Biochem Term 2 Quiz 4: Porphyrins, Vitamins, Muscle Metabolism

Front 1

Committed, rate determining step in heme synth and how regulated

Back 1

ALA synthase: succinyl CoA + glycine --> ALA

Regulated by feed back from heme/hemin

Front 2

Basic structure of porphyrin molecule

Back 2

4 pyrrole rings linked by methenyl bridges with asymetetrical side chains, able to chelate metal ion

Front 3

Rate limiting non committing step of heme synth

Back 3

Hydroxymethylbilane synthesis: 4x PBG --> hydroxymethylbilane (linear tetrapyrrole)

Front 4

Acute intermittent porphyria

Back 4

Insufficiency in liver hydroxymethylbilane: build up of ALA and PBG in the liver AND low heme produced to feedback and slow pathway---> boughts of stomach pain and psychosis.

Dx: PBG in urine

Treat: hemin, avoiding alcohol/other things that require CYP450s,

Front 5

physiological roles of heme

Back 5

- Electron transport

- Oxygen transport

- Drug detoxification (liver has a lot - cytochrome P450 enzymes)

- Removal of H2O2

Front 6

What's chronic inability to make heme well?

Back 6

Porphyria Cutanea Tardea (PCT): insufficiency in uroporphyrinogen decarboxylase (not rate limiting step). Get enough heme made and no ALA/PBG back up, but back up of uroporphyrinogen, which is conjugated to uroporphyrins --> photosynthetic compounds in skin that react to sunlight and make blisters. Pee with also change color

At risk: liver damage from alcohol, hep C etc

Treat: stay out of sun and routine phlebotomy

Front 7

Lead poisoning

Back 7

Lead blocks ALA dehydrase (ALA->PBG) and inhibits ferrochelatase (last step in making heme) --> heme levels down --> decrease in feedback --> sx overdrive --> ALA accumulation

Sx: see anemia (because bone and liver isoforms affected), abx pain, psychosis

Front 8

Iron deficiency anemia

Back 8

Not enough Fe --> no binding/inactivation of iron response protein --> Iron response elements on mRNA are not uncovered--> don't have translation of heme synth genes like ALA synthase --> little heme made --> anemic.

Dx: thin rimmed, pale RBCs

Front 9

Heme degradation critical steps

Back 9

1. Heme oxgenase in spleen macrophages: heme--> biliverdin

2. Biliverdin reductase: biliverdin --> bilirubin (fat soluble, transported to liver on albumin)

3. Bilirubin glucuronyl transferase in liver: bilirubin --> bilirubin diglucuronide (conjugated)

4. Congugated --> urobilinogen

5. Intestine convert to urobiligen --> sterocobalin = brown poop

6. Kidney: urobilinogen --> urobilinin = pee yellow

Front 10

Thiamine B2

Back 10

- Water soluble, co-enzyme for krebs cycle metabolizing enzymes

- Brain, nerves, heart need a lot

Front 11

Thiamine deficiency first world

Back 11

- Weinike's encephalopathy: not enough krebs cycle enzymes working --> impairs glucose metabolism in tissues like brain

-Sx: confusion, nystagmus, bad motor control

- At risk: alcoholics who don't eat well

- Treat: glucose with thymine. No thymine and you'll make it work --> korsacoff's --> death

Front 12

Thiamine deficiency third world

Back 12

Beriberi: dilated cardiomyopathy --> high output failure

Sx: SOB, flushed with no fever, peripheral neuropathy (foot drop)

treat: IV thiamine - can reverse

Front 13

RiboflavinB2

Back 13

Makes FAD

Deficiency: dry mouth, striations around lips

Front 14

Niacin B3

Back 14

- Water soluble, Makes NAD and NAPH

- Can also get them from tryptophan, but not if tryptophan is down cuz of chemo, etc

Front 15

Niacin deficiency

Back 15

Pellegra:

Sx: dark spots in reaction to sun, diarrhea, dementia, death

At risk: carcinoid - tumor takes up all tryptophan, hartnup - diminish tryptophan uptake

Front 16

Pyroxidine B6 / deficiency

Back 16

Water soluble, makes pyroxidine phosphate (PLP) that's cofactor for deaminases, decarboxylation

Deficiency: rare, not fatal but get seizures, isoniazid = TB drug that binds it up

Front 17

Biotin B7

Back 17

Water soluble, cofactor for carboxylase enzymes

Deficiency rare: see in body builders who eat raw eggs --> avidin protein binds up

Sx: depression and dry skin

Front 18

Folate

Back 18

- Water soluble B vitamin, important to one carbon metabolism that's needed for: aa synthesis, purine synthesis and thym-dine synthesis (key to DNA synthesis and cell replication/growth esp in fetus and blood)

-

Front 19

Folate deficiency

Back 19

- most common in the us esp pregers and on methotrexate (chemo drug)

- Sx: megloblastic anemia

- Methotrexate: shuts down all quickly dividing cells, often overshoot and rescue with THF (leukovorin)

