Biochemistry - Cellular respiration Flashcards
What are the 2 functional groups of monosaccharides?
Aldose (H - C = O) & Ketose (C = O)
Who reacts faster – aldose or ketose?
Aldose
Give examples of trioses: aldose and ketose.
Ald- glyceraldehyde; Ket- dihydroxyacetone
Give example of tetrose aldose.
Erythrose
Give exampels of pentose aldoses and ketoses.
Ald- Ribose, xylose; Ket- Ribulose, xyluose
Give examples of hexose aldoses and ketoses.
Ald- Glucose, galactose, mannose; Ket- fructose
Give example of heptose ketose
Sedoheptulose
Sugar in the urine is a result of:
DM, fructosuria, glaactosuria
Give an example of a polyol and state its importance.
Sugar alcohol, sorbitol; can cause damage in DM; incorporates in nerves, lens of eye, retina
Define an epimer
Same chemical formula, -OH in different position
Give 2 sets of epimers and state the epimerization
Glucose/Galactose (C4 epimers); Glucose/Mannose (C2 epimers)
Give 3 examples of brush border disaccharides. State whether they are reducing or non-reducing sugars.
Lactose - Glu-Gal (beta-1-4 glycosidic)
Sucrose - Glu-Fru (C1-C2) *NON-reducing
Maltose - Glu-Glu (alpha-1-4 glycosidic)
T/F Fructose is a ketohexose
True
What is HFCS?
High fructose corn syrup (> 50% fructose in sugar – ingested in the body as a mixture)
What is glycogen? How are units linked?
Storage glucose / homopolysaccharide
Linear: alpha-1-4 glycosidic
Branched: alpha-1-6 glycosidic
What is starch? How are units linked?
Homopolysaccharide; found in plants
Amylose - linear alpha-1-4 glycosidic
Amylopectin- linear alpha-1-4 & branched alpha-1-6 glycosidic
What is dietary fiber?
Undigestable cellulose (beta-1-4 linkages – lactase CANNOT break this down); maintains normal peristalsis
Differentiate between hexokinase and glucokinase.
HK: Low Km, high affinity for glucose; most cells express HK
GK: only in liver and beta-pancreas; high Km, low affinity for glucose (only active at high [glucose])
What inhibits HK?
A high [G-6-P]
Who has a higher Km: HK or GK?
GK – has a low affinity for glucose and is only active in the liver and beta-pancreas at high [glucose]
Increased ATP will increase/decrease the activity of PFK?
Decrease
Differentiate between insulin & glucagon’s impact on PFK.
Insulin - high glucose, de-phosphorylate PFK-2 to increase the formation of F-2,6-bisphosphate, which activates PFK-1
Glucagon - phospohrylates PFK-1, which stimulates fructose 2,6 bi-phosphatase (decreased levels of fructose-2,6,-biphsosphate); activates fructose 1,6,-biphosphatase
Where does carbohydrate digestion begin?
Mouth - salivary alpha-amylase
What is the fate of salivary alpha-amylase in the stomach?
Inactivated by acidic lumen of stomach
Where does lipid digestion begin?
Mouth - lingual lipase
What is the fate of lingual lipase in the stomach?
Active, along with gastric lipase
* Degradation of TAG’s (medium-chain) and sends directly to the portal vein
Where does glycolysis take place?
The cytosol
What is the overall goal of glycolysis?
Oxidize glucose to 2 molecules of pyruvate
What are the 3 irreversible steps of glycolysis?
- Glucose –> G-6-P (GK/HK)
- F-6-P –> F, 1,6 bis-phosphate (PFK-1)
- Phosphoenolpuyruvate –> Pyruvate (PK)
How many substrate-level phosphorylations are present in glyolysis?
- 1,3-BPG –> 3-phosphoglycerate (phosphoglycerate kinase)
2. Phosphoenolpuyruvate –> Pyruvate (PK)
What does arsenate inhibit along the glyocolytic pathway?
Glyeraldehyde-3-phosphate-dehydrogenase
What does fluoride inhibit along the glycolytic pathway?
Enolase
Where does pyruvate dehydrogenase take place?
Mitochondrial matrix
Briefly describe the 3 stages of metabolism.
- Large molecules –> building block molecules (digestion)
- Common degradation product (pyruvate/acetyl-coA)
- Simple, small products of catabolism
What are the 4 fates of pyruvate?
- Lactate
- Acetyl coA
- Oxaloacetate
- Alanine
What is the link between glycolysis and the TCA cycle?
Pyruvate dehydrogenase complex
What type of reaction is pyruvate –> acetyl-CoA?
Decarboxylation
What are the reactants and products of PDC?
- 2 Pyruvate
2. 2 acetyl-CoA & 2 NADH
What are the 3 enzymes required for PDC?
- PDH
- Dihydrolipoyl dehydrogenase
- Dihydrolipol transacetylase
What are the 2 regulatory proteins for PDC?
- Protein kinase
2. Protein phosphatase
What are the 5 co-enzymes required in PDC?
