Ch. 12: CHO Metabolism I: Glycolysis & TCA Cyle Flashcards
What are the 2 purely ketogenic a.a.?
Leu
Lys
What is the common product all digestion products are metabolized to?
Acetyl-CoA
5 fates of glucose?
1) convert to glycogen
2) pentose phosphate pathway/HMP shunt
3) glycerol of TG
4) carbon skeleton for a.a.
5) acetyl CoA for FA & cholesterol synthesis
Which a.a. bypass liver and go to tissues?
3 branch-chained a.a.
How many ATP are gained aerobically?
36-38 ATP
How many ATP are gained anaerobically?
2 ATP
Glucose transporters: GLUT-1
Locations? Properties?
Brain, microvessels, RBCs, placenta, kidneys, other cells
Low Km, ubiquitous basal transporter
Defect of GLUT 1?
Poorly controlled seizures
Delayed development
Glucose transporters: GLUT-2
Locations? Properties?
Liver, pancreatic beta cells, small intestine
High Km
Release insulin
Glucose transporters: GLUT-3
Locations? Properties?
Brain, placenta, fetal muscle
Low Km
Provide glucose to glucose-dependent tissues
Glucose transporters: GLUT-4
Locations? Properties?
Skeletal & heart muscle, fat tissue
Insulin-responsive transporter (insulin causes glut 4 within cells to move to cell membrane)
Glucose transporters: GLUT-5
Locations? Properties?
Small intestine, testes
High affinity for fructose
Glucose transporters: SGLT 1 & 2
Locations? Properties?
Small intestines, renal tubules (SGLT 1) Renal tubules (SGLT 2)
Low Km
When will GLUT 2 activate? (Only)
Hyperglycemia
Insulin secretion: mechanism
⬆️ glu ➡️ ⬆️ATP ➡️ blocks ATP/K+ channel ➡️ membrane depolarization ➡️ ⬆️Ca2 ➡️ insulin secretion
ATP/K+ channel also blocked by sulphonlyurea
Glycolysis:
G3P dehydrogenase catalyzes what step?
What inhibits it?
Glyceraldehyde 3-phosphate ➡️ 1,3-bisphosphoglycerate
Iodoacetate
Glycolysis:
Enolase catalyzes what step?
What inhibits it?
2-phosphoglycerate ➡️ phosphoenolpyruvate
Fluoride
1st main regulatory point of glycolysis?
Positive modulators? Negative?
Hexokinase (glucose ➡️ glucose-6-phosphate)
➕: ATP, Pi
➖: glucose-6-phosphate
2nd main regulatory point of glycolysis?
Positive modulators? Negative?
6-phosphofructokinase (fructose-6-phosphate ➡️ fructose-1,6-bisphosphate)
➕: fructose-2,6-bisphosphate, ADP, AMP, Pi, K+, NH4+
➖: ATP, citrate
3rd main regulatory point of glycolysis?
Positive modulators? Negative?
Pyruvate kinase (phosphoenolpyruvate ➡️ pyruvate)
➕: fructose-1,6-bisphosphate
➖: ATP, acetyl-CoA, alanine
Compare Km & Vmax of glucokinase vs hexokinase
Glucokinase: ⬆️ Km, ⬆️ Vmax (only active w/hyperglycemia)
Hexokinase: ⬇️ Km, ⬇️ Vmax
Muscle: what is key enzyme of glycolysis? Regulation?
PFK1
Activated: AMP
Inhibited: ATP, citrate
Liver: what are the key enzymes of glycolysis?
Glucokinase
PFK1 (activated by F-2,6-P)
Pyruvate kinase
Where are hexokinase I, II, III found?
Where is hexokinase IV (glucokinase) found?
Extrahepatic tissue
Liver, pancreatic beta cells
Fxn of glucokinase: liver?
Hyperglycemia: ⬆️ glucokinase levels ➡️ initiates metabolism of glucose, maintain uptake of glucose into hepatocytes
Hypoglycemia: ⬇️ glucokinase levels ➡️ liver provider of glucose
Fxn of glucokinase: pancreas?
