protein metabolism Flashcards
Collagen is the most abundant protein in human body that forms a triple-stranded helix, which is comprised of both ___________ and ___________
hydroxyproline (Hyp) and hydroxylysine (Hyl)
Hydroxyproline serves what function in collagen
used in collagen for H-bonding that increases collagen strength
_____ converts Proline to Hydroxyproline
Prolyl hydroxylase
what function does hydroxylysine (Hyl) serve in collagen?
used in collagen for interchain cross-links
________ converts Lysine to Hydroxylysine
Lysyl hydroxylase
____________ and _________ rely on Vit-C (ascorbate) as coenzyme, thus, lack of Vit-C leads to Scurvy (i.e. reduced collagen strength).
Prolyl hydroxylase,
Lysyl hydroxylase
__________________ converts Glutamate to g-Carboxyglutamate (Gla), which is Vit-K dependent.
G-glytamyl carboxylase
Describe the Ubiquitin-proteasome system, a type of intracellular protein breakdown pathway.
ATP dependent that is used to cross-link protein to ubiquitin. Ubiquitinated proteins are then sequestered to the proteasome (i.e. a giant cellular trashcan that has proteolytic activity to break down proteins).
describe the Lysosomal pathway, which is a type of intracellular protein breakdown pathway.
ATP independent that is used primarily to “engulf” extracellular proteins (or even live pathogens). Proteins are broken down by acid hydrolysis and other lysosomal proteins (i.e. cathepsins).
what are Aminotransferases?
enzymes that transfer amino groups (nitrogen movers)
Ultimately for protein degradation, aminotransferases move nitrogen to _____ and _______ which are the molecules that carry nitrogen into the Urea Cycle where ultimately the nitrogen winds up on urea which is excreted in the urine.
aspartic acid (Asp), ammonia
What are two entry points for Nitrogen in the urea cycle:
1) Apartate.
2) Free ammonia (incorporated into carbamoyl phosphate)
_______ is an allosteric activator of Carbamoyl phosphate synthetase I.
N-acetylglutamate
______ is an activator of N-acetylglutamate synthase, which catalyzes the following reaction:
acetyl CoA + glutamate to N-acetylglutamate
Arginine
Most tissues use ________ to convert glutamate to glutamine for transport to the liver (to enter the urea cycle).
glutamine synthetase
_____ converts arginine to citrulline to produce NO, an important molecule used as a neurotransmitter and vasodilator
NO synthase
Branched Chain Amino Acids include _________
leucine, valine, and isoleucine
what is Maple Syrup Urine Disease (MSUD)
Occurs when branched-chain alpha-ketoacid dehydrogenase complex is deficient and there is consequently a buildup of the alpha-keto acids in urine (“sweet smelling”).
________ is used to make T4 (prohormone) that is converted to T3 (hormone).
Tyrosine
Thyroid stimulating hormone (TSH): Stimulates _____ uptake and stimulates release of T4 andT3.
iodide (I-)
What does Thyroid peroxidase do?:
Oxidizes iodide (I-) to (I2).
what is Thyroglobulin (Tg)
Contains Tyr residues iodinated to form T4 andT3.
what does Thyroxin binding globulin (TBG) do?
Transports T4 andT3.
Creatine phosphate and ornithine are derived from ______
Arginine
which 2 amino acids contain sulfur
methionine and cystiene
what is Hyperhomocysteinemia? .
elevated levels of homocysteine cause multiple problems that include cardiovascular disease
what can cause Hyperhomocysteinemia?
Results from low levels of folate, B6, & B12 (vascular disease)
What is Homocystinuria: . Leads to mental retardation, osteoporosis, & vascular disease
results from defect in cystathionine-b-synthase (CBS), so that homocysteine cannot be converted to cystathionine (and eventually cysteine).
What is the presentation of Homocystinuria
mental retardation, osteoporosis, & vascular disease.
What is Cysteinuria?
Due to a defect in the transporter of cysteine (& Ornithine, Lysine, Arginine) that leads to crystallization in urea -> kidney stones (renal failure)
how do you treat Cysteinuria
acetazolamide (makes cysteine more soluble)
what are the 3 functions of Glutathione (GSH)
i) thiol acts as redox buffer (“SH buffer”) to maintain proteins in their reduced forms (i.e. intracellular proteins) and regulate activity (i.e. enzymes)
ii) Cofactor for several enzymes (i.e. Glutathione transferase, GST).
iii) Reduce hydrogen peroxide (H2O2) to water and general protection against ROS (radical oxidizing species).
Trp is used to produce
serotonin (neurotransmitter), melatonin (hormone), and niacin (energy).
Trp is metabolized to ___________ .
pyruvate or acetyl-CoA
Phe, Tyr are metabolized to _________
fumarate or acetoacetate
Phe is hydroxylated by phenylalanine hydroxylase to produce ______ using ______ cofactor
Tyr,
BH4
Tyr is hydroxylated by tyrosine hydroxylase to produce DOPA using BH4, which is subsequently metabolized to: ________
1) Catecholamines, which include DOPA, dopamine, norepinephrine, epinephrine.
2) Melanin, which is a pigment produced as a complex combination of several molecules derived from Tyrosine metabolism.
what is Phenylketonuria (PKU)?
A defect in phenylalanine hydroxylase that leads to build-up of alternative byproducts (phenylactate, phenylacetate, and phenylpyruvate).
Porphyrins such as Heme are cyclic molecules made of ________ primarily produced in liver
4x pyroles
Porphyrins bind ________.
Fe2+ (iron)
________ are the general term for diseases in porphyrin synthesis
Porphyrias
Lead inhibits two enzymes in porphyrin synthesis ____________ ”lead poisining”.
(delta-Aminolevulinate dehydratase, ferrochelatase)