- CoA - vitamin B5
- FAD - riboflavin / vitamin B2
- NAD+ - niacin / vitamin B3
- TPP
- Lipoic acid (non-vitamin derivative)
Do the following stimulate or inhibit PDH?
- Dephosphorylation
- Insulin in adipocytes and liver
- Catecholamines in cardiac muscle
- Ca in skeletal muscle
Stimulate
Do the following stimulate or inhibit PDH?
- Phosphorylation
- Acetyl CoA
- ATP
- NADH
Inhibit
Acetyl coA can be derived from two other processes aside from PDH. What are they?
- Lipolysis
2. Proteolysis
What are synonyms for TCA cycle?
- Tricarboxylic acid cycle
- Krebs cycle
- Citric acid cycle
How many ATP are generated for each molecule of pyruvate sent to PDH?
3 ATP, or 1 NADH (3 ATP * 2 b/c we send 2 pyruvates)
Which are the 4 regulated enzymes in TCA?
- Citrate synthase
- Isocitrate dehydrogenase
- alpha-KG dehydrogenase
- Succinate dehydrogenase
What are the products of one cycle of the TCA?
- 3 NADH
- 1 GTP
- 1 FADH2
- This is 12 ATP per each acetyl coA
How many ATP produced per NADH?
3
How many GTP produced per ATP?
1
How many FADH2 produced per ATP?
2
In general, what stimulates TCA cycle and what inhibits it?
Stimulate – low energy
Inhibit – high energy
A high ratio of ATP:ADP will stimulate/inhibit the TCA cycle?
Inhibit
What are the ATP totals for glycolysis?
8 ATP (2 pyruvates)
What are the ATP totals for PDH?
6 ATP (2 pyruvates)
What are the ATP totals for TCA cycle?
24 ATP (2 acetyl-co-A’s)
Kearns-Sayre syndrome, MELAS syndrome, and MERRF syndrome are…
mitochondiral myopathies
What is Leber’s Hereditary Optic Neuropathy?
Inherited mitochondrial disease
- Affect TCA, ETC, beta-oxidation FA’s
- Defect in NADH dehydrogenase (ETC)
Malonate inhibits
Succinate dehydrogenase
Niacin is vitamin ____
B3
Riboflavin is vitamin ______
B2
Thiamine is vitamin ____
B1
Pantothenate is another name for _____
coA
Cobalamin is vitamin ______
B12
Fluroacetate inhibits what in TCA cycle?
Acotinase
Arsenic poisoning affects this in the PDH
Results from its binding to lipoic acid which is needed for the activity of dihydrolipoyl transacetylase
What is Werneke-Korsakoff syndrome?
- Thiamine deficiency
- Ataxia, opthalmolplagia
- Memory loss
- Cerebral hemorrhage
- Common in alcoholics, malnourished individuals
Can result in: heart failure, decrease ATP, increased cardiac output
Other thiamine-requiring enzymes: alpha-ketogluterate DH & branched-chain alpha-ketoacid DH
What is congenital lactic acidosis (pyruvate dehydrogenase deficiency)
Metabolic: increase in pyruvate with concomitant increase in lactic acid and alanine; decrease production in acetyl coA; severe reduction in ATP production
* Loss of 30 ATP from PDH TCA!
Clinically: lactic acidosis, neuro defects, myopathy, usually fatal
What is the Warburg effect in cancer?
Most cancer cells use glycolysis as main source of ATP
- A glucose FDG (flurodeoxyglucose) is used for PET scanning
- Tumor cells take up FDG
- Pharm. Inhibitors of glycolysis explored as therapeutic agents
What is Leigh Disease?
Inherited pyruvate dehydrogenase deficiency
What is the most common glycolytic enzyme deficiency?
G-6-P deficiency
What results clinically secondary to pyruvate kinase deficiency?
Hemolytic anema
What results from inherited GK deficiency?
Rare form of inherited DM and elevated blood glucose
-Beta-cells of pancreas cannot respond to high blood glucose levels
Taking too many antacids can result in…
Reduction of protein digestion in the stomach b/c at an increased pH, the gastric HCl will not be active to denature protein
A high carbohydrate diet will lead to…
An increase in FA synthesis in the liver, increased fat deposits
What is autocatyltic pancreatitis?
Trypsin is abnormally active in the pancreas; it abnormally activates other pancreatic zymogens
highly active proteases and phospholipase A will destroy proteins and lipids in the membrane of the pancereas and at the pancreatic duct
- Etiology: gallstones/tumor (inc. ALP)
- Hyper TAGemia
- ETOH abuse
- Serum markers: amylase & lipase
What is cholelithiasis?
Cholesterol gallstone disease
- Can lead to pancreatitis
- Etiology: decreased bile salts and phosphatidylcholine in bil
- Increased biliary cholesterol secretion
What is steatorrhea and what does it result from?
Fatty feces
- Lack conjugated bile salts
- Defects in pancreatic juices
- Defective mucosa
- Short bowel syndrome
What is celiac disease?
Gluten intolerance
What are the 3 forms of lactose intolerance?
