Term
| Where are amino acids converted to urea? |
|
Definition
|
|
Term
| Where does protein digestion begin, and where does it end? |
|
Definition
|
|
Term
| What are zymogens, and how are they activated? |
|
Definition
| Inactive proteases; activated by protease cascade |
|
|
Term
| What secretes HCl in the stomach and what are the two main actions of HCl? |
|
Definition
| Parietal cells; denature proteins by killing hydrogen bonds and activate pepsinogen to become pepsin |
|
|
Term
| What enzymes are secreted by the small intestine and what do they do? |
|
Definition
| Enteropeptidases and aminopeptidases; act within the brush border to digest proteins to free amino acids |
|
|
Term
| What converts trypsinogen to trypsin? |
|
Definition
| Enteropeptidase in small intestine |
|
|
Term
| Name 3 zymogens activated by Trypsin: |
|
Definition
Chymotrysinogen to Chymotrypsin
Proelastase to Elastase
Procarboxypeptidases to Carboxypeptidases |
|
|
Term
| Where on the protein does endoprotease cleave? |
|
Definition
|
|
Term
| Where on the protein does aminopeptidase cleave? |
|
Definition
| At the end- no specificity for amino acids- N-terminus |
|
|
Term
| What are the 3 routes of amino acid transport into cells? |
|
Definition
Secondary active transport- Na dependent MOST COMMON
Facilitated Diffusion
Glutamyl cycle |
|
|
Term
| What is the destination of the amino acids in secondary active Na dependent transport? |
|
Definition
| From lumen of small intestine to intestinal epithelium |
|
|
Term
| What is the destination of the amino acids in facilitated diffusion? |
|
Definition
| From intestinal epithelial cells to portal circulation |
|
|
Term
| What is the final result of the glutamyl cycle? |
|
Definition
Transports amino acids form intestinal epithelium to portal circulation
MAKES GLUTATHIONE |
|
|
Term
| What is the daily dietary recommendation of protein for the average 70Kg man? |
|
Definition
|
|
Term
|
Definition
Defective transporter of essential neutral amino acids in intestines and kidney- most get peed out
-Photosensitivity, rash, ataxia and neuropsych symptoms |
|
|
Term
|
Definition
Defective transporter of dibasic amino acids in intestines and kidneys- they get peed out
-kidney stones of cysteine |
|
|
Term
| What two systems are in place to degrade proteins back into amino acids? |
|
Definition
| Lysosomes and Proteasomes |
|
|
Term
| What are the primary proteases? |
|
Definition
|
|
Term
| What tags proteins in the proteasome for degradation? |
|
Definition
|
|
Term
| What is defective in Cystic Fibrosis? |
|
Definition
|
|
Term
| What is the effect of Cystic Fibrosis in the pancreas? |
|
Definition
Drying and thickening of the pancreatic secretions causing CLOGGED PANCREATIC DUCTS and DECREASED DIGESTION OF PROTEINS AND LIPIDS
(No proteases or amylases) |
|
|
Term
| What are the symptoms of Cystic Fibrosis? |
|
Definition
Listlessness, irritability, tiring easily
GLISTENING, BULKY, FOUL-SMELLING STOOL
Symptoms caused by lack of lipases and proteases from pancreas |
|
|
Term
| How is Cystic Fibrosis treated? |
|
Definition
| Administer enteric coated microspheres of pancreatic enzymes to replace those that are missing |
|
|
Term
| What type of patient would present with a positive nitrogen balance? |
|
Definition
| More N in than out: growing children, pregnant women, body builders |
|
|
Term
| What type of patient would present with a negative nitrogen balance? |
|
Definition
| More nitrogen lost: illness, surgery, stress (epinephrine and cortisal) |
|
|
Term
|
Definition
Patient has calories but no protein
EDEMA |
|
|
Term
|
Definition
Deficient in protein and calories
WASTING |
|
|
Term
| What are the primary amino acids released from muscle protein in the fasting state? |
|
Definition
|
|
Term
| What happens in the first step of amino acid metabolism? |
|
Definition
| AAs are stripped of their amino groups to yield glutamate and Alpha keto acid |
|
|
Term
| What are the two fates of glutamate in amino acid metabolism? |
|
Definition
Generate ammonia through oxidative deamination (GDH)
Generate aspartate from oxaloacetate thorugh more transamination |
|
|
Term
| What are the 3 components to generating urea? |
|
Definition
| CO2, Ammonia, Aspartate Amino group |
|
|
Term
| What enzymes remove the amino group from amino acids and where does it get transferred to? |
|
Definition
| Transaminases (aminotransferases); an alpha keto acid |
|
|
Term
| What is the role of Vitamin B6 (Pyridoxal phosphate)? |
|
Definition
| A cofactor in transamination (reversible); cycles between pyridoxal and pyridoxamine forms |
|
|
Term
How is amino acid nitrogen released?
