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160 Cards in this Set
- Front
- Back
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which reactions occur in mitochondria?
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beta oxidation, TCA, ox phos, heme synthesis, urea cycle, gluconeogenesis
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which reactions occur in cytoplasm
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glycolysis, FA synthesis, PPP shunt, protein synthesis, steroid synthesis
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rate determining enzyme for glycolysis?
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PFK-1
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rate determining enzyme for gluconeogenesis?
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F1,6 bisphosphatase
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rate determining enzyme for TCA cycle
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isocitrate dehydrogenase
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rate determining enzyme for glycogen synthesis?
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glycogen synthase
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rate determining enzyme for glycogenolysis
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glycogen phosporylase
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rate determining enzyme for PPP shunt
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glucose6phosphate dehydrogenase (G6PD)
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rate determining enzyme for de novo pyrimidine synthesis; regulation
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carbamoyl phosphate synthetase II (CPS2); activated by PRPP, inhibited by UTP
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rate determining enzyme for de novo purine synthesis
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glutamine-PRPP amidotransferase
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rate determining enzyme for urea cycle; regulation
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carbamoyl phosphate synthetase I (CPS1); activated by NAG (N-acetyl-glutamate), which is activated by arginine.
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rate determining enzyme for FA synthesis
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acetyl-CoA carboxylase (ACC)
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rate determining enzyme for FA oxidation
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carnithine acyltransferase I
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rate determining enzyme for ketogenesis
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HMG-CoA synthase
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rate determining enzyme for cholesterol synthesis
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HMG-CoA reductase
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covalent regulation of glycogen synthesis
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insulin activates phosphodiesterase activates glycogen synthase
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covalent regulation of glycogen break down
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glucagon/ epinephrine, via PKA, phosphorylates pohsphorylase kinase, which phosphorylates to activate glycogen phosphorylase
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allosteric regulation to encourage glycogen synthesis
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G6P activates glycogen synthase ; in liver, glucose inhibits glycogen phosphorylase; ATP inhibits glycogen phosphorylase.
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allosteric regulation of glycogen break down
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in muscle, AMP activates glycogen phosphorylase; calcium binds to calmodulin and activates phosphorylase kinase w/o PKA phosphorylation; in liver, calcium activates PKC, which phosphorylates to inactivates glycogen synthase
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another name for vitamin C. Why is it needed for collagen synthesis?
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ascorbic acid; hydroxylates proline & lysine; needed for hydrogen bond;
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what is produced from PPP? Regulation of PPP.
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NADPH produced; thus NADP+ needed. NADPH inhibits; insulin upregulates G6PD; irreversible.
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Important role of NADPH from PPP for RBCs
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used by glutathione reductase; anti-oxidant & DNA synthesis
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Explain G6P dehydrogenase deficiency
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No PPP; PPP only source of NADPH in RBC -> hemolytic anemia
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what does oxidative portion of PPP produces? What can it become?
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ribulose 5-phosphate; when NADPH high, convert to ribose 5-phospohate for nucleotide ; when NADPH low, fructose 6P or G3P for glycolysis.
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when PPP product converts to glycolysis product, what's produced; what enzyme and cofactor?
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ribulose 5-phosphate to F6P and G3P. Transketolase and transaldolase; TPP needed. (thiamine derivative)
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citrate's role in allosteric regulation
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inhibits citrate synthase; inhibits PFK1, activates acetyl-CoA carboxylase; citrate synthase inhibited by ATP
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regulation of isocitrate dehydrogenase
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its work = irreversible; activated by ADP & ca2+; inhibited by NADH, ATP; requires NAD+
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regulation of alpha-ketoglutarate dehydrogenase
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requires TPP, lipoid acid, FAD, NAD+, CoA; inhibited by NADH, ATP, succinyl CoA; activated by Ca2+
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regulation of PDH. Distinguish allosteric & covalent regulation. What other cofactors required?
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covalent: via PDH kinase, inhibted by ATP, acetyl CoA, NADH, activated by pyruvate; covalent: via PDH phosphatase, activated by Ca2+, Mg2+, ADP, NAD+; allosteric: acetyl coA & NADH inhibitors; req TPP, lipoic acid, coA, FAD, NAD+
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what are irreversible enzymes for glycolysis?
