

Xanthine Oxidase

rate limiting enzyme for purines

- transcription factor ModE suppresses gene expression (purine analogs)

Purine analogs (like allopurinol)

prescribed to control enzyme activity

If ribose, enters pentose phosphate pathway as ribose 5-phosphate

Generates intermediates for glycolysis or gluconeogenesis

Reactions parts of the pathways non-oxidative phase

Pentose phosphate pathway

Important set of reaction that generates NADH and pentoses

- links glycolysis (and cellular respiration) with nucleotide synthesis

NADPH

coenzyme with reducing power; can chemically reduce other molecules)

Where the pentose phosphate pathway operates

operates in both prokaryotic and eukaryotic cells

Highest activity of pentose phosphate pathway in human

highest activity of this pathway in humans is in the liver, adipose tissue, and red blood cells

Why pentose phosphate pathway unusual

This pathway is unusual because no ATP is produced or used

How nucleotide sugar is metabolized

During nonoxidative phase, ribose 5-phosphate converted into fructose 6-phosphate and glyceraldehyde 3-phosphate

Enzymes Transketolase and transaldolase

two enzymes required for metabolism of nucleotide sugar

Metabolism of nucleotide sugar products

products of this metabolism directed into glycolysis (generates ATP) or gluconeogenesis (generates glucose), depending on the cells needs

Deoxyribose metabolism

sugar cleaved by deoxyribose-phosphate aldolase (DERA)

What deoxyribose metabolism produces

generates acetaldehyde and glyceraldehyde 3-phosphate

acetaldehyde and glyceraldehyde 3-phosphate

intermediates of alcoholic fermentation and glycolysis, respectively

Where deoxyribose-phosphate aldolase (DERA) enzyme is in humans

this enzyme in humans is mainly expressed in the liver, lungs, and colon