What are the two processes? |
|
Definition
AA nitrogen is released as ammonia (NH3)
-deamiNation- removal of amine group
-deamiDation- removal of amide group |
|
|
Term
| What is the role of glutamate in amino acid metabolism? |
|
Definition
-feeds things into urea cycle
-collects nitrogen from other amino acids by transaminase reactions
-can be released as NH4+ or transferred to OAA to form aspartate and enter the urea cycle |
|
|
Term
| What is the function of Glutamate Dehydrogenase (GDH)? |
|
Definition
-Yields lots of ammonia
-deaminates glutamate to NH4+ and alpha ketoglutarate
NAD+ or NADP+ are required (oxidative)
REVERSIBLE |
|
|
Term
| What is the major waste form of nitrogen? |
|
Definition
UREA-
minor: uric acid, creatinine, NH4+ |
|
|
Term
Where is urea produced?
Where is it transported to? |
|
Definition
|
|
Term
| What catalyzes the generation of carbamoyl phosphate in the first reaction of the urea cycle? |
|
Definition
| Carbamoyl phosphate synthetase I |
|
|
Term
| What are the 8 intermediates/products of the urea cycle? |
|
Definition
Old Codgers Can Always Accumulate Feces And Urine
-Carbamoyl phosphate
-Ornithine
-Citrulline
-Aspartate
-Argininosuccinate
-Fumarate
-Arginine
-Urea |
|
|
Term
| Where does the urea cycle occur? |
|
Definition
First two steps in mitochondria
Rest occurs in cytosol |
|
|
Term
| What is the nitrogen carrier that is regenerated in the urea cycle? |
|
Definition
|
|
Term
| How does high ammonia production affect the Urea Cycle? |
|
Definition
| High Ammonia stimulates the urea cycle to feed forward |
|
|
Term
| How does a protein diet or fasting stimulate the urea cycle? |
|
Definition
| They stimulate the urea cycle and induce urea cycle enzymes |
|
|
Term
| How does N-acetylglutamate (NAG) affect the urea cycle? |
|
Definition
| It is a positive allosteric effector of carbamoyl phosphate synthetase I |
|
|
Term
| Where are the two (different) amino groups in the urea cycle derived from? |
|
Definition
1 is from ammonia
1 is from aspartate |
|
|
Term
| What is the "central molecule in nitrogen metabolism"? |
|
Definition
|
|
Term
| What is the most common urea cycle deficiency? |
|
Definition
Ornithine Transcarbamoylase Deficiency
X-linked, males |
|
|
Term
| What enzyme, present in the kidneys, works to maintain the body's acid-base balance and can help excrete ammonia? |
|
Definition
|
|
Term
| What is the enzyme used by bacteria in the intestines to release Ammonia and CO2? |
|
Definition
|
|
Term
| What are the symptoms of Hyperammonemia? |
|
Definition
elevated blood ammonia
-tremors, slurred speech, blurred vision
-coma, death |
|
|
Term
| What are the causes of acquired hyperammonemia? |
|
Definition
Alcoholism, hepatitis, biliary obstruction
-if access to liver is prevented, blood is shunted directly to the circulation |
|
|
Term
| What causes hereditary hyperammonemia? |
|
Definition
Defects in the enzymes of the urea cycle
-occurs within 1 week of birth
-causes retardation |
|
|
Term
| What is found in the blood plasma in the highest concentration of any AA? |
|
Definition
|
|
Term
| What is the major ammonia removal mechanism in the brain? |
|
Definition
|
|
Term
| How is circulating glutamine removed by the kidneys, and what do they do with it? |
|
Definition
| Renal Glutaminase; Used as a source of energy |
|
|
Term
| What two amino acids are essential only for the growth phase of children? |
|
Definition
|
|
Term
| What amino acid requires adequate amounts of phenylalanine to make? |
|
Definition
|
|
Term
| What amino acid requires methionine for its sulfur atom? |
|
Definition
|
|
Term
| What are the essential amino acids? |
|
Definition
PVT TIM HALL (REVIEW)
Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine |
|
|
Term
How many ATP are consumed in the synthesis of serine?