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GK/ HK; PFK-1; PK
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gluconeogenesis, how to go from pyruvate to PEP? Regulation?
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pyruvate carboxylase for pyruvate -> OAA; biotin, ATP, CO2 needed, activated by acetyl CoA; malate dehydrogenase for OAA -> malate, NADH needed; shuttle, back to OAA, NADH produced; PEPCK for OAA -> PEP, GTP required
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gluconeogenesis, how to go from F1,6BP to F6P? Regulation?
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F1,6 Biphosphatase; inhibited by AMP and F-2, 6-BP; activated by ATP; glucagon -> PKA -> phosphorylate PFK2/FBP2 (bifunctional); no glucagon -> not phosphorylated PKF2/FBP2;
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gluconeogenesis, how to go from G6P to glucose? Regulation?
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*** G6Phosphatase; compartmentalizaiton in ER.
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defect in G-6-Phosphatase. Impact.
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glycogenolysis and gluconeogenesis inhibited. -> severe hypoglycemia.
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glucagon's stimulation of gluconeogenesis
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allosteric: increase F-2,6phosphatase -> less F2,6BP; covalent: phosphorylate to inactivate PK; enzyme: increases txn of PEPCK gene
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AMP's role in gluconeogenesis
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drives glycolysis: inhibits fructose 1,6-biphosphatase, activates PFK-1
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futile cycle control for gluconeogenesis, how is PK portion controlled?
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**
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futile cycle control for gluconeogenesis, how is PFK-1 portion controlled?
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** F-2,6-BP prevents futile cycle;
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futile cycle control for gluconeogenesis, how is G6Pase portion controlled?
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**
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How is PFK-1 regulated?
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activated by AMP, F-2,6-BP; inhibited by citrate, ATP, low pH; Mg2+ req.
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How is PK regulated?
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PK inhibited by alanine, glucagon, ATP; activated by F-1,6-BP; activated by insulin; Mg 2+ req.
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How is G6Pase regulated?
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** G6Pase is compartmentalized in ER
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two NADH shuttle for glycolysis to ETC, what organs, how many ATPs?
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basically reduce first in cytoplasm, then oxidize in mitochondria; Called "G3P shuttle"; DHAP <-> G3P; NADH -> FADH2; 1.5 ATP/FADH2; brain, muscle;; called "malate-aspartate shuttle" malate <-> OAA; NADH; 2.5 ATP/ NADH2; heart, liver
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how is HK and GK regulated?
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HK inhibited by G6P. GK inhibited by F6P, stimulated by glucose; Mg2+ required.
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How is PFK-2 regulated?
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PFK-2/FBP-2 is bifunctional enzyme; insulin -> activate PFK-2 via dephosphorylation; glucagon/epinephrine activates F-2,6-biphosphotase
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what happens when PK deficient?
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hemolytic anemia
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What does CPS2 stand for, what pathway, and regulation?
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**carbamoyl phosphate synthetase II; de novo pyrimidine synthesis; activated by ATP, PRPP; inhibited by
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In de novo purine synthesis, how is balance of nucleotide bases shown?
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AMP synthesis requires GTP; GMP synthesis requires ATP; AMP, GMP inhibit their own synthesis from IMP; first step inhibited by GMP, IMP, AMP collectively, so if one of them in access, no go
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what are the enzymes of purine salvage? Their regulation?
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HGPRT and APRT; HGPRT inhibited by IMP, GMP; APRT inhibited by AMP;
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With ALT, what are substrate and product?
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alanine, pyruvate
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With AST, what are substrate and product?
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OAA, aspartate
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from purine nucleotide cycle, ammonia and TCA intermediate can be generated. What stage and how?
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prolonged fasting; ribose-5P + aspartate -> fumarate + ammonia
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How are vitamin B1 and B12 used together in function?
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N5-methyl THF -> THF only done with B12. Then homocysteine -> methionine.
