Amino Acids, Peptides, Protein Structure + Amino Acid Metabolism

amino acid properties

has amino (NH₃⁺) group & carboxylic acid (COOH) group

pKa values of all functional groups of amino acid/peptide dictate net change at a given pH

-COOH pKa ~2, NH₃ pKa ~9

-in aqueous solution, charged & uncharged forms of COOH & NH₃⁺ exist in equilibirum

-pH below pKa: protonated

-pH above pKa: deprotonated

essential amino acids

PVT TIM HALL

semiessential amino acid

arginine

depend on essential amino acids

cysteine (F) and tyrosine (M)

polar amino acids

STNYQ (Start The New Year Quickly)

nonpolar amino acids

G, A, V, C, P, L, I, M, W, F

positive amino acids (basic)

KRH

negative amino acids (acidic)

aspartic acid, glutamic acid

glucogenic vs ketogenic

glucogenic: converted to glucose

ketogenic: form ketone bodies (leucine, lysine)

both glucogenic & ketogenic

Ile, Phe, Tyr, Trp, Thr

how are proteins built

-mRNA carries genetic info from nucleus into cytoplasm

-txn & tln

transcription

passage of info from DNA to mRNA

-codons/triplets (3 base sequences arranged in linear sequence along DNA)

-gene (linear stretch of DNA that codes for a specific protein)

translation

mRNA directs assembly of amino acid sequence to form protein

-occurs on ribosomes in cytoplasm or attached to ER

amino acids linked by

peptide bonds

primary structure

sequence of amino acids in polypeptide chain

secondary structure

folding of short (3-30 residue), continuous segments of polypeptide (half in ß sheet or α helix, half in loops/turns/bonds)

-ß sheet or α helix

tertiary

assembly of secondary units into larger functional units (polypeptide chain)

quaternary structure

the number and types of polypeptide units of oligomeric proteins and their spatial arrangement (protein)

α helix

-stability from hydrogen bonds between O of peptide bond carbonyl & H of peptide bond N of 4th residue

-amphipathic (may have hydrophobic R groups projecting from one side along central axis & hydrophilic R groups projecting from other side)

-clusters of amphipathic helixes can create channels through hydrophobic cell membranes for passage of polar molecules

ß sheet

stability from H bonds between carbonyl O and amide H; formed between adjacent segments of ß sheet

protein folding

-assisted by chaperons

-disulfide bonds between and within polypeptides stabilize tertiary or quaternary structures

-initiated by sulfhydryl oxidase (catalyzes oxidation of cysteine residues to form disulfide bonds)

amino acids flow through a pool

no storage form; turned into new body protein, specialized products, or oxidized

removing nitrogen in amino acid metabolism

1) transamination moves the amino group (amino acid + α-ketoglutarate —(aminotransferase)→ α-ketoa acid + glutamate

2) glutamate dehydrogenase frees ammonia (glutamate —(glutamate dehydrogenase)→ α-ketoglutarate + NH₄⁺

ALT (alanine aminotransferase)

alanine ⇌ pyruvate

-conc. in liver

AST (aspartate aminotransferase)

glutamate ⇌ aspartate

-in liver, heart, skeletal muscle

when hepatocytes damaged

serum ALT/AST rise

free ammonia

toxic, especially to brain; crosses BBB and astrocytes trap as glutamate

moving ammonia in amino acid metabolism

glutamine (main N carrier in blood)

-in liver: glutaminase → glutamate + NH₄⁺, NH₄⁺ enters urea cycle

-in kidney: glutaminase → NH₄⁺ excreted in urine

glucose-alanine cycle (muscle N to liver)

-alanine carries C and N from muscle to liver; glucose returns from liver to muscle

urea

the body’s nitrogen export form

-made in liver, carried in blood, excreted by kidney

-first N from free ammonia, second N from aspartate, C from HCO₃^-

-neutral, water soluble, non toxic

urea cycle

-in liver; starts in mitochondria, ends in cytosol

-3 ATP per urea

-NH₄⁺ + HCO₃^- + 2 ATP → cycle → fumarate

“krebs bicycle”

links urea & TCA cycles

-urea cycle —fumarate→ Krebs

-Krebs —aspartate→ urea cycle

hyperammonemia

occurs when urea cycle fails

-inherited (urea-cycle disorders)

-acquired (liver failure)

carbon skeletons

-7 entry points into central metabolism

-ketogenic (leucine & lysine): skeleton → acetyl CoA or acetoacetate → ketone bodies or fatty acids

-glucogenic: skeleton → pyruvate or TCA intermediate → net glucose

branched chain amino acids oxidized in muscle

Leu, Ile, Val —(BCAA)→ α keto acids —(BKCD)→ acyl CoAs

-BKCD (branched chain α-keto acid dehydrogenase)

-BKCD deficiency: maple syrup urine disease

musce protein becomes glucose in fasting

prolonged starvation spares protein

1) brain gets energy from ketone bodies after several days

2) less glucose needed, less protein broken down

made by decarboxylation of an amino acid

dopamine, serotonin, histamine, GABA

specialized products

-tyrosine → catecholamines

-tryptophan → serotonin → melatonin

-histidine → histamine

-glutamate → GABA

-arginine → citrulline + NO

-glycine → creatinine & heme