Metabolism Flashcards
fuel preferences of liver, adipose, skeletal muscle, heart, brain
liver- FAs, glucose, AAs adipose tissue- FAs skeletal muscle- FAs (rest), glucose (exercise) heart muscle- FAs brain- glucose, ketone bodies
what is the range we keep blood glucose within?
60-110 mg/mL
low- neurological problems, high- vasculature, nerves, kidneys, organs, T2DM
pathways during fed state stimulated by insulin
glycogenesis, glycolysis (lactate,pyruvate-CAC)
pathways during fasting state stimulated by glycogen & epinephrine
glycogenolysis, gluconeogenesis (non-carb source for glucose)
krebs cycle mnemonic
can i keep selling sex for money officer
citrate, isocitate, alpha-kg, succinyl coa, succinate, fumerate, malate, oxaloacetate
enzyme of pentose phosphate pathway, purpose
glucose 6 phosphate dehydrogenase
- regenerates NADPH, DNA/RNA synthesis
- deficiency causes hemolytic anemia through increase in oxidized glutathione (ROS)
4 key enzymes for reversing glycolysis
pyruvate carboxylase, PEP carboxykinase, fructose 1,6 bisphophatase, glucose 6 phosphatase
3 key enzymes of glycolysis
hexokinase/glucokinase (invest ATP)
PFK1 (invest ATP)
pyruvate kinase
hexokinase vs glucokinase
hexokinase- all cell types, higher affinity to glucose, low km
glucokinase- liver and pancreas, translocated (induced by insulin) between nucleus (inactive- f6p) and cytosol (active), high km, low affinity
the activity of PFK 1 is regulated by
the product of pfk-2= fructose 6 bisphosphatase
pyruvate kinase does what - stimulated/inhibited by
converts PEP to pyruvate
stimulated by insulin, inhibited by glucagon/epi/ATP
PDH does what
pyruvate to acetyl COA
requires B vitamins
how can NAD+ be regenerated ; what does a lack of NADH cause?
lactate dehydrogenase
- converts pyruvate to lactate
- increased NADH increases lactate formation
- need NAD+ to go from glyceraldehyde 3 phosphate to 1,3 bisphosphogycerate
- have exercise intolerance
what does ethanol (alcohol) do?
changes NADH/NAD ratio (increases it); converts pyruvate/oxaloacetate to lactate/malate; causes hypoglycemia
fates of pyruvate
alanine
oxaloacetate
lactate
acetyl CoA
PDH deficiency (what can cause similar symptoms)
*genetic* no acetyl-CoA, high alanine/oxaloacetate/lactate - chronic lactic acidosis - arsenic poisoning inhibits PDH
galactosemia- which form is worse?
have galatokinase deficiency and GALT (g1PUT) deficiency
GALT is worse because you have galacitol + galactose 1 phosphate build up
galacitol- cataract formation
galactose 1 phosphate- brain/liver/kidney/spleen/intestines/death
key enzymes of TCA cycle, what stimulates/inhibits it
- isocitrate dehydrogenase &
alpha kg dehydrogenase- - stimulated by: ADP, Ca2+
- inhibited by: ATP, GTP, NADH
two cofactors for gluconeogenesis
bicarbonate, biotin
cori cycle vs alanine-glucose cycle
cori-lactate-6 atp
alanine- 10 atp
during an overnight fast, _____ serves as the major source of ATP for gluconeogenesis
oxidation of fatty acids
pyruvate carboxylase genetic deficiency leads to
increased alanine, lactate (acidosis), pyruvate
developmental delays, seizures
GSD type 1
von girkes, glucose 6 phosphatase deficiency in liver, poor tolerance to fasting glucose, growth retardation, fat in the liver, high uric acid and lactate
all gsds
very poor, cash and murder her taurus
von girke, pompe, cori, anderson, mcardle, hers, tauri
pompe trashes the pump- cardiorespiratory failure cori-debranch- short outer anderson-branching- long mcardle-muscle hers-hepatic (liver)
what precursors can you provide for someone with pyruvate carboxylase deficiency?
citrate and aspartate
things you can generate from acetyl CoA and relevant enzymes
1) mevalonate (precursor to cholesterol) - HMG CoA reductase
2) ketone bodies - HMG CoA synthase
3) malonyl CoA (precursor to TAGs) - acetyl CoA carboxylase
two enzymes important for the use of TAGs as gluconeogenic precursors? what does malonyl CoA inhibit?
- HSTL and CPT-1
- MCoA inhibits beta oxidation enzyme- CPT1
enzymes for bile acid synthesis and cholesterol ester synthesis
bile- 7 alpha hydroxylase
cholesterol- ACAT (acetyl coa transferase)
what do statins block?
HMG-CoA reductase
5 types of lipoproteins
1) chylomicrons- largest, dietary TAGs (intestines)
2) VLDL- endogenous TAGs
3) IDL
4) LDL- higher level of cholesterol
5) HDL- good, lower level of cholesterol
functions of apolipoproteins
B48, 100, E, A1, CII
B48- chylomicron secretion
B100- binds LDL receptor (VLDL and LDL)
E - remnant receptor
A1- activates LCAT & binds HDL receptor
C-II activates LPL (lipoprotein lipase)
5 molecules that provide atoms in purine ring (a & g)
aspartate, glycine, glutamine, CO2, tetrahydrofolate derivative
3 molecules that provide atoms of pyrimidine ring (CUT)
aspartate, glutamine, CO2
purine biosynthesis
ribose5phosphate- PRPP- 5p- IMP- AMP/GMP (lots of feedback)
what does 6 mercaptopurine do?
blocks purine biosynthesis by getting converted to nucleotide
urea cycle mnemonic
Ordinarily, Careless Crappers Are Also Frivolous About Urination
ornithine, carbamoyl phosphate, citrulline, aspartate, argino-succinate, fumerate, arginine, urea
what does 5 flurouracil do? methotrexate?
- gets converted to a nucleotide (f-DUMP) and inhibits thymidylate synthase, blocks pyrimidine biosynthesis
- methotrexate inhibits dihydrofolate reductase, inhibits purine & pyrimidine biosynthesis
salvage pathway for purines (A & G) (90%) and enzyme required
hypoxanthine+ PRPP –> IMP + Pi using HGPRTase (lesch-nyhan)
degradation of purines (10%)
a& g –> xanthine –> uric acid (gout)
2 things heme is made from, what is the first precursor
succinyl coa + glycine –> ALA (porphryias)
biliary obstruction, hemolysis, hepatitis/cirrhosis, preemie birth result in increased blood ____ bilirubin
biliary obstruction- conjugated
hemolysis- unconjugated
hepatitis/cirrhosis- both
preemie- unconjugated
which transporter is insulin independent- GLUT2 or 4?
GLUT2- liver/intestines/kidney, bidirectional
how many ATPs generated in total by glycolysis? what is the net ATP yield?
total= 4, net=2
glycogen synthase a and b, which one is active, which is phosphorylated
a- dephosphorylated- active
b- phosphorylated
composition of bile
bile acids- 65%
phospholipids- 20%
proteins- 5%
bilirubin- 0.3%
what makes an amino acid ketogenic?
makes acetyl CoA, acetoacetyl CoA, acetoacetate (leucine & lysine are the main ones)