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fed state, what activates glycogen synthesis
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G6P activates glycogen synthase
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fed state, what activates PPP
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elavated G6P increases PPP activity; FA synthesis -> req. NADPH
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fed state, what activates glycolysis
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insulin -> glycolysis; GK (liver) has high Km, receives lots of glucose, let them in (GLUT2);
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fed state, what activates TCA
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pyruvate activates PDH -> lots of acetyl CoA; AA -> lots of TCA intermediates
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fed state, what activates FA syn
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high acetyl CoA, NADPH -> activated ACC -> FA synthesis
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fed state, why no gluconeogenesis
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*low acetyl CoA inactivates pyruvate carboxylase
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what happens in fed state in liver
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protein synthesis, lipid synthesis, AA degredation for E production, increased glycolysis & TCA, increased PPP, increased glycogen synthesis
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what happens in fed state in muscle?
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glucose absorbed -> glycogen & TCA; AA absorbed -> protein
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what happens in fed state in adipocyte?
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glucose -> TCA, acetyl coA -> TAG; chylomicrons (from gut) -> TAG; VLDL (liver) -> TAG
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what metabolic hormone receptors for muscle?
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insulin and epinephrine; no glucagon; muscle doesn't synthesize glucose
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during fasting, proteins -> AA. Which two prominent, and where does conversion happen? Purpose of the products?
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alanine -> glucose in liver; glutamine -> ammonia & glucose in kidney; ammonia combines w/ ketonic hydrogen to make ammonium (buffer for acidity)
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time line of glucose homeostasis during fasting
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first ~4 hrs: exogenous glucose, all tissues use glucose; 4~16 hrs: from glycogen, then hepatic gluconeogenesis; glucose used by all, but muscle & adipocytes use less; 16~day 2: more hepatic gluconeogenesis than glycogen, liver doesn't use glucose; adipocytes & muscle use even less glucose; d 2~24: hepatic and renal gluconeogensis, glucose & ketone bodies used by brain, rbcs, renal medulla, small amt by muscle; d24 and on: hepatic & renal gluconeogen, brain, rbcs, renal medulla, more ketone bodies than glucose
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from glutamine, how is it introduced to TCA, and in what organ?
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in kidney; glutamine -> deaminated to glutamate -> further deaminated & dehydrogenizd (NADH) to alpha-ketoglutarate
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PKA activity; where does it happen w/ what hormones? Which pathways does it affect?
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glucagon & epinephrine actvates PKA in the liver (no glucagon affect in muscle); PKA increases activity of glycogenolysis & gluconeogenesis; decreases activity of glycolysis & lipogenesis
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fasting state, what happens in liver
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glycogenolysis; gluconeogenesis; beta oxidation from FFA from adipocyte; AA -> pyruvate (gluconeogensis & acetyl coA) & TCA; acetyl coA -> ketone
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fasting state, what happens in adipocyte
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TAG -> FFA + glycerol; FFA -> TCA in the cell, and ship to liver; glycerol ship to liver
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fasting state, what happens in muscle
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FFA from adipocyte -> TCA; ketone bodies from liver -> TCA; protein -> ship AA to liver
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what hormones during fasting?
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cortisol, epinephrine, glucagon, little bit of insulin
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How many energy products per TCA cycle? (from one acetyl coA)
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3x NADH, 1xFADH2, 1xGTP
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what enzyme is embedded in TCA cycle? What does it do?
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succinate dehydrogenase; complex 2 in ETC; oxidizes FADH2
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which enzymes produce what energy products in TCA cylce? Name the substrate & product of the enzyme
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isocitrate dehydrogenase creates NADH (isocitrate -> oxalosuccinate); alpha-ketoglutarate dehydrogenase creates NADH (alpha-ketoglutarate -> succinyl coA); succinyl CoA synthase creates GTP (succinyl CoA -> succinate); succinate dehydrogenase creates FADH2 (succinate -> fumarate); malate dehydrogenase creates NADH (L-malate -> oxaloacetate)
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talk about anaplerosis, open & closed cycle; in which tissues?
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creation of TCA cycle itnermediates; high in liver & muscle where cycle is open; low in most (closed)
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examples of anaplerosis; enzyme, what organ, regulation
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pyruvate carboxylase for pyruvate -> OAA; most tissues; biotin, ATP, CO2 needed, activated by acetyl CoA;; glutamate dehydrogenase: glutamate -> alpha-ketoglutarate in liver; ribose-5P + aspartate -> fumarate + ammonia, part of pure purine synthesis;; aspartate -> OAA via AST;
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which two AA's are ketogenic?
