Lecture 17: amine and nucleotide metabolism

Utilizing amino acids in the cell:repurposing _____/____ backbones for specialized functions

carbon/nitrogen

Repurposing carbon/nitrogen backbones of amino acids to make

heme, biological amines, nucleotides

Specialized nitrogen molecules require ____

repurposing

Problem: with nitrogenous rings for light absorption, building them is

expensive

Solution to the expensive process of building nitrogenous rings

utilize simple nitrogen-containing compounds to build repeated structures

Nitrogenous ring synthesis: step 1: Build ___

a pyrolle from metabolic intermediates

Nitrogenous ring synthesis: step 2: Link 4 together to form a ___ ____

linear tetrapyrrole

Nitrogenous ring synthesis: step 3: Close the ring to form ____

porphyrin

Nitrogenous ring synthesis: step 4 Load specific ___ ___ to the center of the porphyrin ring

metal ion

Porphyrins

strongly absorb light in the visible spectrum

Porphyra geek word for

purple

Most abundant porphyrin in vertebrates

heme

Tetrapyrroles are derived from ___ and ___

glycine and succinyl-CoA

Aminolevulinate

dimerized then tetramerized to form a tetrapyrrole

Defects of enzymes in the biosynthetic pathway lead to ___

buildup of precursors

Porphyria

diseases linked to toxic intermediate building in erythrocytes, body fluids, liver (lacking one of 8 enzymes to build heme)

Symptoms of porphyria include

abnormal sensitivity to light, anemia (low iron in blood), receding gums, fluorescent teeth, dark red urine

Degradation of heme (black/purple) yields ___ and ___

biliverdin (green) and bilirubin (yellow)

when heme is broken down what happens to Fe2+

recycled

Degradation of heme is the only reaction in the human body producing ___

CO

Biliverdin and bilirubin removed as

waste

Bilirubin characteristics

highly non-polar, pyrrole rings are very stable (have to invest too much to recapture stored energy)

Bilirubin characteristics: pyrrole rings

very stable

Bilirubin

potent antioxidant in the blood

Buildup of bilirubin causes ___

yellowing of the eyes and skin (jaundice)

bilirubin is not

soluble

Attach ___ ____ _____ to make bilirubin more soluble

two glucuronic acids

To breakdown bilirubin in bile: gut microbiome digests to ___

stercobilin

Bilirubin breakdown: most stercoblinin (90%) removed in ___

feces (red-brown color)

Bilirubin breakdown: remaining 10% oxidized to ___

urobilin in urine (yellow color)

Amino acids are direct precursors to ___

biological amines

Biological amines

generated by decarboxylation of amino acids

Biological amines function

hormones and/or neurotransmitters

examples of biological amines

dopamine, norepinephrine, epinephrine, histamine, serotonin, GABA

dopamine

norepinephrine

epinephrine

GABA

serotonin

Histamine

PLP (Vitamin B6)

cofactor for transamination and decarboxylation

PLP acts as ___

electron sink

Different enzymes use PLP to attack ___

different functional groups

Tyrosine is a hub for

catecholamines (for making neurotransmitters)

Dopamine is a

neurotransmitter

neurotransmitter

chemcial signal that facilitates neuronal communication

Parkinson’s patients lose ___

dopamine-producing neurons

used to treat Parkinson symptoms

L-DOPA

Tryptophan and glutamate yield ___

distinct neurological signals

Serotonin and GABA

neurotransmitters

Histidine becomes ___ during immune response

histamine

Histamine

triggers vasodilation and allergic responses

Antihistamines

block histamine receptors

Seterotin and GABA are also

neurotransmitters

first step in polyamine synthesis

decarboxylation

Long, positively charged molecules that stabilize the negative backbone of DNA and RNA

Polyamines

Polyamines stablize the ___ ___ of DNA and RNA

negative backbone

DFMO inhibits ___

ornithine decarboxylase

Take Home: amino acids are not just for protein synthesis or energy; their chemical structures serve as the backbone for

communication and oxygen-transport networks

Nucleotide monophosphates

monomers of nucleic acids

ATP is an example of a

nucleotide

Nucleotide

nitrogenous base, pentose sugar, phosphate group

Nucleoside

nitrogenous base and pentose sugar (NO PHOSPHATE GROUP)

Alphabet for biological information includes

five nitrogenous bases

Five nitrogenous bases

adenine, guanine, cytosine, thymine, uracil

cytosine (C)

thymine (T, in DNA)

uracil (U, in RNA)

adenine (A)

guanine (G)

deoxyribose (in DNA)

ribose (in RNA)

PRPP

donor of ribose-phosphate unit

PRPP formed from ___

ribose-5-phosphate and ATP

Ribose-5-phosphate must be activated at

C1

Sugar First: bases are built stepwise onto PRPP

purine

Base First: precursor base synthesized then added to PRPP

pyrimidine

Purine biosynthesis ___ first

Sugar

purine is made up of

co2, aspartate, formate, glutamine, formate, glycine

Purine ring synthesized onto ___

ribose

Purine ring derived from ___

amino acids, N10-Formyl-THF, CO2

Synthesis of inosinate costs ___

5 ATP

___ and ___ are synthesized from IMP

AMP and GMP

Inosinate (IMP) is a ___ point

branch point

AMP requires ___

GTP hydrolysis

GMP requires ___

ATP hydrolysis

Relying on the opposite NTP for energy naturally

balances the pools

purine biosynthesis: inhibit the commitment step of the common pathway

IMP, AMP, GMP

___and ___ inhibit the entry point enzymes for their specific synthesis from IMP

AMP and GMP

Purine production remains ___so the pools are relatively equal for DNA and RNA synthesis

balanced

Uracil is the ___ _____ (point)

entry point

uracil: entry point modified to form ______ or _______ (___)

cytosine or thymine (DNA)

Pyrimidine biosynthesis ___ first

Base

Pyrimidine ring synthesized as ___ ____

base precursor

Pyrimidine ring derived from ___

carbamoyl phosphate and aspartate

Carbamoyl phosphate synthetase I (CPS I) is in the

mitochondrial matrix

Carbamoyl phosphate synthetase II (CPS II) found in

cytosol

CPS II: ____ never leaves the enzyme

ammonia

CPS II structure

a large channel links active sites

pyrimidine biosynthesis: what is the precursor base

orotate