MTC exam II week I Flashcards
How does dna replication happen in a mitochondrion
begins at Oh (origin of replication for the heavy strand) with binding of mitochondrial RNA primer. we see L strand displacement and clockwise replication. RNA primer is synthesized by mitochondrial RNA pol. we see growth of the D loop. When the H strand replication has proceede dto around 8 o’clock, L strand replication begins with the binding of the 2nd RNA primer in a coungerclockwise direction. topoisomerases allow for recoil of the mitrochndrial DNA
What are the 2 non-coding regions in the control regions of mitochondrial DNA?
hypervariable regions I and II
What are some things that pyruvate can become?
lactate, alanine, acetyl CoA and oxaloacetate. maybe DHAP>
What is an example of a nuclear-based mitochondrial defect that is not autosomal recessive?
most common pyruvate dehydrogenase (to acetyl CoA) is X-linked dominant
Leber’s Hereditary Optic Nueropathy (LHON)
mitochondrial disease
usually complex I mutation
central vision loss due to retinal degradation; most common among men
heteroplasmy rare
MELAS
mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
progressive neurodegenerative diseases involving chemical stroke, lactic acidosis, and myopathy
tRNA leu gene is missing/defective
heteroplasmy common
MERRF
myoclonic epilepsy with ragged red fibers
myotonic seizures, dementia, ataxia, ragged red fibers
tRNAlys gene
heteroplasmy
KSS and CPEO
diseases seen before 20 yrs of age
opthalmoplegia, ptosis, atypical retinitis pigmentosa, ragged-red fibers. involve contiguous deletion of part of the mitochondrial tRNA
kearns-sayre syndrome and chronic progressive external ophthalmoplegia
NARP and Leigh diseases
ataxias. mutations in the ATP6 gene
Where does fatty acid synthesis occur (organ and organelle)? What five factors are required?
fatty acid synthesis occurs in the cytosol of the hepatocytes. it requires acetyl CoA, ATP, CO2/bicarb, biotin, pantothenic acid, and NADPH
What are happens in the first stage of fatty acid synthesis? What enzyme catalyzes this reaction?
acetyl CoA +CO2 + ATP forms malonyl CoA (which has 3 C). this reaction is catalyzed by acetyl CoA carboxylase and a biotin cofactor
What enzyme is inhibited by malonyl CoA
CPTI (carnitine palmitol transferase I, which is involved in fatty acid degredation)
acetyl CoA carboxylase
catalyzes the first reaction of fatty acid synthesis (CO2 + acetyl CoA yield malonyl CoA). Requires biotin. ping-pong
What happens in the 2nd stage of fatty acid synthesis? What is the enzyme?
you start with acetyl CoA and add 2 carbons from malonyl CoA at a time. Enzyme is fatty acid synthase
fatty acid synthesase
cofactors: 4/phosphopantethein from pantothenic acid. catalyzes 4 different rxns and has two major binding sites.
mechanism of action: fatty acid synthetase
sites A and B alternate as attachemnt sites for growing fatty acid chaine.
- Acetyl group attaches to the sulfhydryl of the A/KS site.
- malonyl attaches to the B/ACP site
- acetyl group attached to KS displaces the terminal carbonyl of the malonyl group and CO2 is released. The 4 C chain on the ACP site is called beta-ketobutyryl ACP
- betaketobutyryl ACP swings around and undergoes reduction (uses NADPH), hydration, and reduction again (another NADPH)
- growing chain is transfered back to the the KS subunit
palmitoyl thioesterase
detaches the palmitic acid from the fatty acid synthase enzyme
What are the energetic costs of palmitate synthesis?
7 ATP in the first step
14 NADPH in the second step
8 acetyl CoA
you only get 108 ATP from palmitate, even though it costs about 200 ATP to make
glycerol kinase
found in the liver only. converts glycerol and ATP into glycerol 3 phosphate
glycerol-3-phosphate dehydrogenase
found in adipose and periphery. converts DHAP and NADH into glycerol 3 p for triacylclycerol synthesis in the periphery
acyl CoA synthase
turns fatty acids and ATP into activated fatty acids fro triacylglyceride synthesis
acyl transferase
adds activated fatty acids to glycerol-3-phosphate at C1 and C2 positions. if we stop there, we have phospholipids)