How many NADH are produced/consumed? |
|
Definition
1 ATP is used
1 NADP is produced and 1 NADP is used |
|
|
Term
| What is the consequence of excess glycine? |
|
Definition
| Glycine converts to oxalate and makes STONES |
|
|
Term
| What is special about the stereochemistry of Glycine? |
|
Definition
| Since there are 2 H's on teh terminal carbon, D or L configurations are both possible, so we must used D-amino acid oxidase to control the production of ONLY D isomers |
|
|
Term
| What is the usefulness of oxalate and where does it go? |
|
Definition
| Oxalate is useless, it precipitates with Ca and goes into the urine |
|
|
Term
| What are the two KETOGENIC amino acids and what are they converted to? |
|
Definition
| Leucine and Lysine; acetyl CoA or acetoacetate |
|
|
Term
| What are the problems with errors in Methionine metabolism? |
|
Definition
| Homocystinuria; cystathioninuria |
|
|
Term
| What are the problems with errors in the metabolism of branched chain amino acids? (Val, Leu, Ile) |
|
Definition
| Maple syrup urine disease |
|
|
Term
| What problems are associated with errors in phenylalanine metabolism? |
|
Definition
| Phenylketonuria, alcaptonuria, tyrosinemia |
|
|
Term
| What vitamin is required for metabolism of homocysteine in the breakdown of methionine? |
|
Definition
| B12, which remethylates it and converts it back to methionine |
|
|
Term
| What vitamin is required to provide the sulfur group for cysteine synthesis from homocysteine? |
|
Definition
|
|
Term
| What is the most common type of homocysteinuria, and what causes it? |
|
Definition
| Secondary; poor nutrition in adults- deficiency in B6, B12, or Folic Acid |
|
|
Term
| Homocysteinuria (excess homocysteine in the urine) is associated with what clinical problem? |
|
Definition
| Increased risk for CARDIOVASCULAR DISEASE |
|
|
Term
| What are the 3 main problems associated with Homocysteinuria? |
|
Definition
Atherosclerosis- peroxidation of LDLs leading to deposits on arterial walls
Defective collagen synthesis- improper cross linking LENS OF EYE
Brain seizures and retardation- trapping of adenosine (a brain depressant) |
|
|
Term
| What are the two main causes of Cystathioninuria? |
|
Definition
| Defect in cystathionase or deficiency in Vitamin B6 |
|
|
Term
What is the difference between:
Cystathioninuria
Cystinuria
Cystinosis |
|
Definition
Cystathioninuria- cystathionine in urine
Cystinuria- defective cystine transporter in kidney and intestines
Cystinosis- defective cystine transporter in lysosomal membranes (crystals in lysosomes causing renal failure) |
|
|
Term
| Name 3 branched chain amino acids |
|
Definition
| Valine, Leucine, Isoleucine |
|
|
Term
| What is the main clinical condition that causes an inability to break down branched chain amino acids? |
|
Definition
| ALCOHOLISM- thiamine deficiency- accumulation of Alpha Ketoacids in blood leads to ketoacidosis |
|
|
Term
| The transamination reaction that deaminates branched chain amino acids into alpha keto-acids requires what vitamin? |
|
Definition
|
|
Term
| What enzyme is deficient in Maple Syrup Urine Disease, and what is the most obvious clinical presentation? |
|
Definition
| Alpha Keto Dehydrogenase; distinctive smell to the urine |
|
|
Term
| What are the consequences of Maple Syrup Urine disease? |
|
Definition
| Accumulation of alpha keto-acids leading to ketoacidosis, retardation, and possibly death |
|
|
Term
| What amino acid metabolism issue is linked to albinism? |
|
Definition
| Impaired conversion of tyrosine to melanin |
|
|
Term
| What enzyme is deficient in Phenylketonuria and what causes the deficiency? |