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leucine & lysine
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what happens when PDH deficient? Treatment?
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excess pyruvate (to restore NAD+) -> lactic acid; congenital lactic acidosis; neurological defects; tx: high fat foods of ketogenic nutrients to enter TCA w/o using PDH, oral citrate supplement;
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what other cuase of PDH deficiency besides congenital?
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TPP deficiency in alcoholics
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There are two types of GLUT we covered. Which GLUT are there and in which organs?
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GLUT4 - major transporter in skeletal m.; GLUT2 - liver, pancreas
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what's special about RBC?
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converts 1,3BPG to 2,3BPG; fast turnover; very dependent on glycolysis & PPP
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compare & contrast GK & HK
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HK has lower Km and Vmax. Non-cooperative. Inhibited by G6P; GK has higher Km & Vmax (to prevent hyperglycemia). Activated by glucose, inhibited by F6P. Insulin stimulates gene expression of GK
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what can pyruvate become?
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lactate, acetyl coA, OAA, alanine
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gluconeogenesis: sources of carbon in liver
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alanine, glutamine most common; glycerol, lactate
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what pathways does fructose go into?
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non-insulin dependent entry; enter glycolysis as DHAP or G3P. Also can go to TAG synthesis as glycerol
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what pathology of fructose can occur?
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essential fructosuria: fructokinase problem; hereditary fructose intolerance: aldolase problem (accumulate as F1P); both: fructose in blood/ urine; low ATP -> inhibition of gluconeogensis/ glycogenolysis -> hypoglycemia; tx: remove fructose, sucrose, sorbitol from diet
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what pathways does galactose go into?
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non-insulin dependent entry; from UDP-galactose, can become lactose, UDP-glucose.
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what pathology of galactose?
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classic galactosemia: absence of galactose-1-P uridyltransferase -> can't become UDP-galactose; galactokinase deficiency: can't become galactose-1-P; both: too much galactose -> become galactitol: galactose appear in blood/ urine; galacitol in eye (cataract), failure to thrive; tx: no galactose & lactose in diet
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general construction of lipoprotein
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core TAG, cholesterol esters; shell of apoproteins, phospholipids, cholesterol
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essential fatty acids. Pathology for deficiency.
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linoleic & alpha-linolenic acid; scaly dermatitis.
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destination of TAG's constituents during fasting: organs, pathways
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beta-oxidation & TCA from nearly all tissues; ketone bodies in liver
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what organ, part of the cell does fatty acid synthesis occur? What are required to run this?
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in liver, mammary glands, adipocytes; cytosol; acetyl coA, ATP, NADPH req
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transport of acetyl coA to cytosol for fatty acid synthesis. Name enzyme used. What happens to the other product? Its significance?
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acetyl coA + OAA -> citrate +coA ----> citrate + ATP + coA -> acetyl coA + OAA; via ATP citrate lyase; OAA (from cytosol) converts to malate then to pyruvate, pyruvate enters mitochondria; malate -> pyruvate creates NADPH.
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rate limitting enzyme for fatty acid synthesis; substrate/ product; regulation; what diabetes drug interferes with this pathway?
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acetyl coA carboxylase (ACC): acetyl coA -> malonyl coA; rate limiting; activated by citrate; inactivated by palmitoyl coA (end product) & AMP kinase (phosphorylates ACC); glucagon & epinephrine activates PKA which activates AMPK; opposite for insulin; metformin also activates AMPK.; AMP also inactivates ACC allosterically. (low E -> should go TCA -> ETC); biotin & ATP required.
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What is the key enzyme for fatty acid synthesis; one after ACC. Regulation. End product.
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fatty acid synthase (FAS). Requires NADPH, which comes from PPP & malate-> pyruvate conversion. End product: palmitate..
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what are substrates and products of ketone body synthesis? How is it carried in blood? Anything to note about urine test?