- Causes neural tube defects in babies

- moms take supplement, enriched foods

Front 20

Cobalamin B12

Back 20

- Water soluble but can store for years and can't get from plants

- Porphyrin chelated by cobalt

- Absorption requires intrinsic factor from parietal cells

- 2 forms 1) methylcobalin in blood, used for 1C transfer with folate. Deficiency causes megloblastic anemia too- treat with B12 or lots of folate 2) deoxyadenosylcobalamin: used by neurons to break up fat

Front 21

Pernicious anemia

Back 21

- At risk: old ladies with autoimmune disease

- Sx: anemia and peripheral neuropathy

- Autoimmune degradation of parietal cells --> no IF --> no B12 absorbed and insufficient folate in diet --> megloblastic anemia and build up of fat in neurons

- Treat: injected B12

Front 22

Subacute Combined Degeneration of spinal chord

Back 22

- Sx: sensory and motor neuropathy- clumsy and can't feel vibration

- Autoimmune degradation of parietal cells --> no IF --> no B12 uptake BUT enough folate --> no anemia and just fat build up in brain --> irreversible damage

- Treat: B12 injections

Front 23

Vitamin C + deficiency

Back 23

- water soluble, aka ascorbic acid, needed for enzymes that make collagen

- deficiency = scurvy: leg hairs curl, hemorrhages at hair follicles, gums swell and bleed, poor wound healing

Front 24

Vitamin A/ deficiency

Back 24

- fat soluble,

- Ingest as retinol and retinal: essential for repro,

- Retinoic acid: essential for life, differentiation of epithelial cells

- 11-cis-retinal: essential for rhodopsin in eyes

- beta-carotene: in plants converted to retinal, heat stable, cleavage regulated so can't OD on vitA

- Deficiency: night blindness, eye spots, corenal ulcerations, (major cause of blindness in world)

Front 25

Vitamin D

Back 25

- D2: plants, D3: animals (can be made from plant D2 but requires UV light)

- D3 converted to active calcitrol in liver/kidney --> increase Ca uptake by kidney/intestine

Front 26

VitD deficiency

Back 26

- Osteomalacia: demineraization of bones after plates fuse, soft bones, from lack of diet D3 (no fortified milk)/ sunlight (dark skin in northern latitudes)

- Rickets: deminieralization of bones before plates fuse, bowed legs

- Treat: supplement calcitrol

Front 27

Vitamin K/ deficiency

Back 27

- Fat soluble, made by intestinal bacteria, important in modifying clotting factors --> enable clotting

- Coumadin inhibits action of vitamin K --> blood thinner for preventing stroke

- Deficiency: rare, see in a) alcoholics (low nutrients and flora) b) lots of antibiotics/ baby on feeding tube - no gut flora

- Sx: extended PT, babies: bleeding from venous puncture sites, hemorrhage (death)

Front 28

What's main source of fuel for the heart?

Back 28

1) Fat metabolism

2) Lactate metabolism: lactate dehydrogenase turns to pyruvate --> krebs

3) glucose (low glycogen/glycolysis)

favors oxidative pathways thus needs to have good perfusion always or wont get nutrients

Front 29

How does AMPK increase ATP-generating processes?

Back 29

1) phorphorylate ACC --> down reg FA synth --> less malonyl CoA --> upreg FA oxidation

2) increase glut4 in muscle --> increase glucose uptake (insulin independent)

Front 30

How do muscles upregulate glycolysis really fast when need quick source of ATP for exertion?

Back 30

- After blow through adenylate kinase and creatinine (10 sec)

- Glycogen phosphorylase activated by AMP

- Ca2+ activates phosphorylase kinase --> activates glycogen phosphoylase

- Activate PFK: phosphate, AMP, NH3

- No PFK inhibition by ATP, creatinine-phosphate

Front 31

how insulin affects FA balance in liver/adipocytes

Back 31

Liver:

a) Activates ACC : more FA synth

b) Breaks down cAMP, which is glucagon/epi second messenger in inhibiting ACC

c) High ACC --> low CAT1 --> low Fa oxidation

Adipocyte:

a) upreg LPL for taking in FAs

b) inhibit HSL - no FA breakdown

d) doesn't make FFAs, but has ACC/CAT1 sx and down reg FA oxidation

e) increase glucose uptake to make glycerol for TG synth

Front 32

What neurons important in appetite

Back 32

- Arcuate hypothalamus: NPY = orexogenic, POMC = anorexogenic.

- NPY sense high CAT1 levels --> hungry

- Leptin activates POMC/ inactivates NPY --> not hungs

- Ghrelin activates NPY

Front 33

Thiazolidinedoines (TZDs)

Back 33

- Treat DMII by increasing insulin sensitivity

- PPAR gamma analog: increase adipose fat storage capacity --> decrease stress on adipose --> less insulin resistance

- Side effect = weight gain

Front 34

Selective insulin resistance

Back 34

- Insulin does not cut down gluconeogenesis --> hyperglycemia

- Insulin does activate lipogenesis --> fatty liver

Front 35

Orlistat

Back 35

- only approved obesity drug: looks like a TG and binds up lipase in gut so that can't absorb

- side effects: waxy stool, feel shitty, fat soluble vitamin deficiency

Front 36

Sufuroneas

Back 36

- DMII drug for insulin sensitivity- inactivates K channel and increases Ca influx that releases insulin

- side effects: weight gain

- cheap and oral but not that effective