week 2, lecture 2 Flashcards
vitamins get metabolized into larger ______?
coenzymes
B2 is aka
ribofalvin
what are the B2 coenzymes
FAD and FMN
FAD –> FADH2 is oxidation or reduction
reduction
what 3 reactions are vitamin B2 (FAD) needed for
- beta oxidation of fatty acids
- ETC: FADH2 –> FAD to give electrons and make ATP
- CAC for succinate –> fumarate via succinate dehydrogenase (reduce FAD to FADH2)
what is vitamin B3 AKA
niacin
what are the coenzynmes of vitamin B3/niacin
NADH and NADP+
what 3 reactions need vitamin B3/ coenzymes NAD+ and NADP+
- glycolysis and CAC (glucose and pyruvate) [NAD+]
- lipid and amino acid metabolism [NAD+ and NADP+]
- ETC: give ATP via NADH oxidized to NAD+
Based on size, which is more likely to diffuse across cell membranes: vitamins or coenzymes?
vitamins (smaller)
Can a Co-enzyme turn back into a Vitamin?
no (its unidirectional)
- i.e phosphorylation alters its structure
-i.e. vitamins only from diet
b vitamin defifiencies
stress, alcohol, IBS< meds, autoimmune, inadequate intake, malabsorption, pregnancy
B1 is AKA
thiamin
B1 pathways
- CAC: pyruvate dehydrogenase complex and the alpha- ketoglutarate dehydrogenase complex
- pentose phosphate shunt: for transketolase enzyme (connect to glycolysis)
- succinyl coa (from CAC) is substrate for heme synthesis –> oxygen –> ATP
what is the coenzyme of vitamin B1/thaimin
TDP/ TPP
(thiamine diphosphate/pyrophosphate)
what type of enzyme takes the TDP from food and turns it into thiamin (vitamin B1)for absorption?
phosphatase
What type of enzyme takes absorbed thiamin and metabolizes it to make the TDP coenzyme?
thiamine pyrophosphokinase (TPK)
what does pyruvate dehydrogenase complex and alpha ketoglutarate complex in the CAC produce
NADH
how does B1 contribute to energy via succinyl coA being a substrate for the synthesis of what?
heme synthesis
heme –> hemoglobin –> oxygen to tissues –> oxygen for glucose and other nutrients into ATP
what are anti thiamine factors that can cause deficiency
- sulphur dioxide (dried fruti and veg, alcohol)
- thiaminases (raw fish- inactivated by heat)
- polyphenols (tea and coffee–> join 2 thiamines together and make too big for absorption)
what pharmaceuticals contribute to B1 deficiency and how
5-fluorouracil (chemo) and diuretics
inhibit thiamine phosphorylation so it cannot be converted to its active form, TDP
how does B1 affect energy dependent tissues like heart and brain
no thaimine to turn pyruvate to acetyl coa in the CAC so it reduces ATP production
B1 deficiency and nerve conduction issues? which neurotransmitter?
myelin sheath integrity not maintained
cant make acetyl coa which is a precursor for synthesis of acetylcholine (needed for brain function and muscles)
which b vitamin deficiency leads to beriberi
b1/ thaimine
which b vitamin deficiency leads to wenicke-korsakoff syndrome
b1/ thaimine
wenicke-korsakoff syndrome effects which system
CNS- memory and confsuion
seen in alcholism
wet and dry beriberi - which system effected?
wet beriberi- cardiovascular system
dry beri beri- CNS and motor
what enzyme is tested for B1/thiamine levels
transketolase enzyme activity
–> Add TDP and measure activity
–> if B1 deficient then addition of TDP shows increase in activity
main sources of riboflavin/ vitamin B2
Meats (especially liver and organ meats), milk products, brewer’s yeast, legumes, eggs, almonds, leafy greens
which riboflavin/ B2 coenzymes are required for metabolism and absorption?
metabolism: FAD synthetase
absorption: FMN phosphatase and FAD pyrophosphates
which coenzyme of riboflavin/ vitamin B2 can cause bright yellow urine
FMN
b2 and energy: Which pathways make FADH2 for
energy?
beta oxidation
CAC
What same type of enzyme produces FADH2 (and/or NADH) for energy in catabolic pathways?
dehydrogenase
b2 and energy: In addition to being part of the CAC, succinyl CoA can also feed into heme synthesis?
oxygen transport in blood for aerobic respiration and dingy metabolism
how does FADH2 provide energy
CAC and beta oxidation –> donates electrons in ETC in mitochondria –> ATP
FMN/FMNH2 role in energy production (vitamin B2)
part of dehydrogenase complex in ETC –> inner mitochondria membrane gradient which drives ATP synthesis
which vitamins help regenerate glutathione antioxidant
b2 and b3
b2: how do FMN and FADH2 relate to ETC
1) FADH2 supplies electrons to the ETC, leading to ultimate production of ATP
2) FMN acts as an electron carrier in the ETC
which neurotransmitters does FAD (from vitamin B2) help metabolize (so we dont get too much)
dopamine, epinephrine, norepinephrine
–> monoamine oxidase uses FAD to degrade the amines
b2 prevent migraines and cataracts
Migraines
* Migraines may be due to decreased mitochondria energy production in the brain
▪ Cataracts
* Cataracts may be caused by UV damaged
testing for B2 deficiency via which enzyme
glutathione reductase
If you had a B2 deficiency, would glutathione reductase activity go up or down if additional FAD were added to the test tube?
up
other names for vitamin B3/ niacin
nicotinic acid or nicotinamide
is nicotinic acid or nicotinamide more found in supplements?
nicotinamide
–> fewer side effects (nicotinic acid can cause flashing)
–>nicotinamide is more direct in synthesis of NAD+
what amino acid can make NAD+ (from vit B3)
tryptophan
Unique to B3: RDA for niacin includes 1/60mg tryptophan, as can also make NAD+ from tryptophan
which vitamin and form can cause flushing
vitamin b3- nicotinic acid
which vitamin does corn contain? and how does this reduce bioavailability?