|
Definition
| Phenylalanine hydroxylase- from mutations; deficiency in BH4 synthesis; deficiency in BH4 reductase activity |
|
|
Term
| What is the BIGGEST problem with Phenylketonuria? |
|
Definition
| Phenylalanine and phenylketones accumulate leading to NEUROTOXICITY AND RETARDATION |
|
|
Term
| Why does PKU cause mental and neurotoxicity problems? |
|
Definition
Accumulation of phenylalanine and phenylketones inhibits neural uptake of tyrosine and tryptophan, which are neurotransmitter substrates
INHIBITS MYELINATION |
|
|
Term
| What enzyme is defective in Alcaptonuria and what are the two clinical symptoms? |
|
Definition
| Homogentisate oxidase; BLACK URINE and arthritis |
|
|
Term
| What is the most severe consequence of tyrosinemia? |
|
Definition
| Liver failure and early death- Tyrosine and its subsequent metabolites are very hard on the liver |
|
|
Term
| What is the name of the ring structure bound to Fe2 in the heme, and from what is it synthesized? |
|
Definition
Porphyrin; GLYCINE AND SUCCINATE
GLYCINE AND SUCCINATE
GLYCINE AND SUCCINATE
GLYCINE AND SUCCINATE
;) |
|
|
Term
| What are the (often misdiagnosed) symptoms of Porphyrias? |
|
Definition
| Insanity, abdominal pain, discolored urine, photosensitivity |
|
|
Term
| What is the isomeric form of the finalized ring of heme? |
|
Definition
| Type III, which is inverted from Type I |
|
|
Term
| How is bilirubin transported to the liver? |
|
Definition
|
|
Term
| What type of poisoning leads to interference with heme synthesis? |
|
Definition
|
|
Term
| Where does heme degradation to bilirubin occur? |
|
Definition
| Macrophages of the reticuloendothelial system (aged RBCs) and in hematomas |
|
|
Term
| What are 2 principle causes of jaundice? |
|
Definition
(elevated bilirubin)-
-Excess Production- as in hemolytic anemia
-Decreased Excretion- as in liver disease, transport defects |
|
|
Term
| By what process is bilirubin conjugated and where is conjugated bilirubin excreted? |
|
Definition
|
|
Term
| What is the difference between Indirect and Direct Bilirubin? |
|
Definition
Indirect Bilirubin- unconjugated, from the breakdown of heme in the spleen- NOT WATER SOLUBLE so carried on albumin
Direct Bilirubin- after bilirubin is conjugated with glucuronic acid in the liver it becomes WATER SOLUBLE
(note there is some unconjugated bilirubin on albumin mixed in with direct bilirubin as it gets excreted in the bile) |
|
|
Term
| What is the normal amount of bilirubin in the urine? |
|
Definition
| NONE- if present there is a problem |
|
|
Term
| What is the main role of adding glucaronic acid to compounds? |
|
Definition
| Improve solubility and secretion |
|
|
Term
| What is the only bilirubin conjugating form from the UGT gene family? |
|
Definition
|
|
Term
| What is the laboratory presentation of Type II Crigler-Najjar? |
|
Definition
Elevated UNCONJUGATED bilirubin
(defective UGT so no conjugation) |
|
|
Term
| What is the difference between Type I and Type II Crigler-Najjar syndrome? |
|
Definition
In Type I there is NO UGT1A1 activity;
In Type II there is VERY LOW UGT1A1 activity |
|
|
Term
| What is Gilbert's syndrome? |
|
Definition
| Very Mild unconjugated hyperbilirubinemia |
|
|
Term
| What drugs should be given with caution to patients with Gilbert's syndrome? |
|
Definition
HIV protease inhibitors; cancer drugs
-both known to inhibit UGT1A1 which is already hurting |
|
|
Term
| What is Dubin-Johnson Syndrome? |
|
Definition
Excess conjugated bilirubin
Defect in transport of conjugated bili into bile
Diagnostic- Urinary Coproporphyrin Pattern
LIVER GROSSLY BLACK
AVOID ESTROGENS |
|
|
