Protein metabolism Flashcards
Protein digestion begins where?
stomach
- secreted by chief cells
- hydrolyses 46 amino acids from its N-terminus (autocatyltic reaction) to make pepsin
pepsinogen
- secreted by parietal cells in response to food entering the stomach
- denatures proteins
HCl
chyme
acidic mass as it enters the duodenum
chyme stimulates cells of intestinal mucosa to secrete what into the blood?
secretin and cholecystokinin
stimulates release of bile from gall bladder and digestive enzymes from pancreas
cholecystokinin
stimulates acinar cells of pancreas to release HCO3- rich fluid that neutralizes the acidic chyme as it enters the intestines
secretin
- activated by enteropeptidase
- activates the following:
chymotrypsinogen»chymotrysin
proelastase»elastase
procarboxypeptidases»carboxypeptidases
trypsin (made from trypsinogen by action of enteropeptidase, membrane-anchored)
transport systems of amino acids generally use energy provided by what?
sodium electrochemical gradient
- inappropriate response to alpha-gliadin, found in gluten
- loss of villi, appears flat
symptoms: nutrient dieficiency
Celiac Disease
treatment: gluten-free diet
- inflammatory disease of pancreas
- digestive enzymes are being activated inside the pancreas
- causes mild (abdominal pain) to severe (pancreatic necrosis) symptoms
acute pancreatitis
- defect in large neutral acid transport system, unable to get into the epithelial cells
- same transporter in kidney that is responsible for reabsorption
- exhibit malnutrition and presence of neutral amino acids in urine
Hartnup Disease
treatment: niacin
major site of amino acid degradation during fasting
liver
What enzyme catalyzes the reaction glutamate»alpha-ketoglutarate?
glutamate dehydrogenase
- makes NADH from NAD+
- transfer of ammonium ion
- major route for glycine catabolism
- most active in liver
- major contributor to synthesis of glycine
mitochondrial glycine cleavage system
glycine+THF»N5,N10-methylene THF (NADH is made as well)
*fully reversible
How does the body get glycine?
mostly from the diet, other times from mitochondrial glycine cleavage system
- defect in mitochondrial glycine cleavage system
- present soon after birth
symptoms: lethargy, lack of muscle tone and muscle twitching, may progress to apnea and death
Glycine encephalopathy (aka nonketotic hyperGLYcinemia) - reduction in glycine greatly affects muscles because collagen is mostly made up of glycine
What is the relationship between glucose and alanine?
it’s a way for muscles to get rid of ammonium ions
- in the muscle glucose is converted down to alanine, which then leaves and moves to the liver
- in the liver alanine is converted to pyruvate (transferring ammonium ion) then back to glucose (gluconeogenesis), which gets released and absorbed back by muscle
Where is AST found?
liver, cardiac muscle, skeletal muscle, kidney and several other tissues
Where is ALT found?
mostly liver
Elevation of AST in serum is indicative of what?
inconclusive because it’s found in a lot of muscles, but definitely some sort of organ damage because it’s normally really low in serum
Elevation of ALT in serum is indicative of what?
if it’s just ALT, then it’s also inconclusive, it must be both AST and ALT in serum to rule that it is liver damage as both are found in the liver
What amino acid is required to facilitate new tissue growth thus considered as essential during periods of growth and is a cause for pressure ulcers in the elderly population?
arginine
- result in the inability to convert Phe»Tyr
- deficiency in either Phe hydroxylase or DHBtn Redutase
- Phe is instead converted to phenylpyruvate
Symptoms: intellectual disability, recurrent seizures, hypopigmentation, eczematous skin rashes
Phenylketonuria (PKU)
Treatment: Phe-free diet, lifelong monitoring
- taken up by intrinsic factor produced by stomach
- absorption occurs in ileum
- once absorbed, binds to transcobalamin (transport protein)
- liver stores for up to 6 years
Dietary B12
lack of B12 in diet (such in long term strict vegans)
actual B12 deficiency
inability to absorb B12 or metabolize it
functional B12 deficiency
What does glucogenic mean?
amino acids thatcan be converted to OAA to start gluconeogenesis
What does ketogenic mean?
amino acids that can be converted to acetyl-CoA or acetoacetyl-CoA
- Lysine and Leucine are ketogenic only (both Ls of PVT TIM HALL)
- everything else is glucogenic
How is glutamate dehydrogenase regulated?