Corn contains niacin bound to carbohydrates (niacytin) and small peptides (niacinogen)
–>makes it too big for absorption so reduces bioavailability
b3 and energy: Which catabolic pathways produce NADH for energy?
glycolysis, beta oxidation, CAC, anaerobic respiration
which enzyme in glycolysis makes NADH (b3)
glyceraldehyde phosphate dehydrogenase
from glycolysis where can NADH go to make energy in anaerobic and aerobic conditions
aerobic- ETC
anaerobic- cori cycle
which enzyme in the cori cycle (anaerobic) makes B3/NADH
lactate dehydrogenase
Muscle: Produces NAD+ to keep glycolysis running
* Liver: Uses NADH to make glucose for muscles for glycolysis
–>glycolysis produces ATP for energy
all CAC dehydrogenases make NADH (B3) except for which one? hint: this one makes FADH2
succinate dehydrogenase
how does B3/ NADH help to make heme
succinyl coa (made by alpha ketoglutarate dehydrogenase)
how does beta oxidation make NADH/B3
via dehydrogenase
how does NAD+ help metabolize alcohol
via dehydrogenases
nicotinic acid physiological effects
- vasodilatory prostaglandin release (niacin flush)
- enhanced fibrinolysis (clot dissolution, helps blood flow)
- improves lipids: decerase VLDL/LDL and increases HDL
- increased histamine release
- potential for hyperglycemia
what enzyme helps produce prostaglandins (vasodilatory effect of nicotinic acid
cylcooxygenase
therefore COX inhibitor like aspirin/NSAIDs reduce prostaglandins and can reduce the niacin flush
how does nicotinic acid enhance fibrinolysis?
increase plasmin and decrease fibrinogen –> dissolve clots
how does nicotinic acid improve lipid profiles
decrease circulating VLDL/LDL and increase HDL
decrease VLDL/LDL by blocking lipolysis in adipose tissue
increase HDL by downregulation of HDL receptors that internalize and catabolize HDL
effect of nicotinic acid on lipolysis
can bock it
what is Raynaud’s phenomenon?
Condition characterized by spasm of digital arteries, especially in response to cold or stress, causing numbness and tingling in fingers/toes
how can nicotinic acid help raynauds phenomenon?
vasodilator (via cyclooxygenases helping with vasodilatory prostaglandins)
how can nicotinic acid help with atherosclerosis
improve blood flow by enhancing fibrinolysis and decreasing clot formation
increases plasmin and decrsases fibrinogen
how does nicotinic acid increase histamine release
can make peptic ulcer disease worse
Histamine binds to H2 receptors in the stomach lining, promoting gastric acid secretion. In patients with peptic ulcer disease, excessive gastric acid can worsen the condition by irritating the ulcerated mucosa and increasing ulcer pain or bleeding.
how can nicotinic acid cause hyperglycemia
partially due to decreased glucokinase phosphorylation of glucose –> increasing blood sugar
if glucokinase decreased then in liver glucose is trapped and cant be converted to metabolic intermediates or glycogen (storage)
higher free glucose in blood
less glucose uptake and storage in liver
nicotinamide use in diabetes??
can protect insulin-secreting pancreatic beta cells from damage
* Does not necessarily protect against development of diabetes
symptoms of niacin/B3 deficiency
Pellagra: dementia, dermatitis, diarrhea, death
causes of niacin deficiency
▪ Corn-based diet
* B3 in niacytin or niacinogen form
* Low in tryptophan
* Why is pellagra is not common in Mexico and Central America, which have largely corn-based diets? bc soak it in lime to release it
▪ Carcinoid syndrome
* Condition of increased secretion of serotonin (and other catecholamines)
vitamin B5 is aka
pantothenic acid
structure of coA/ vitamin B5
has S to carry acyl group
b5/ CoA and the energy pathways (match the coA to the path)
CAC (2)
beta oxidation (2)
ketolysis (1)
heme synthesis (1)
▪ CAC: Acetyl CoA, succinyl CoA (substrates)
▪ Beta oxidation: Fatty acyl CoA (substrate), acetyl CoA (product)
▪ Ketolysis: Acetyl CoA (product)
▪ Heme synthesis: Succinyl CoA (substrate)
b5/ coa and synthesis
fatty acids
phospholipids and triglucerides
cholesterol and ketones
Fatty acids:
* CoA: makes acetyl CoA and malonyl CoA
substrates
* Also: Part of fatty acid synthetase complex
▪ Phospholipids and triglycerides
* Fatty acyl CoA substrates
▪ Cholesterol and ketones
* Acetyl CoA = substrate to make HMG-CoA
b5 deficiency
burning food syndrome
fatigue and listlessness
