Random other info Flashcards
glycogen supplements contain
- macro glycogenic nutrients
- micro intracellular ergogenic substrates
- most body can use to restore: 0.7 g/kg
- ‘recommended’ - 76 g
glycogen phosphorylase converts from
n residues –> n-1 residues + glucose-1-phosphate
phosphorylation of GP causes
- the amino terminus of the protein (res 10-22) to swing through 120 degrees, moving into the subunit interface and moving Ser-14 by more than 3.6 nm (CONFORMATIONAL CHANGE)
- 9 ser residues on GP are phosphorylated
for glycogen synthesis, how many residues are phosphorylated?
5 Ser residues on GS are phosphorylated
normal liver size for adult and 10 yo
adult liver: 2.2 kg (4.8 lbs)
10 yo liver: 1.2 kg (2.5 lbs) — becomes up to 7 lbs (10% bpdy weight in Von Gierke’s)
molecular defects in Glucose-6-phosphatase deficiency (and location)
(Von Gierkes)
Type 1a: absence of activity of catalytic subunit of glucose-6-Pase enzyme complex
Type 1b: glucose-6-Pase transport
Type 1c: microsomal phosphate or pyrophosphate transport
Type 1d: microsomal glucose transport
Syria and Lebanon- serious form of disease
Saudi Arabia- mild
Glucose-6-P can go to
- PPP –> synthesis of NADPH and 5-C sugars
- Fructose-6-P –> the rest of glycolysis
- Glucose-1-P –> Glycogen (energy storage in liver/muscle) or Glucuronate
The side products of PPP go to
the 2 NADPH go to reductive anabolic pathways (fatty acid synthesis)
how is NAD+ converted to NADP+?
via NAD+ kinase
only difference between NAD+ and NADP+ structurally is a PO4- added where one of the OH’s used to be
XK in PPP
may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis
D-xylulose –> xylulose-5-P via XK
important products/purposes of PPP
oxidative phase: NADPH to fatty acid synthesis
non-oxidative: ribose-5-P to nucleic acid biosynthesis (DNA/RNA), Fructose-6-P and glyceraldehyde-5-P as glycolytic intermediates
target for cancer therapy
- NADK
- Due to the essential role of NADPH in lipid and DNA biosynthesis and the hyper proliferative nature of most cancers, NADK is an attractive target for cancer therapy
Also:
- phosphatidic acid may act as a target model for novel anti-cancer drugs
- Nucleotide synthesis pathways are good targets for anti-cancer/antibacterial strategies
Gln PRPP amidotransferase:
- Site of action for Azaserine
- Antibiotic and anti-tumor agent
phosphatidylcholine
a complex membrane lipid
size of glycogenin
37 kDA homodimer
visceral fat linked to
metabolic disturbances and increased risk of CVD and T2D
- in women, breast cancer, the need for gallbladder surgery
excess fat stored in
lipocytes (which expand size until fat is used for fuel)
values of energy per unit weight of different energy sources:
fat: 37 kJ
protein: 17 kJ
glycogen: 16 kJ
glucose: 16 kJ
mass of different energy sources
fat: 15,000g (83%) of stored energy
protein: 6,000g
glycogen: 190g
glucose: 20g
essential fat% for men and women
men: 2-4%
women: 10-12%
acceptable fat % for women/men + obese fat%
acceptable:
- 25-31% for women
- 18-25% for men
obese:
- 32+% for women
- 25%+ for men
what do pancreatic lipases do?
break triacylglycerols down into diacylglycerols and monoacylglycerols
lipase enzymes
a diverse array of genetically-distinct lipase enzymes are found in nature and represent several types of protein folds and catalytic mechanisms
- most are built on an alpha/beta hydrolase fold and employ a mechanism using a catalytic triad consisting of a serine nucleophile, a histidine base, and an acid residue (usually Asp)
mixed micelles are made up of
long-chain fatty acids + bile salts
Knoop concluded that
phenyl products (phenyl acetate and benzoate) could only result from beta-oxidation if carbons were removed in pairs
what are the important side products of beta-oxidation and when are they produced?