Congenital - can be serious (milk for the infants!!!)
Primary - Lactase activity down to 10%
Secondary - damage to intestinal mucosa
Describe cystic fibrosis.
Defective CFTR
1. Dec. reabsorption of sweat (salty sweat test)
2. Dec expulsion of Cl- in lungs/panc; mucous becomes very thick (water usually follows Cl-
Can lead to fibrosis of the pancreas, pulmonary fibrosis
In glycolysis, Fluoride inhibits this enzyme
Enolase
What is the overall objective of ETC/Oxidative phosphorylation?
Oxidize high energy NADH & FADH2
- Generate electrical potential by passing electrons to oxygen
- This gradient drives the phosphorylation of ADP to ATP
Where is a proton gradient established in ETC?
Inner mitochondrial membrane
Where does the ETC occur?
Inner mitochondrial membrane
Describe protein complexes I-IV & their respective prosthetic groups.
I: NADH dehydrogenase (FMN & FAD)
II: Succinate dehydrogenase (FMN & FAD)
III: Cytochrome reductase (Fe 3+ - heme)
IV: Cytochrome oxidase (Cu 2+ & Fe 3+)
Who oxidizes NADH, FADH2?
CoQ
Who oxidizes CoQ?
Cytochrome C at complex III
Who is the final acceptor of electrons?
Oxygen at complex IV
At which complexes are protons pumped into the intermembrane space of mitochondria?
I, III, IV
What are the components of complex V?
F0- channel/pore for H+ into the matrix
F1- enzyme capable of synthesizing ATP from ADP & Pi
Under what conditions is ETC active?
High: NADH:NAD+
High: ADP:ATP
Under what condition is ETC inactive?
Hypoxia
* Tissues are dependent on aerobic metabolism (particularly brain, heart)
The following inhibit what in the ETC?
- Rotenone
- Piericidin A
- Amytal
NADH dehydrogenase
- Rotenone - insecticide
- Piericidin A - antibiotic
- Amytal - barbituate
The following inhibit what in the ETC?
-Antimycin A
Complex III (cytochrome b of cytochrome reductase) - Antimycin - antibiotic
The following inhibit what in the ETC?
-Oligomycin
ATP Synthase (complex V) - Oligomycin - streptomyces antibiotic
The following inhibit what in the ETC?
- CO
- Azide
- H2S
- CN
Cytochrome oxidase (complex IV)
Effect of these two inhibitors of ETC is similar to what:
- Atractyloside
- Bongkrekic acid
Oligomycin
- toxic from plant - binds intermembrane space portion of adenine nucleotide transporter
- from contaminated coconuts - binds matrix portion of adenine nucleotide transporter
Differentiate between ETC inhibitors and decouplers with respect to ATP synthesis, ETC activity and O2 consumption.
Inhibitors – everything decreases
Decouplers – ETC & O2 consumption increases (ATP syn decreases)
What are the effects of DNP, ASA, thermogenin & ionophores on ETC?
Destroy the proton gradient (these are uncouplers)
Dissipation of the proton gradient generates heat. This uncoupler’s chief role is heat generation. What is it and where is it found?
Thermogenin (brown fat - neck & upper back – think newborns!)
What is another name for thermogenin and how is it activated?
UCP - uncoupling protein
* Activated w/ hormones which release FA’s from triglycerides in brown fat
What are uncouplers?
Compounds that increase the permeability of the inner mitochondrial membranr
What is gluconeogenesis?
Making glucose from non-carbohydrates and releasing it into the blood.
Where does glucneogenesis take place?
90% liver, 10% kidney (overnight fast)
Where does gluconeogenesis normally take place during a prolonged fast?
60% liver, 40% kidney
What stimulates gluconeogenesis?
Glucagon & cortisol
Why do we need gluconeogenesis?
Liver stores of glycogen can only take us so far
- Brain, RBC’s & renal medulla use a lot of ATP, and thus need glucose
Describe the “reversal of glycolysis”
Pyruvate –> oxaloacetate (malate-oxaloacetate) –> PEP
- Pyruvate carboxylase – requires biotin, acetyl coA and CO2 & ATP
- PEP carboxylase – requires 1 GTP
F-1,6 biphosphate –> F,6,phosphate (F-1,6, biphosphatase)
G-6-P –> glucose (glucose 6 phosphatase)
How is acetyl coA alternatively formed?
Beta-oxidation of fatty acids
What are substrates for gluconeogenesis?
Lactate (muscle + RBC), alanine, glutamine (protein degradation / urea), glycerol (fat),
What is the relationship between oxaloacetate and malate?
Oxo can’t leave the mitochondria; it is converted into malate, which enters the cytosol and is then re-converted to oxo
What will inhibit F-1,6 biphosphatase?
High AMP in the liver (this is bad!), will cause the liver to reserve energy for important processes
What inactivates pyruvate kinase?
Protein kinase A
High levels of acetyl coA will stimulate what and inhibit what?
Inhibit PDH
Stimulate pyruvate carboxylase