Glucose sensor
Modulates insulin secretion (ATP/K+ channel)
RBCs: 1,3-BPG converted to ? Fxn of this product?
2,3-BPG
Allosteric modulator of hemoglobin (R shift of O2 curve)
In what situation is pyruvate kinase inhibited in liver? Activated?
Phosphorylated in liver during fasting (⬆️ glucagon levels)
Fed state
4 major pathways of pyruvate metabolism?
1) ➡️ lactate (lactate dehydrogenase)
2) ➡️ acetyl CoA (pyruvate dehydrogenase complex)
3) ➡️ oxaloacetate (pyruvate carboxylase)
4) ➡️ alanine (alanine aminotransferase)
RBCs: what occurs during low O2?
deoxy-Hb binds to transmembrane protein band 3 ➡️ releases glycolysis enzymes ➡️ ATP synthesis
RBCs: what occurs during ⬆️ O2?
Glycolysis enzymes inactive ➡️ HMP shunt active ➡️ NADPH synthesis (antioxidant, reduces glutathione)
How does tissue hypoxia ➡️ lactic acidosis?
⬇️ O2 ➡️ ⬇️ ATP ➡️ NADH build-up ➡️ promotes conversion of pyruvate to L-lactate
When does D-lactate acidosis occur?
Jejunoileal bypass, bowel resection
More nutrients in colon ➡️ Gram + bacteria ferment glucose to D-lactate
What are the 2 shuttle systems for moving NADH from cytosol ➡️ mitochondria?
G3P shuttle (makes FADH2, 2 ATP)
Malate aspartate shuttle (makes NADH, 3 ATP)
What 3 enzymes make up the pyruvate dehydrogenase complex?
E1: pyruvate decarboxylase
E2: dihydrolipoyl transacetylase
E3: dihydrolipoyl dehydrogenase
What are the 5 co-factors of the pyruvate dehydrogenase complex?
TPP (thiamine pyrophosphate) lipoic acid FAD NAD+ CoA
PD kinase: inactivates PDH complex, how?
Activated by? Inactivated by?
Phosphorylates Ser of PDH
➕: ATP/ADP, NADH/NAD+, acetyl CoA/CoA
➖: pyruvate, dichloroacetate, Ca2+
Phospho-PDH phosphatase: reactivates PDH complex
Activated by?
⬆️ Ca2+
⬆️ Mg2+
Insulin
Impacts of thiamine deficiency?
Accumulation of pyruvate & lactate in blood and brain ➡️ impairs cardiovascular, nervous, & GI (needs steady ATP supply)
Treatments for abnormalities of PDH complex?
Ketogenic diets
Thiamine
Dichloroacetate
Diet with asp & glu (can bypass glycosis, converted to TCA intermediates)
Why are organic arsenicals & arsenite toxic to PDH complex?
Other enzyme it inhibits?
Binds to SH group of lipoic acid
Alpha-ketoglutarate dehydrogenase
What rxn does aconitase catalyze?
What inhibits it?
Citrate ➡️ [cis-aconitate] ➡️ isocitrate
Fluoroacetate
What amino acids can oxaloacetate be made from?
Asp
Asn (deamination ➡️ Asp)
Citrate synthase: Activators? Inhibitors?
➕: ADP
➖: ATP, NADH, Succinyl CoA, Fatty acyl CoA
Isocitrate dehydrogenase: Activators? Inhibitors?
➕: ADP, Ca2+
➖: NADH, ATP
Alpha-ketoglutarate dehydrogenase complex: Activators? Inhibitors?
➕: Ca2+
➖: ATP, GTP, NADH, Succinyl CoA
How much ATP produced in TCA cycle?
3 NADH = 9 ATP
1 FADH2 = 2 ATP
1 GTP = 1 ATP
12 ATP (per acetyl CoA)
