m06

how are dietary proteins digested 2

HCL

• denatures

Pepsin

• secreted by stomach as zymogen (proenzyme), pepsinogen

• active pepsin cleave part of the sequence after being unfolded by HCL to activate

2 main digesstive enzymes

• trypsin (enteropeptidase activates trypsinogen)

• chymotrypsin

acute pancreatitis (2)

• obstruct panc duct = block panc secretions

• zymogens conevrt to active forms inside pancreas = attack panc tissue

cystinuria (3)

• defective transporter for basic amino acids: arginine, cysteine, ornithine, lysine

• ecreted in urine bc cant reabsorbed in kidney

• high cysteine in urine = kidney stone, ureter and bladder stone

2 modes of protein digest in CEDLLS

1. lysosomes

   1. m6P tag

   2. hydrolases in acidic envt degrade, and enzymes that cleave

   3. after being broken down, transport to cytosol for reuse

2. proteasome NOT ORGANELLE

   1. ubiquitin tagging for damaged cytosol and nuclear prots

   2. transfer to proteasome to unfold and remove ubiquitin

   3. clevaed into peptides using ATP

commitment step in catabolism of amino acids (3)

transamination

• a-amino transfer nh3 to a-keto acid that accepts nh3

• aminotransferases uses a-ketoglutarate (always the acceptor) to make lutamine

this enzyme is in cyto of cells

coenzyne for amino transferase

vit b6 as a coenzyne

2 aminotransferase reacions

ALT

• amino group from alanine to a-ketoglutarate = pyruvate and glutamate (nh3 colllector)

AST

• amino group from glutamate to oxaloacetate = aspartae (for urea cycle) and a-ketoglutarate

diagnostic value of aminotransferases (3)

• high in blood (cuz usually intracell) = cell dmg

• liver and non-liver diseases can deelop with thie elevation

• Blood AST and ALT elevated in all liver diseases,

Glutamate dehydrogenase (4)

• remove ammonia from glutamate to get a-ketoglutarate or vice versa

• compartmentalized in liver mito

• can use both NADH and NADPH

• direction dependent on concentrations

• Inhibited by GTP

• Activated by ADP

disposal (oxidative deamnation)

• liver

• glutamate = a-keto + nh3

• NAD+ coenzyme

aa synthesis (2) reductve amination

• make glutamate

• uses NADPH coenzyze

• increased by ADP

• decreased by NADH

muscle tramsport ammonia to liver

1. ammonia + pyruvate = alanine non toxic

2. alanine transaminated in liver to make glutamate

urea substrates (3)

• nh3

• aspartate nitrogen

• Co2 as bicarbonate

CPS 1

• activated by N-acetylglutamate (high argiine when urea production too slow)

hyperammonemia (3)

• high blood level of ammonia

• neurotoxic effect on CNS (tremor, speech slur, vision blur)

• coma and death

proeducts of catabolising carbon skeleetons of aa (5)

for glucose or lipid or energy

• oxaloxacetate

• pyrufate

• fumarate

• acetyl coa

• succinyl coa

4 gluco/ketogenic amino acids

• tyrosine

• isoleucine

• phenyalanine

• tryptophan

branched chain aa catabolism - isoleucine, leucine, valine (3)

• not degrade in liver

• transamination by branched chain aminotransferase to make the a keto enzymes (enz not in liver)

• BCKD catalyzed decarboxylation to yyield the Acetyl Coa derivatives

• transformed to glucogeic or ketogenic precursors

how to synthesize nonessensial aa (3)

• aminotransferase makes a-keto acids and ala, asp, or glutamate

• amidation of glutamate and aspartate to glutamine and asparagine

MSUD (4)

• deficient branched chain a-keto acid dehydrogenase

• 0 thus the branched chain aa and their keto analogs are elevated in plasma and urine

• server metabolic acidosis = maple syrup

• treatment: restrict dietary intake

PKU (3)

• deficient phe hydroxylaze

• phe cant turn into tyr = symptom is elevated in tiss, blood,urine and developmental delay

• early diagnosis, treat with low phe diet

albinism

defect in tyrosine metabolis

• hypopigmentation