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substrates: acetyl coA, ketogenic AA's, fatty acyl coA (beta oxidation); products: acetone (deadend) + 3-hydroxybutyrate; soluble in blood; urine test doesn't detect beta-hydroxybutyrate.
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which organs use ketone body? Why not liver?
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heart, muscle, brain; liver missing enzyme (3-ketoacyl coA transferase)
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ketone synthesis' rate limiting enzyme. Its substrate/ product.
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HMG coA synthase; substrate: acetoaccetyl coA, product: HMG coA.
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how is FFA transported into mitochondria for beta ox? Which proteins are important? Regulation
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long FFA: carnithine transport; short, mediam: no carrier; carnitine palmitoyl-transferase I (CPT1) in outer mitochondrial membrane; carnitine palmitoyl transferase II (CPT2) in inner mitochondrial membrane; basic idea: CPT1 removes coA from fatty acyl, adds carnitine; CPT2 removes carnithine and adds coA to fatty acyl; CPT aka CAT (carnitine acyltransferase); malonyl coA inhibits CPT1 (thus rate limiting)
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explain beta ox once inside mitochondria
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fatty acyl coA -> fatty acyl coA (2 carbons shorter) + acetyl coA; NADH and FADH2 produced. ; last fatty acid (3C long) (propionyl coA) metabolized to succinyl coA (biotin, vitamin b12 req)
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what enzyme for TAG breakdown? Regulation?
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lipase; covalent regulation: activation via adrenaline/ glucagon, inactivation by insulin
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one pathology for beta ox
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medium-chain fatty acyl coA dehydrogenase deficiency; can't oxidize these FFAs. Dx: increased in urine; hypoglycemia (these tissues take in more glucose); tx: avoid fasting, carnitine suplpementation
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role of branching in glycogen; what linkage is considered branching?
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alpha 1->6; branching makes glycogen more soluble; accelerates rate of glycogen synthesis.
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what is limiting enzyme for glycogen synthesis; what linkage created? What is substrate
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glycogen synthase; creates alpha(1->4) linkage; substrate: UDP-glucose
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how are alpha(1-6) and alpha(1-4) bonds lyased in glycogen? Which is rate limiting?
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glycogen phosphorylase (rate limiting) breaks alpha(1->4) linkage; 4:4 transferase removes outer three of four residues for alpha(1-6) branch; 1:6 glucosidase removes the last one on alpha(1-6) branch.
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name one glycogen storage disorder and mechanism. Treatment.
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mcardle's disease: glycogen phosphorylase deficient, too much glycogen, diminished exercise tolerance. Tx: sucrose supplementation, aerobic exercise (non-glucose TCA cycle) w/ creatine & vitamin B6.
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branched AA's
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leucine, isoleucine, valine.
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10 essential AA's; characteristic?
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PVT TIM HALL; phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine; no acidic; all branched, basic AAs included.
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what is coenzyme for aminotransferase?
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pyridoxal phosphate (vitamin b6 derivative)
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what two AA's not transaminated?
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lysine, threonine
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how is redox and transamination related?
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deamination is oxidative, while amination is reductive; NADPH/NADP+ or NADH/NAD+ used
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explain transport of ammonia. From where to where? What happens once arrives in the destination?
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glutamine: non-toxic transport, from anywhere to liver, produces glutamate; forms alanine from muscle, shipped to liver, transaminated back to pyruvate. Ammonia then turns to urea.
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what's special about branched chain AA? Connection to pathology and vitamin?
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different enzymes. Oxidative decarboxylation via branched-chain alpha-ketoacid dehydrogenase (BKAD); require TPP. Subsequent step also requires biotin and vitamin b12. Defect in BKAD -> maple syrup urine disease; accumulation of branched alpha-ketoacid in urine -> sweet odor -> CNS defects
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two one-carbon carriers; their sigficance
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THF & SAM; THF derived from folic acid. Folic acid -> THF requires NADPH; conversion from N5-CH3-THF to THF requires b12; THF then aids in methionine production. THF also produced from bacteria; different DHFR enzyme, so inhibitor of bacteria -> antibiotics, inhibitor of human -> chemotherapy; SAM synthesized from ATP & methionine.