NADH (produced in step that uses hydroxyacyl-CoA DH)
FADH2 (produced in step that uses acyl-coA DH)
reactions in beta-oxidation and where we’ve seen it before
oxidation -> hydration -> oxidation (first three)
(same as TCA)
note: fourth is reverse Claisen condensation that cleaves the beta-keto ester
reaction 1 of beta oxidation
fatty acyl-CoA –> trans-delta enoyl-CoA
enzyme: Acyl-CoA dehydrogenase
produces FADH2 from FAD
where does Acetyl-CoA come from (before entering Krebs)
breakdown of proteins, polysaccharides and FATS (to FAs)
connection between ETS + beta oxidation
FADH2 enters flavoprotein 3 which goes to UQ/UQH2 pool
ATP yield from beta oxidation for palmitic acid (C16)
- 8 acetyl-CoAs
- 7 NADH
- 7 FADH2
(106 ATP)
Beta-oxidation - oxidizing odd-carbon FA’s: the steps
propionyl coA -> D-Methylmalonyl-CoA –> L-Methylmalonyl-CoA –> Succinyl-CoA
Enzymes:
(1) Propionyl-CoA carboxylase
(2) Methylmalonyl-CoA epimerase (D-> L conversion)
(3) Methylmalonyl-CoA mutase (rearrangement)
For beta-oxidation – oxidizing odd carbon FAs, what are two coenzymes involved and which enzymes are they involved with?
biotin + B12
Biotin: propionyl-CoA carboxylase is biotin-dependent (the first enzyme that converts propionyl-CoA)
B12: Methylmalonyl-CoA mutase (the enzyme that converts to succinyl-CoA)
What is the enzyme number of Enoyl-CoA isomerase and what does it do?
EC 5.3.3.8
converts cis to trans-delta acyl CoA
Path of beta-oxidation for unsaturated FAs
three cycles of beta oxidation
-> cis-delta-dodeconyl-CoA ——-(ECI)—–> trans-delta-dodecenoyl-CoA —>
(now normal beta-oxidation)
trans-delta-dodecenoyl-CoA -> beta-hydroxyacyl-CoA (via enoylCoA hydratase)…..
Alcohol Dehydrogenase reactions
Ethanol (CH3CH2OH) —-> Acetaldehyde (CH3CHO) via ADH
Acetaldehyde —> Acetic acid (CH3COOH) via ALDH –> excreted
OR
Acetaldehyde –> GSH-adduct (via glutathione)
Acetaldehyde is TOXIC
Acute Cerebellar Ataxia Symptoms:
- impaired coordination in the torso or arms and legs
- frequent stumbling
- unsteady gait
- uncontrolled or repetitive eye movements
- trouble eating and performing fine motor tasks
- slurred speech
- vocal changes
- headaches
name one cis, one trans, and one saturated fat
oleic: cis
elaidic: trans
stearic: saturated
reaction of beta-oxidation (for palmitic acid)
CH3(CH2)14CO-CoA + 108 Pi + 23 O2 –> 108 ATP + 16 CO2 + 130 H2) + CoA
three ketone bodies
acetoacetate, acetone, beta-hydroxybutyrate
ketogenesis pathway
acetyl-CoA ———-(beta-ketothiolase)——> acetoacetyl-CoA —–(HMG-CoA synthase)—–> HMG-CoA ——–(HMG-CoA lyase)——-> acetoacetate —–> acetone and beta-hydroxybutyrate (the second one is via b-hydroxybutyrate DH)
HMG-CoA connection between paths
HMG-CoA is part of formation of ketone bodies from acetyl-CoA and also forms cholesterols via HMG-CoA reductase
FA synthesis pattern and how it relates to other processes we’ve seen
reduction- dehydration-reduction (opposite of beta-oxidation)
what coenzyme is involved in acetyl-CoA carboxylase reaction?
BIOTIN (because ACC uses bicarbonate, ATP)
Animal ACC enzyme
one polypeptide with all three functions: biotin carboxyl carrier, biotin carboxylase, transcacrboxylase
(E. coli enzyme has three separate units)
Bacteria/Plants: Domain 1 enzymes
Domain 1:
- beta-ketoacyl-ACP synthase
- malonyl transferase
enzymes are separate and in a complex
FA Synthase in animals: what happens in each domain?
