Amino Acid Degradation

dietary proteins

turnover of cellular proteins

sources of amino acids

new proteins

nitrogenous compounds

amino acids are used as building blocks for ? and to make other ? such as the bases found in nucleotides

degraded

when cells have too many amino acids available, they are ? because they cannot be stored or excreted

essential amino acids

amino acids that must be obtained from diet since they cannot synthesize all the amino acids

histidine

isoleucine

leucine

lysine

methionine

phenylalanine

threonine

tryptophan

valine

types of essential amino acids

stomach

intestine

proteolytic enzymes (proteases)

dietary proteins are cleaved first in the ? and then in the ? by ?

intestinal cells

the amino acids and tri-/di-peptides that are formed are absorbed by the ?, where the peptides are further degraded into amino acids and released into blood

protein degradation

often used as a means of regulating cell processes

ubiquitin

proteins targeted for degradation are tagged with this small protein

ubiquitin

effective in marking a protein for degradation

Huntington’s disease

some forms of Parkinson’s disease

types of pathological conditions that are associated with proteins that are not removed and thus accumulate and aggregate

amino group

to break down amino acids, first the ? is removed

glucose

one of TCA cycle intermediates

acetyl-CoA

once the amino group is removed from the amino acid, the carbon skeleton is metabolized to ?, ?, and ?

a-ketoglutarate

the amino group of most amino acids is transferred to ? to form glutamate

glutamate

the amino group of most amino acids is transferred to a-ketoglutarate to from ?

ammonium ion (NH4+)

once glutamate is formed, it is then oxidatively deaminated to yield ?

aminotransferases

enzymes that transfer the amino group from an a-amino to an a-ketoacid

amino groups being incorporated into glutamate

aspartate + a-ketoglutarate —> oxaloacetate + glutamate

alanine + a-ketoglutarate —> pyruvate + glutamate

glutamate dehydrogenase (GDH)

enzyme that oxidatively deaminates glutamate inside the mitochondria to release NH4+

NH4+

when glutamate is oxidatively deaminated by GDH inside the mitochondria, it releases ?

mitochondria

where glutamate is oxidatively deaminated to release NH4+

glutamate dehydrogenase (GDH)

unique because it can use both NAD+/NADH and NADP+/NADPH

serine and threonine

exceptions in that their amino groups can be directly converted into NH4+ instead of first being transferred to a-ketoglutarate

serine dehydratase

threonine dehydratase

enzymes that directly convert the amino groups from serine and threonine into NH4+

peripheral tissues (ex. muscles)

can use branched-chain amino acids as fuel

glucose-alanine cycle

transfers the nitrogen from the branched-chain amino acids in peripheral tissues (muscles) to the liver

nitrogenous compounds

some of the NH4+ formed from the degradation of amino acids is used in the synthesis of ?

aquatic animals release free ammonia

terrestrial species excrete excess NH4+ as urea

birds and reptiles convert excess NH4+ to uric acid

3 different ways animals excrete excess NH4+ depending on the amount of available water

urea cycle

first step (formation of carbamoyl phosphate from ammonia and CO2) takes place in the mitochondria, the rest in the cytoplasm

second amino group of urea comes from amino acid aspartate

takes 4 ATP molecules to synthesize one molecule of urea

aspartate

where the second amino group of urea comes from

4 ATP molecules

amount of ATP molecules needed to synthesize one molecule of urea

acetyl-CoA

acetoacetyl-CoA

pyruvate

a-ketoglutarate

succinyl-CoA

fumarate

oxaloacetate

metabolic intermediates yielded from the carbon skeletons of amino acids being degraded

glucogenic amino acids

amino acids that give rise to succinyl-CoA, pyruvate, a-ketoglutarate, fumarate, and oxaloacetate

glucogenic amino acids

produces intermediates that can serve as precursors to glucose synthesis

succinyl-CoA

pyruvate

a-ketoglutarate

fumarate

oxaloacetate

intermediates produced from glucogenic amino acids

ketogenic amino acids

amino acids that give rise to acetyl-CoA and acetoacetyl-CoA

ketogenic amino acids

produces intermediates that can be used to synthesize fatty acids or ketone bodies

alanine

converted to pyruvate simply by the loss of its amine group

serine

loses both its amine and hydroxyl group in a single step to produce pyruvate

cysteine

converted to pyruvate by loss of its amino group and its SH group

glycine

can be converted to serine, and then to pyruvate

threonine

can be converted to pyruvate through an intermediate

tryptophan

has a 3 carbon main chain, not part of its indole ring, that gives alanine, which is then converted to pyruvate

indole ring is converted to acetyl-CoA and acetoacetyl-CoA by a different pathway

alanine

serine

cysteine

threonine

glycine

tryptophan

C3 family of amino acids that produce pyruvate

asparagine

first deaminated to form aspartate

aspartate

deaminated to form oxaloacetate

asparagine

aspartate

C4 amino acids that produce oxaloacetate

glutamine

proline

arginine

histidine

can all be converted to glutamate and then converted to a-ketoglutarate

C5 amino acids

glutamate

can be converted to a-ketoglutarate by oxidative deamination by glutamate dehydrogenase

valine

isoleucine

methionine

all converge at propionyl-CoA and then converted to succinyl-CoA

the carboxyl groups from all three are lost as CO2

succinyl-CoA

propionyl-CoA is converted to ?

valine and isoleucine

branched chain amino acids that requires a special enzyme complex to form propionyl-CoA

leucine

one of two purely ketogenic amino acids

is deaminated and after several reactions is cleaved to yield acetyl-CoA and acetoacetate that are used to make ketone bodies or fatty acids

acetyl-CoA and acetoacetate

leucine produces ? and ?

lysine

reverse of its biosynthetic pathway to yield acetoacetyl-CoA

tryptophan

yields pyruvate from its main chain, but the indole ring is converted to acetoacetate by the same reactions as in lysine degradation

phenylalanine

begins by being hydroxylated to form tyrosine, then tyrosine forms fumarate and acetoacetate

tyrosine

forms fumarate and acetoacetate

deficiencies in enzymes that breakdown certain amino acids

leads to a number of inherited diseases

phenylketonuria

caused by absence of phenylalanine hydroxylase

phenylalanine hydroxylase

enzyme that converts phenylalanine into tyrosine

phenylketonuria

leads to severe mental retardation

not clear if symptoms are caused by the absence of tyrosine (used to make neurotransmitters) or by excess of phenylalanine or both

diet low in phenylalanine supplemented with tyrosine started at birth

treatment for phenylketonuria