MSK 1.1 Midterm

what is the protein path for nitrogen metabolism?

ingested —> stomach + SI —> skeletal muscle —> liver —> kidney —> excretion

what happens to nitrogen in the stomach + SI?

hydrolyzed to amino acids

how is nitrogen transferred from skeletal muscle —> liver?

• turned into alanine and glutamine via transamination + aminotransferase

• non- toxic ammonia carriers

what is alanine used for?

used by muscle to transfer nitrogen to liver

what is glutamine used for?

transfers nitrogen to liver for excretion

how is nitrogen sent from liver —> kidney?

urea cycle

how does hyperammonia occur?

• Ala or Glu can’t accept NH3 —> asterixis (hand flap)

• excess nitrogen NOT converted to urea

when does negative nitrogen balance occur?

• illness

• starvation: protein breakdown releases nitrogen —> excrete

enzyme markers for skeletal muscle damage

• AST + CK

• ALK PHOS, gamma-GT

enzyme markers for liver damage?

AST + ALT

enzyme markers for kidney damage?

BUN + creatine

skeletal muscle metabolism: Arg Path

Arg + Gly —> creatine —> ADP + creatine-Phos —> ATP + creatine

what does creatine kinase do?

• ADP + creatine-Phos —> ATP + creatine

• reversible

what is function of creatine?

• made in kidney

• storage fuel in muscle

what are the 4 sources of energy produced by Arg path?

• ATP (1-2 sec)

• phosphocreatine transfers phosphate —> ADP

• glycolysis (1 min), anaerobic

• ox phos (hrs), aerobic

skeletal muscle metabolism: NO path

• uses cGMP signal —> EDRF (NO)

what does EDRF signal result in?

• smooth muscle relaxant —> stops myosin

• vasodilation: dec Ca2+ —> dec BP

• NT uses phosphodiesterase to hydrolyze cGMP

• dec blood coagulation + phagocytosis

BCAA pathways characteristics

• catabolized in skeletal muscle

• can’t be direct substrate for beta oxidation

Ile + Val path

Ile or Val or allo-Ile —> long ketoacid —> shorter ketoacid —> PPC —> MMC —> succinyl coa

what does transamination do?

• starting substrate —> long ketoacid

• glutamine carries amine to urea cycle

what does BC ketoacid dehydrogenase do?

• cofactor B1

• long ketoacid —> shorter ketoacid

Maple Syrup Urine Disease

• defective BC ketoacid dehydrogenase + B1

• labs: BCAA, allo- Ile

• symptoms: cerebral edema, sweet urine, ketosis, hypotonia

what is the function of the 2 carbon removal?

• shorter ketoacid —> propionyl coa (organic acid)

• like beta ox

what is the function of propionyl coa carboxylase?

• cofactor B7

• propionyl coa —> MM coa

MM CoA Acidemia

• defective MMC mutase + B12

• labs: MMC acid + ketone in urine, hyperammonia +ketoacidosis

• symptoms: hypotonia, hepatomegaly, thrombopenia, renal/heart failure

BCAA path: Leu

• only converted to ketogenic substrates

• Leu —> long ketoacid —> isovaleric coa —> shorter skeleton —> acetoacetate

what is the function of transamination?

• Leu —> long ketoacid

• NH3 side product —> urea cycle via Glu

what is the function of BC ketoacid dehydrogenase?

long ketoacid —> isovaleric acid (organic acid)

Isovaleric Acidemia

• deficiency in isovaleric dehydrogenase

• labs: isovaleric acid /coa in urine

• symptoms: vomit, sweaty feet odor, lethargy, poor feeding

propionyl coa carboxylase deficiency

• more severe than isovaleric acidemia

• deficiency in PCC + B7

• labs: propionic acid + ketones in urine

• symptoms: VOMIT, encephalopathy, infection, cardiomyopathy

what does VOMIT stand for in PCC deficiency?

dec Val, OCFA, Met, Ile, Thr

BCAA path: Met + Cys

• Ala, Gly, Ser, Thr

• catabolic —> Met

• anabolic —> B12, B9

catabolic pathway

• Met —> SAM —> homocysteine-SH —> cysthionine

• makes both propionyl coa + cys-SH

what does SAM produce?

phospholipids, DNA, NT

what does cysthionine beta synthase do?

• cofactor B6

• uses Ser-OH

• homocysteine-SH —> cysthionine

cysthionine products

• cofactor B6 —> Cys-SH

• propionyl coa

anabolic: B12 cycle

• transfers 1 carbon unit

• homocysteine —> Met via Met synthase +B12-CH3

• MM coa —> succinyl coa via MM coa mutase

deficiency in B12

• pernicious anemia, paresthesia, ataxia, memory loss

• inc MM acid, inc homocysteine

anabolic: B9 cycle

folate —> FH2 —> FH4 —> FH4 methylene —> FH4-CH3

what does a folate deficiency cause?

dec DNA synthesis —> macrocytic anemia