FA synthase is a multi enzyme complex
Domain 1: acyl and malonyl binding and condensation
Domain 2: reduction of domain 1 intermediate
Domain 3: liberation of palmitate product
How does lipogenesis work?
- Excess glucose from the blood enters adipocyte –> TAG
- insulin
- VLDL and chylomicrons enter adipocytes –> fatty acids –> TAG
glucagon is associated with
low blood glucose
biosynthesis of glycogen
extracellular glucose -> intracellular glucose -> glucose-6-P -> glucose-1-P -> UDP-glucose -> short chain of glucose polymer ——–> glycogen
Lecithin/Sphingo (L/S) ratio for baby development
L:S ratio:
mature: >1.9 (PG present)
borderline: 1.5-1.9 (PG absent)
immature: <1.5 (PG absent)
mature (diabetic mothers): >3.4
Spiders
- Brown recluse venom, is cytotoxic/hemolytic.
- It contains hyaluronidase, deoxyribonuclease, ribonuclease, alkaline phosphatase, and lipase and sphingomyelinase D.
- Sphingomyelinase D responsible for most of the tissue destruction and hemolysis.
- The intense inflammatory response mediated by arachidonic acid, prostaglandins, and chemotactic infiltration of neutrophils
production of prostaglandins, thromboxjnes, prostacyclin
membrane phospholipids -> arachidonic acid
arachidonic acid –> prostaglandins, thromboxjnes (this is inhibited by NSAIDS)
arachidonic acid –> prostaglandins, prostacyclin (inhibited by NSAIDS, COX-2 inhibitors)
tetrahedral intermediate is key for
HMG-CoA reductase (in cholesterol biosynthesis)
pregnenolone is formed where? progesterone is formed where?
pregnenolone: formed in mitochondria
progesterone: formed in ERA
diseases associated with estrogen
- heart disease
- cancer (1/8 women, 85% survival in 5 years)
- stroke
- more
sources of omega 3, 6, 9
omega 3: essential FA
- DHA, EPA: fish
- ALA: flax seeds, chia seeds
omega 6: essential FA
- grape seed oil, sesame oil
omega 9: non-essential FA
- olive oil, canola oil
ki for mevinolinic acid (related to statins)
ki = 0.6 nM
side effects of colesevelam hydrochloride (cholestagel)
- constipation
- abdominal pain
- bloating
- vomiting
- diarrhea
- weight loss
- flatulence
lipoprotein density
highest density: HDL (also most protein compared to lipids)
lowers density: chylomicrons, VLDL
molecular weight of apolipoproteins
Apo A-1: 29,000
Apo B-100: 513,000
Apo C-II: 8800
Apo E: 34,000
LDL + LDL receptor interaction - key apoproteins
Apo B-100 and ApoE key in this interaction
- B-100 is embedded in surface of the LDL receptor
transaminations (for purine synthesis) - dependent on what coenzyme
pyrudixal phosphate
IMP Biosynthesis: Reaction 1
Enzyme: Ribose-5-P Pyrophosphokinase
- Ribose-5-P –> 5-Phosphoribosyl-pyrophosphate
IMP Biosynthesis: Reaction 2
Enzyme: Glutamine PRPP amidotransferase
5-PRPP –> Phosphorybosyl-beta-amine
Folic acid reduces risk of
cancer (colon, breast cancer), senility/Alzheimer’s
What is unique about Alcohol Dehydrogenase?
its Zn site (structural stability role)
name of the drug that inhibits ALDH
antabuse
what’s a process NADH is used for
fatty acid synthesis
what is inosine-5-P?
a purine nucleotide
Importance of DPA, EPA, DHA
- DPA is important factor for preventing CVD
- EPA is a huge factor in fighting inflammation
- DHA is an essential molecule for brain, nerve and eye tissues, and is a powerful factor for normalizing blood and tissue triglycerides
What does LP lipase do and what is it activated by?
LP lipase is activated by apoC-11. LP lipase hydrolyzes TAGs
Source of Nitrogen in plants and microorganisms
- In these organisms, glutamate is the source of N, via transamination (aminotransferase) reactions
