Flashcards in Biochemistry Deck (255)
ATP investing steps of glycolysis?
ATP producing steps of glycolysis?
Phosphoglycerate kinase (1,3-BPG -> 3-PG)
Pyruvate kinase (Phosphoenolpyruvate -> pyruvate). Inhibited by ATP, alanine. Pushed by Fructose-1,6-BP.
Glucose, glu-6-p, fructose-6-p,fructose-1,6-bp,G3P+DHAP,->->Phosphoenolpyruvate, pyruvate.
Glycolysis and gluconeogenesis are both regulated via this bifunctional enzyme how?
Fructose bisphosphatase-2/pFK-2. fructose-2,5-BP fructose-6-P
Fasting - inc. glucagon, inc cAMP, inc PKA, inc FBPase, inc gluconeogenesis
Fed - inc insulin, dec cAMP, dec PKA, inc PFK-2, inc glyolysis
Glycolysis is coupled to TCA how?
Pyruvate dehydrogenase complex: pyruvate + NAD+ + CoA -> acetyl-CoA + CO2 + NADH
5 cofactors: Pyrophosphate (B1), FAD (B2), NAD (B3), CoA (B5), Lipoic acid (inhibited by arsenic)
Inhibited by ATP, Acetyl-CoA, NADH
Pyruvate dehydrogenase complex deficiency?
Buildup of pyruvate shunted to lactate (LDH) and alanine (ALT). Tx = Lysine and leucine (ketogenic) to minimize lactic acidosis (shunting metabolism to fat burning)
Four ways pyruvate is metabolized
(1) Alanine aminotransferase (B6)
(2) Pyruvate carboxylase (biotin) - makes oxaloacetate for TCA cycle or gluconeogenesis
(3) Pyruvate dehydrogenase (B1-3, 4, liopic acid)
(4) Lactic acid dehydrogenase (B3) - makes lactate. RBCs, leukocytes, kidney medulla, lens, testes, and cornea
Krebs cycle overview?
Citrate Is Krebs' Starting Substrate For Making Oxaloacetate
Citrate, Isocitrate, alpha-ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate
Produces 3 NADH, 1 FADH2, 2CO2, 1 GTP/CoA = 10 ATP/acetyl-CoA
Rate-limiting step of TCA cycle?
Isocitrate dehydrogenase (Isocitrate -> a-KG)
Inhibited by ATP and NADH. Pushed by ADP.
Pyruvate + CO2 -> Oxaloacetate; Used for TCA, gluconeogenesis via malate.
Deficiency - limits TCA cycle. Lactic acidosis. Mental retardation < age 5.
What is the gradient in oxidative phosphorylation?
H+ produced in inter membrane space. NADH, FADH2, H20, and ATP are in the matrix.
1 NADH -> 2.5 ATP; 1 FADH2 -> 1.5 ATP
Oxidative phosphorylation poisons?
E- transport inhibitors: rotenone (I), antimycin A (III), cyanide & CO (IV)
ATP synthase inhibitors: oligomycin
Uncoupling agent: ATP synthesis stops but electron transport continues. (2,4-dinitrophenol, ASA, thermogenin in brown fat)
Pathway Produces Fresh Glucose. Starts after fasting 12-18h.
1. Pyruvate carboxylase (Pyruvate -> oxaloacetate; biotin, ATP); mitochondria
2. Phosphoenolpyruvate carboxykinase (Oxaloacetate -> phosphoenolpyruvate)
3. Fructose-1,6-bisphosphatase (Fructose-1,6-BP--> Fructose-6P); Inhibited by F 2,6P. Pushed by citrate.
4. Glucose-6-phosphatase (Glycose-6P->Glucose). ER
Primarily in liver, also kidney. Odd-chain FA's can enter TCA via succinyl-CoA to become glucose but even-chains destined for acetyl-CoA.
Key enzymes in HMP shunt?
Glucose-6-P dehydrogenase (glucose-6P -> ribulose 5-P)
Phosphopentose isomerase, transketolases (Ribulose 5-P -> ribose-5-P, G3P, F6P). Req. b1.
What is the respiratory/oxidative burst?
Phagocytic NADPH oxidase complex that rapidly releases ROS to kill bacteria. Most important enzyme = NADPH oxidase (whose deficiency = chronic granulomatous disease). O2->O2-->H2O2+Cl- -(Myeloperoxidase)-> bleach
Other enzymes degrade H2O2 and require SELENIUM to do so.
What type of organisms are patients with chronic granulomatous disease susceptible to?
Catalase + specieies (e.g. Staphs, Aspergillus). B/c these organisms catalase their own H2O2 leaving phagocytes w/o any substrate for oxidative burst.
Leber's hereditary optic neuropathy
Mitochondrial (maternal transmission) mutation of complex I often leads to optic nerve death 2/2 ischemia by early adulthood.
Arsenic poisoning symptoms
Cholera-like symptoms. tx - chelation; Arsenic inhibits lipoid acid requiring enzymes like PDH complex, aKG DH, transketolase
Conversion of NE to Epi occurs where and how?
Adrenal medulla. Phenylethanolamine-N-methyltransferase (PNMT). Controled by cortisol (increases transcription).
Synthesis of serotonin?
Tryptophan req. BH4 -(tryptophan hydroxylase)-> 5-hydroxytryptamine -> serotonin
Tropoelastin precursors (Gly, ala, val w/ non-hydroxylated pro and lys). After secretion, binds with fibrillin. Lysine residues bound covalently as desmosine cross-link = elastic properties. NO triple helix.
What protein regulates G1->S transition?
Rb. Active=hypophosphorylated, which binds to E2F. Hyperphosphorylated Rb (via CDK4) -> E2F transcription factor release.
Spingomyelinase. Spinhingomyelin. AR. Ashkenazi, 1st yr with hepatosplenomegaly, hypotonia, ID. "FOAMY histiocytes" in liver and spleen and neuro. CHERRY-red macular spot (Tay-sachs like). Death by 3.
What monosaccharide is most rapidly metabolized?
Fructose. B/c F-1-P bypasses PFK-1 by being converted by Aldolase B (Hereditary fructose intolerance) into DHAP and Glyderaldehyde.
P50 of Hgb v. P50 of Mgb?
25 mmHg v. 1 mmHg; 1 Quarter for the hemoglobetrotters.
Most commonly from lactose (glucose-galactose), with lactase in GI breaking down. Galactose -(galactokinase)-> galactose-1P -(Uridyltransferase)-> Glucose-1-P
AR. Galactose in blood and urine. Galactitol accumulation (via aldose reductase) -> infantile cataracts (failure to track or develop social smile).
AR. Absence of galactose-1-phosphate uridyltransferase. Galactitol accumulation (via aldose reductase) -> cataracts. FTT, jaundice, hepatomegaly, ID. Tx = exclude galactose and lactose. e. coli sepsis.
Keeping glucose in a cell for later use into fructose via sorbitol dehydrogenase. (Glucose -aldose reductase-> sorbitol). Liver, ovaries, seminal vesicles have both. Schwann cells, retina, kidneys, lens primarily has aldose reductase, making these cells susceptible to osmotic dmg with hyperglycemia OR with high galactose lvls.