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list some products from AA metabolism
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catecholamines (from tyrosine, which is from phenylalanine); NO from arginine; histamine from histidine
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Name most common error in AA metabolism & its mechanism
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phenylketonuria (PKU); defect in conversion phenylalanine -> tyrosine; build up of phenylalanine, deficiency of tyrosine; urine: musty odor, elevated phenylalanine level, melanin deficiency (tyrosine) -> hypopigmentation.; tx: restrict phenylalanine, replace tyrosine.
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what's an important pathology concerning pyrimidine synthesis? Its significance?
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orotic aciduria; inability to convert orotic acid to UMP; megaloblastic anemia (like b12/ thymidine deficiency), but doesn't improve w/ vitamin supplementation; no hyperammonemia like OTC deficiency; tx: uridine supplement
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connection between PPP & purine biosynthesis
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PPP's product ribulose-5-P -> ribose-5-P (substrate of purine biosyn)
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explain mycophenolic acid's role (purine synthesis)
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reversible inhibitor of IMP dehydrogenase. Deprives T & B cells of key components of nucleic acid; immune suppressants; to prevent graft rejection
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explain methotrexate's role (purine synthesis)
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inhibit reduction of DHF -> THF. Slow down DNA replication; chemotherapy
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explain allopurinol's purpose and mechanism
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treatment option for gout; inhibits xanthine oxidase; xanthine more soluble than uric acid
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explain adenosine deaminase deficiency
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excess ATP/ dATP inhibits ribonucleotide reductase -> prevent DNA synthesis; inability to complete DNA synthesis in B & T cells -> Severe Combined Immunodeficiency Disease
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explain Lesch-Nyhan syndrome
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deficiency of HGPRT; can't salvage hypoxanthine/ guanine; elevated PRPP, decreased IMP, GMP -> elevated purine biosynthesis -> gout; tx: allopurinol
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How is uric acid secretion modulated in kidney? Examples of the one that promotes reabsorption?
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uricosuric: inhibit URAT1 -> secretion; antiuricosuric -> keep uric acid; ex: lactate, nicotinate, pyrazinoate
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general cause of hyperuricemia & treatment
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too much synthesis of uric acid or too few excretion of it; allopurinol to reduce synthesis; uricosurics to underexcretors; anti-inflammatory drugs for gout.
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what are probenecid or sulfinpyrazone. Which mediator does it work w/?
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uricosurics; URAT1.
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explain cori cycle
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lactate released by skeletal muscle & RBCs -> turned to glucose by liver -> glucose goes to muscle & RBCs; net loss of 4 ATPs/ cycle
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EtOH's impact on biochem
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Too much NADH -> decreased gluconeogenesis, TCA cycle inhibited, increase in ketone bodies
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sources of two ammonia from urea cycle, starting nw/ glutamine
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one from oxidative deamination of glutamate by glutamate dehydrogenase & another from transamination of OAA by AST
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what is OTC deficiency? Tx?
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one of urea cycle disorders. One of the enzymes missing. High ortic acid in blood/ urine. Hyperammonemia; restriction of protein intake;
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dietary treatment to newborns of urea cycle disorder
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IV dextrose
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phenylbutyrate & benzoate's role
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in urea cycle disorder: alternative route for nitrogen disposal;
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describe hemoglobin; describe type A & F; describe difference.
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4 polypeptide subunits; each binds heme moiety; cooperative binding; 2 forms: Tense (deoxy)/Relaxed(oxy); HbF: fetal, alpha & gamma, higher O2 affinity; HbA: alpha, beta; HbF has weaker binding of 2,3-BPG (which reduces O2 affinity)
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explain bohr effect
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decrease in pH, increase in temp -> reduces O2 affinity
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role of 2,3-BPG
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reduces O2 affinity; allows body to adjust to environment (anemia, altitude, hypoxia, doping)
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saturation curves of myoglobin & hemoglobin -> advantage of sigmoid curve
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not too adherent, not too loosely adherent for O2 = just right; too adherent -> can't give O2 to tissue; too weak -> gives O2 to any tissue, not the ones that are deoxygenated; this precision is required to accommodate the difference in partial pressure of oxygen from lung & peripheral tissues are different;
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mechanism of CO poisoning
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binds to iron, increases affinity for oxygen; unable to release O2; no O2 -> inhibition of complex 4 for ETC
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what forces run the ETC; products of ETC.