- high cellular energy (increased GTP and NADH) inhibits it
- low cellular energy (increased ADP) activates it
- mutant forms of glutamate dehydrogenase that are insensitive to inhibition by GTP
- inability to inhibit glutamate dehydrogenase (constitutively on)
Familial Hyperinsulinemic Hypoglycemia Type 6
NADH constantly being produced»ETS»ATP»insulin» hyperinsulinemic and hypoglycemia
- metabolic end product
- high affinity for calcium ions
- tend to precipitate in kidney tubules leading to kidney stone formation
oxalate (oxidized from glyoxalate which is transminated from glycine)
The co-factor THBtn (tetrahydrobiopterin) is oxidized to DHBtn by what enzyme and what is the reducing equivalent that is used?
DHBtn reductase, NADH
What can be used to synthesize propionyl-CoA?
Thr, Met, Val, Ile and odd-chain FAs
What enzyme converts propionyl-CoA to D-methylmalonyl-CoA?
propionyl-CoA carboxylase
Back up of propionyl-CoA leads to what condition and is caused by what defective enzyme?
propionic acidemia, caused by defective propionyl-CoA carboxylase
Back up of D-methylmalonyl-CoA leads to what condition and is caused by what defective enzyme?
D-methylmalonic aciduria, caused by defects in the enzyme racemase that converts D form to L form of methylmalonyl-CoA
Back up of L-methylmalonyl-CoA leads to what condition and is caused by what?
B12 deficiency and defective mutase that converts L-methylmalonyl-CoA to succinyl-CoA
What disease is associated with lack of intrinsic factor?
pernicious anemia, inability to absorb B12
Why is THF important?
required for the synthesis of purine and thymidine (RNA and DNA synthesis)
accumulation of N5-methyl-THF
B12 deficiency
Explain the presentation of megablastic anemia
B12 deficiency leads to the inability to convert N5-methyl-THF back to THF, which is required for synthesis of RNA and DNA. This leads to lack of cell division, lack of DNA replication. Both of which are important for RBCs because they are constantly being made. This leads to the cells attempting the go through the cell cycle and just leading to the cells getting bigger but without dividing.
Symptoms: dislocation of optic lens, osteoporosis, lengthening and thinning of long bones, thromboembolism, and intellectual disability (very wide spectrum)
most often caused by mutations in the gene that encodes cystathionine beta-synthase (CBS) **Think CBS television logo and that it looks like an eye (optic lens problem)
- presence of branched-chain alpha-ketoacids in urine
- poor feeding, vomiting, slow or irregular breathing, ketoacids, hypoglycemia, and neurological dysfunction
Maple Syrup Urine Disease (MSUD)
- BCKDH defect
Treatment: diet restriction with reduced BCAAs (can’t completely get rid of because they are essential amino acids)
- defective tyrosine aminotransferase
Symptoms: painful skin lesions on the palms of the hand and the soles of the feet, keratitis, photphobia
Tyrosinemia II
- easily recognized because urine will turn black upon exposure to air
- buildup of homogentisate due to defect in homogentisate oxidase
- oxidized products of homogentisate will cause pigmentaion or ochronosis, or connective tissue and arthritis
- pain due to spine and joint destruction by age 20 or 30
Alkaptonuria
Treatment: reduction of homogentisate
Nitisinone - inhibitor of the enzyme that produces homogentisate (hydroxyphenylpyruvate hydroxylase)
- maleylacetoacetate and fumarylacetoacetate accumulate and are converted to sccinylacetoacetate, which carboxylates to form succinylacetone
- succinylacetone potent inhibitor of heme synthesis
Tyrosinemia I