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pH gradient (hydrogen in intermembrane space) & electrical potential (negative in matrix); ATP, CO2, H2O
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what are two mobile e- carriers in ETC?
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CoQ & cytochrome c
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steps and constituents of ETC.
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1 (NADH dehydrogenase), 2(succinate dehydrogenase - FADH2) -> CoQ -> 3 -> cyt c -> 4; ATP synthase/ ATPase (F0, F1)
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Describe ATP synthase of ETC
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F0 (transmembrane); F1: cytosolic; F1 rotates, changing from open, loose, tight (catalytic) conformation; F0 pump H+ down the gradient to fuel ATP synthesis.
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what is 2,4-dinitrophenol
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synthetic uncoupler. Creates proton leak w/o ATP formation; releases heat
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mechanism of brown fat; regulation
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beta oxidation -> TCA -> ETC; uncoupling via UCP-1 -> heat.; regulated by norepinephrine & thyroid hormone.
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describe function of rotenone.
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binds complex I of ETC -> no reduction of CoQ from complex 1. reduced efficiency. Complex 2 still functions.
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explain apoenzyme, holoenzyme, cofactor, coenzyme,
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holoenzyme: enzyme w/ non-protein part as activator; apoenzyme: holoenzyme w/o its activator; cofactor: metal ion serving as activator; coenzyme: small organic factor like vitamin as activator
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explain cosubstrate, prosthetic group, synthetase, synthase
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cosubstrate: coenzyme transiently associated; prosthetic group: coenzyme permanently associated; synthetase: requires ATP; synthase: doesn't require ATP
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describe carboxylase
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adds 1 carbon w/ help of biotin
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factors affecting enzyme rxn velocity
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temp: increase T -> increased rxn, until it is too high -> denature; pH: can change ionization of AA residues, extreme change -> denature
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explain steady state assumption
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[ES] doesn't change; same rate of formation as breakdown.
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explain the affect of competitive, un-competitive, noncompetitive inhibitors
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competitive: increases Km; un-competitive: decreased V max and Km; non-competitive: decreased V max
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what is collagen made of, what structure, constituents
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glycoproteins; triple alpha-helix; 1/3: glycine, 1/3: proline, 1/3: hydroxylated proline & lysine
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regulation of collagen synthesis; possible pathology w/o the cofactor
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vitamin c to hydroxylate proline/ lysine -> no H bond; deficient -> scurvy's;
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describe osteogenesis imperfecta: etiology, sx, dx
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point mutation in COL1A1 or COL1A2 genes (type 1 collagen); affect glycine residue; heterozygous -> mixture of abnormal collagen; sx: blue-greyish sclera (blue choroid shown), weakened teeth due to lack of dentin, hearing impairment, brittle bone; dx: skin bx to check fibroblasts, genomic DNA from WBCs to see mutation
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describe pamidronate for collagen synthesis
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tx for osteogenesis imperfecta; anti-resorptive agent for calcium; inhibit osteoclast activity
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describe difference between point mutation & nonsense mutation for osteogenesis imperfecta
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point mutation -> mixture of bad collagen; stop codon: reduced normal, only normal is translated.
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describe folic acid deficiency
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neural tube defects; THF -> methionine -> purine & pyrimidine synthesis; path -> megaloblastic anemia w/o neurological sx;
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Vitamin b12 deficiency (cobalamin)
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odd chain FFA oxidation & THF formation for methionine synthase; path: abnormal FA accumulation -> neurological sx; megablastic anemia
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thiamine (b1) deficiency
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as TPP, coenzyme in formation/ degradation of alpha-ketols, PPP, PDC, BCAA, alpha-ketoglutarate dehydrogenase complex; path: beriberi, Wernicke-Korsakoff Syndrome; reduced ATP production and accumulation of ketoacids
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vitamin c deficiency
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collagen synthesis, iron absorption, norepinephrine synthesis; pathology: scurvy
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vitamin d defiency
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regulate calcium; rickets (bending bone)
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